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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 in the Treatment of Postmenopausal Women With Osteoporosis; A 12-Month Extension to: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin-K Inhibitor) in the Treatment of Postmenopausal Women With Osteoporosis; A 24-Month Extension to: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of Odanacatib (MK-0822) in the Treatment of Postmenopausal Women With Osteoporosis; and A 5-Year Open-Label Extension to: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of Odanacatib (MK-0822) in the Treatment of Postmenopausal Women With Osteoporosis

Summary
EudraCT number	2005-001511-22
Trial protocol	SE DK GB
Global end of trial date	20 Jan 2016

Results information
Results version number	v2(current)
This version publication date	18 Jul 2018
First version publication date	04 Feb 2017
Other versions	v1
Version creation reason	Correction of full data set updating to be consistent with ClinicalTrials.gov record

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

0822-004

ISRCTN number

US NCT number

NCT00112437

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Jan 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Jan 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objectives of the study were: 1) To estimate the change from baseline (randomization in Protocol 004-02) in bone mineral density (BMD) at the lumbar spine at Years 8 and 10 with 50 mg of odanacatib once weekly in postmenopausal osteoporotic women previously treated for up to 5 years with odanacatib once weekly (in Protocols 004-02, 004-11, and 004-22); and 2) To assess the safety of treatment with odanacatib 50 mg once weekly for up to 10 years.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Jun 2005

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

Austria: 24

Country: Number of subjects enrolled

Chile: 15

Country: Number of subjects enrolled

Colombia: 22

Country: Number of subjects enrolled

Denmark: 24

Country: Number of subjects enrolled

France: 18

Country: Number of subjects enrolled

Mexico: 19

Country: Number of subjects enrolled

New Zealand: 28

Country: Number of subjects enrolled

Norway: 30

Country: Number of subjects enrolled

Peru: 20

Country: Number of subjects enrolled

Sweden: 20

Country: Number of subjects enrolled

Switzerland: 17

Country: Number of subjects enrolled

United Kingdom: 15

Country: Number of subjects enrolled

United States: 132

Worldwide total number of subjects

399

EEA total number of subjects

131

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

223

From 65 to 84 years

174

85 years and over

Subject disposition

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Recruitment details

Approximately 375 participants were recruited from June 2005 to December 2005. Investigators used one or more of the following recruitment methods: Investigator Patient/Subject Database or Medical Records, Investigator's Local Recruitment/Advertising, Other Health Professional and, Physician Referral (Primary/Specialist/Family Doctor).

Screening details

Participants entered screening followed by a 3-week placebo run-in. All took vitamin D3, 5600 IU once weekly, those with average daily calcium intakes <1000 mg took calcium 500 mg/day as calcium carbonate. Participants were excluded from active treatment based on predetermined exclusion criteria (BMD and laboratory results).

Period 1 title

YEAR 1 (12-Month Base Study)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo-Base

Arm description

One placebo tablet once a week

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 3 mg-Base

Arm description

One odanacatib 3 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 3 mg tablet once a week

Odanacatib 10 mg-Base

Arm description

One odanacatib 10 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 10 mg tablet once a week

Odanacatib 25 mg-Base

Arm description

One odanacatib 25 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 25 mg tablet once a week

Odanacatib 50 mg-Base

Arm description

One odanacatib 50 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Number of subjects in period 1	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Started	83	82	77	79	78
Completed	68	64	65	71	66
Not completed	15	18	12	8	12
Consent withdrawn by subject	5	5	2	1	7
Adverse event, non-fatal	9	10	6	4	3
DXA was lower by more than 8%	-	-	-	-	1
Lost to follow-up	-	1	-	-	-
Moved	-	1	1	-	-
patient was unsure that they needed drug	-	-	-	2	-
Protocol deviation	1	-	3	1	1
Lack of efficacy	-	1	-	-	-

Period 2 title

YEAR 2 (12-Month Extension)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo-Ext 1

Arm description

One placebo tablet once a week

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 3 mg-Ext 1

Arm description

One odanacatib 3 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 3 mg tablet once a week

Odanacatib 10 mg-Ext 1

Arm description

One odanacatib 10 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 10 mg tablet once a week

Odanacatib 25 mg-Ext 1

Arm description

One odanacatib 25 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 25 mg tablet once a week

Odanacatib 50 mg-Ext 1

Arm description

One odanacatib 50 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Number of subjects in period 2 ^[1]	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Started	63	62	63	69	63
Completed	60	53	55	62	50
Not completed	3	9	8	7	13
Consent withdrawn by subject	1	1	2	4	1
Adverse event, non-fatal	1	2	6	1	7
Patient stopped taking medication	-	-	-	-	1
patient was out of windows	-	-	-	-	1
Lost to follow-up	-	-	-	1	-
Moved	-	-	-	-	1
Lack of efficacy	1	6	-	-	2
Protocol deviation	-	-	-	1	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed the preceding period entered this extension.

Period 3 title

YEAR 3 (12-Month Extension)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo/Placebo-Ext 2

Arm description

During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Placebo/Odanacatib 50 mg-Ext 2

Arm description

During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Odanacatib 3 mg/Placebo-Ext 2

Arm description

During this 12-month extension (Year 3), participants took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 3 mg/Odanacatib 50 mg-Ext 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Odanacatib 10 mg/Placebo-Ext 2

Arm description

During this 12-month extension (Year 3), participants took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 10 mg/Odanacatib 50 mg-Ext 2

Arm description

During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Odanacatib 25 mg/Placebo-Ext 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 25 mg/Odanacatib 50 mg-Ext 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Odanacatib 50 mg/Placebo-Ext 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Arm description

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Number of subjects in period 3 ^[2]	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Started	19	22	18	17	18	17	19	21	18	20
Completed	17	17	18	16	17	13	16	20	16	19
Not completed	2	5	0	1	1	4	3	1	2	1
Consent withdrawn by subject	-	3	-	-	1	-	-	-	-	-
Adverse event, non-fatal	1	-	-	-	-	1	3	1	-	1
Lost to follow-up	-	-	-	-	-	1	-	-	-	-
cortisone therapy, upcoming surgery	1	1	-	-	-	-	-	-	-	-
Lack of efficacy	-	1	-	1	-	1	-	-	2	-
Protocol deviation	-	-	-	-	-	1	-	-	-	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed the preceding period entered this extension.

Period 4 title

YEARS 4-5 (24-Month Extension)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Placebo once weekly

Arm description

One placebo tablet once a week

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One placebo tablet once a week

Odanacatib 50 mg once weekly

Arm description

One odanacatib 50 mg tablet once a week

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Number of subjects in period 4 ^[3]	Placebo once weekly	Odanacatib 50 mg once weekly
Started	41	100
Completed	37	92
Not completed	4	8
Participant moved	-	1
Consent withdrawn by subject	1	2
Adverse event, non-fatal	-	4
Participant discontinued for other reason	1	-
Lack of efficacy	2	1

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed the preceding period entered this extension.

Period 5 title

YEARS 6-10 (60-Month Extension)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group A: Odanacatib 50 mg once weekly

Arm description

Group A consists of a combination of participants who were treated with odanacatib 25 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Group B: Odanacatib 50 mg once weekly

Arm description

Group B consists of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Group C: Odanacatib 50 mg once weekly

Arm description

Group C consists of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Group D: Odanacatib 50 mg once weekly

Arm description

Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participents who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.

Arm type

Experimental

Investigational medicinal product name

Odanacatib

Investigational medicinal product code

MK-0822

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One 50 mg tablet once a week

Number of subjects in period 5 ^[4]	Group A: Odanacatib 50 mg once weekly	Group B: Odanacatib 50 mg once weekly	Group C: Odanacatib 50 mg once weekly	Group D: Odanacatib 50 mg once weekly
Started	28	34	23	32
Completed	23	22	22	27
Not completed	5	12	1	5
Physician decision	-	2	-	-
Adverse event, non-fatal	1	2	-	1
Death	-	2	-	-
Other	-	-	1	-
Lost to follow-up	-	-	-	1
Withdrawal by subject	4	6	-	3

Notes
[4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed the preceding period entered this extension.

Baseline characteristics

Top of page

Reporting group title

Placebo-Base

Reporting group description

One placebo tablet once a week

Reporting group title

Odanacatib 3 mg-Base

Reporting group description

One odanacatib 3 mg tablet once a week

Reporting group title

Odanacatib 10 mg-Base

Reporting group description

One odanacatib 10 mg tablet once a week

Reporting group title

Odanacatib 25 mg-Base

Reporting group description

One odanacatib 25 mg tablet once a week

Reporting group title

Odanacatib 50 mg-Base

Reporting group description

One odanacatib 50 mg tablet once a week

Reporting group values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base	Total
Number of subjects	83	82	77	79	78	399
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	65.9 ( 7.8 )	63.1 ( 7.3 )	64.5 ( 8 )	62.9 ( 7.4 )	64.5 ( 8.1 )	-
Gender categorical
Units: Subjects
Female	83	82	77	79	78	399
Male	0	0	0	0	0	0

End points

Top of page

Reporting group title

Placebo-Base

Reporting group description

One placebo tablet once a week

Reporting group title

Odanacatib 3 mg-Base

Reporting group description

One odanacatib 3 mg tablet once a week

Reporting group title

Odanacatib 10 mg-Base

Reporting group description

One odanacatib 10 mg tablet once a week

Reporting group title

Odanacatib 25 mg-Base

Reporting group description

One odanacatib 25 mg tablet once a week

Reporting group title

Odanacatib 50 mg-Base

Reporting group description

One odanacatib 50 mg tablet once a week

Reporting group title

Placebo-Ext 1

Reporting group description

One placebo tablet once a week

Reporting group title

Odanacatib 3 mg-Ext 1

Reporting group description

One odanacatib 3 mg tablet once a week

Reporting group title

Odanacatib 10 mg-Ext 1

Reporting group description

One odanacatib 10 mg tablet once a week

Reporting group title

Odanacatib 25 mg-Ext 1

Reporting group description

One odanacatib 25 mg tablet once a week

Reporting group title

Odanacatib 50 mg-Ext 1

Reporting group description

One odanacatib 50 mg tablet once a week

Reporting group title

Placebo/Placebo-Ext 2

Reporting group description

Reporting group title

Placebo/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Odanacatib 3 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Odanacatib 3 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Odanacatib 10 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Odanacatib 10 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Odanacatib 25 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Odanacatib 25 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Odanacatib 50 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Placebo once weekly

Reporting group description

One placebo tablet once a week

Reporting group title

Odanacatib 50 mg once weekly

Reporting group description

One odanacatib 50 mg tablet once a week

Reporting group title

Group A: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Group B: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Group C: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Group D: Odanacatib 50 mg once weekly

Reporting group description

Primary: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

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End point title

Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

End point description

Percentage change in lumbar spine BMD (relative to baseline) at 12 months. Analysis at Month 12 used Full-Analysis-Set (FAS) Population of patients who took at least one dose of study medication and had necessary follow-up information, in their randomization treatment group, with last observation data carried forward. Seven patients had a baseline value, but no value at Month 12 for lumbar spine BMD.

End point type

Primary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	81	79	77	78	77
Units: Percent Change
least squares mean (confidence interval 95%)	-0.13 (-0.8 to 0.54)	-0.62 (-1.3 to 0.05)	1.5 (0.82 to 2.19)	2.65 (1.97 to 3.33)	3.37 (2.68 to 4.05)

Difference in Least Squares Means

Statistical analysis description

The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Lumbar Spine BMD compared to placebo over 12 months. The primary hypothesis states that odanacatib will increase Lumbar Spine BMD compared to placebo over 12 months.

Comparison groups

Odanacatib 50 mg-Base v Placebo-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[1]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.54

upper limit

4.45

Notes
[1] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[2]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.82

upper limit

3.73

Notes
[2] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.003 ^[3]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

2.59

Notes
[3] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.343 ^[4]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-1.44

upper limit

0.46

Notes
[4] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 24 Months

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End point title

Percentage Change From Baseline in Lumbar Spine BMD at 24 Months

End point description

Percentage change in lumbar spine BMD (relative to baseline) at 24 months. Analysis on lumbar spine BMD (g/cm2) at Month 24 used the FAS Population with Last Observation Carried Forward from Month 18 to 24. No data were carried forward from the core to the extension period. Only patients who took at least one dose of extension medication were included. 17 patients were excluded from FAS.

End point type

Primary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	62	58	60	65	58
Units: Percent Change
least squares mean (confidence interval 95%)	-0.19 (-1.13 to 0.75)	-1.03 (-2 to -0.07)	3.2 (2.25 to 4.15)	4.26 (3.35 to 5.18)	5.48 (4.52 to 6.44)

Difference in Least Squares Means

Statistical analysis description

The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Lumbar Spine BMD compared to placebo over 24 months. The primary hypothesis states that odanacatib will increase Lumbar Spine BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[5]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

5.67

Confidence interval

level

95%

sides

2-sided

lower limit

4.32

upper limit

7.02

Notes
[5] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[6]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

4.45

Confidence interval

level

95%

sides

2-sided

lower limit

3.15

upper limit

5.76

Notes
[6] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[7]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

3.39

Confidence interval

level

95%

sides

2-sided

lower limit

2.06

upper limit

4.73

Notes
[7] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.218 ^[8]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-2.19

upper limit

0.51

Notes
[8] - Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 36 Months

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End point title

Percentage Change From Baseline in Lumbar Spine BMD at 36 Months

End point description

Percentage change in lumbar spine BMD (relative to baseline) at 36 months. This analysis was performed at Month 36 using the Per Protocol (PP) Population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Primary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	17	13	12	10	12	18	15	17
Units: Percent Change
least squares mean (confidence interval 95%)	0.42 (-1.89 to 2.73)	2.95 (0.79 to 5.11)	-1.57 (-3.67 to 0.54)	4.41 (2.01 to 6.82)	2.03 (-0.47 to 4.53)	6.11 (3.37 to 8.85)	0.32 (-2.18 to 2.82)	7.45 (5.41 to 9.48)	1.39 (-0.84 to 3.63)	7.85 (5.74 to 9.95)

Difference in Least Squares Means

Statistical analysis description

In postmenopausal women with osteoporosis assess the time course of resolution of effect on Lumbar Spine BMD during the 12 month extension following 24 months of treatment with odanacatib once weekly. The primary objective was to assess the resolution of effect, on lumbar spine BMD, for the patients who received odanacatib 50 mg for 3 years compared to those who received odanacatib 50 mg in the 2 year base period and switched to placebo for the 3rd year extension.

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

6.45

Confidence interval

level

95%

sides

2-sided

lower limit

3.38

upper limit

9.53

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months

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End point title

Percentage Change From Baseline in Lumbar Spine BMD at 60 Months ^[9]

End point description

Percentage change from baseline in lumbar spine BMD at 60 months. This analysis was based on the Full-Analysis Set (FAS) population, last observation carried forward. All patients who took at least one dose of base study medication were included in the base study time points, while for the extension study time points only patients who took at least one dose of extension medication were included. Missing values were imputed using the last observation-carried-forward principle for the FAS approach.

End point type

Primary

End point timeframe

Baseline and 60 months

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for the endpoint: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months

End point values	Placebo once weekly	Odanacatib 50 mg once weekly
Number of subjects analysed	14	13
Units: Percent change
arithmetic mean (confidence interval 95%)	-0.41 (-3.1 to 2.28)	11.88 (7.23 to 16.54)

No statistical analyses for this end point

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 120 Months

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End point title

Percentage Change From Baseline in Lumbar Spine BMD at 120 Months ^[10]

End point description

Percentage change from baseline in lumbar spine BMD at 120 Months. This analysis was based on the FAS population, which included all randomized participants who took at least 1 dose of extension study drug and had the necessary extension data available for this endpoint. Missing data were not imputed.

End point type

Primary

End point timeframe

Baseline and 120 months

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for the endpoint: Percentage Change From Baseline in Lumbar Spine BMD at 120 Months.

End point values	Group A: Odanacatib 50 mg once weekly	Group B: Odanacatib 50 mg once weekly	Group C: Odanacatib 50 mg once weekly	Group D: Odanacatib 50 mg once weekly
Number of subjects analysed	20	16	17	21
Units: Percent change
arithmetic mean (confidence interval 95%)	16.92 (12.28 to 21.55)	14.56 (11.1 to 18.02)	17.18 (11.48 to 22.88)	7.71 (4.46 to 10.95)

No statistical analyses for this end point

Primary: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)

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End point title

Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) ^[11]

End point description

Number of participants who experienced at least one adverse event (AE) during treatment years 6-10 (60 months). An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. This endpoint was based on the All Participants As Treated (APaT) population, consisting of all participants who received at least 1 administration of the trial drug during treatment years 6-10.

End point type

Primary

End point timeframe

Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for the endpoint: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months).

End point values	Group A: Odanacatib 50 mg once weekly	Group B: Odanacatib 50 mg once weekly	Group C: Odanacatib 50 mg once weekly	Group D: Odanacatib 50 mg once weekly
Number of subjects analysed	28	34	23	32
Units: Participants	27	34	23	32

No statistical analyses for this end point

Primary: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)

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End point title

Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) ^[12]

End point description

Number of participants who discontinued study treatment drug due to an AE during treatment years 6-10 (60 months) An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. This endpoint was based on the APaT population, consisting of all participants who received at least 1 administration of the trial drug during treatment years 6-10.

End point type

Primary

End point timeframe

Years 6-10 (up to 60 months)

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for the endpoint: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)

End point values	Group A: Odanacatib 50 mg once weekly	Group B: Odanacatib 50 mg once weekly	Group C: Odanacatib 50 mg once weekly	Group D: Odanacatib 50 mg once weekly
Number of subjects analysed	28	34	23	32
Units: Participants	1	2	0	1

No statistical analyses for this end point

Secondary: Percentage Change From Baseline in Total Hip BMD at 12 Months

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End point title

Percentage Change From Baseline in Total Hip BMD at 12 Months

End point description

Percentage change in total hip BMD (relative to baseline) at 12 months. This analysis was performed at Month 12 using FAS population with Last Observation Carried Forward.

End point type

Secondary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	81	79	77	78	77
Units: Percent Change
least squares mean (confidence interval 95%)	-0.61 (-1.22 to -0.01)	-1.36 (-1.97 to -0.75)	1.05 (0.44 to 1.67)	1.45 (0.84 to 2.07)	1.87 (1.25 to 2.49)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Hip BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase Total Hip BMD compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[13]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.49

Confidence interval

level

95%

sides

2-sided

lower limit

1.62

upper limit

3.35

Notes
[13] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[14]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.06

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

2.93

Notes
[14] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[15]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

2.53

Notes
[15] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.135 ^[16]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.75

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

0.11

Notes
[16] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 12 Months

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End point title

Percentage Change From Baseline in Femoral Neck BMD at 12 Months

End point description

Percentage change in femoral neck BMD (relative to baseline) at 12 months. This analysis was performed at Month 12 using FAS population with Last Observation Carried Forward.

End point type

Secondary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	81	79	77	78	77
Units: Percentage change
least squares mean (confidence interval 95%)	-0.13 (-0.79 to 0.54)	-0.32 (-0.99 to 0.35)	0.74 (0.05 to 1.42)	1.76 (1.08 to 2.44)	2.53 (1.85 to 3.21)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

P-value

≤ 0.001 ^[17]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.66

Confidence interval

level

95%

sides

2-sided

lower limit

1.71

upper limit

3.61

Notes
[17] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[18]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

2.84

Notes
[18] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.095 ^[19]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

1.82

Notes
[19] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

0.75

Secondary: Percentage Change From Baseline in Trochanter BMD at 12 Months

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End point title

Percentage Change From Baseline in Trochanter BMD at 12 Months

End point description

Percentage change in trochanter BMD (relative to baseline) at 12 months. This analysis was performed at Month 12 using FAS population with Last Observation Carried Forward.

End point type

Secondary

End point timeframe

Baseline and 12 Months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	81	79	77	78	77
Units: Percentage change
least squares mean (confidence interval 95%)	-0.73 (-1.64 to 0.18)	-1.02 (-1.94 to -0.1)	1.65 (0.72 to 2.58)	1.91 (0.99 to 2.84)	2.21 (1.28 to 3.14)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[20]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.64

upper limit

4.24

Notes
[20] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[21]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

3.94

Notes
[21] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[22]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

3.69

Notes
[22] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.731 ^[23]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.58

upper limit

Notes
[23] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Secondary: Percentage Change From Baseline in Total Body BMD at 12 Months

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End point title

Percentage Change From Baseline in Total Body BMD at 12 Months

End point description

Percentage change in total body BMD (relative to baseline) at 12 months. This analysis was performed at Month 12 using the FAS population with Last Observation Carried Forward.

End point type

Secondary

End point timeframe

Baseline and 12 Months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	72	71	70	75	70
Units: Percentage change
least squares mean (confidence interval 95%)	-0.42 (-1.16 to 0.32)	-1.89 (-2.64 to -1.14)	-1.06 (-1.81 to -0.3)	-0.51 (-1.23 to 0.22)	-0.13 (-0.89 to 0.62)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total body BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total body BMD compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.112 ^[24]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

1.35

Notes
[24] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

0.95

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.69

upper limit

0.42

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.47

Confidence interval

level

95%

sides

2-sided

lower limit

-2.53

upper limit

-0.42

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 12 Months

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End point title

Percentage Change From Baseline in Distal Forearm BMD at 12 Months

End point description

Percentage change in distal forearm BMD (relative to baseline) at 12 months. This analysis was performed at Month 12 using the FAS population with Last Observation Carried Forward.

End point type

Secondary

End point timeframe

Baseline and 12 Months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	81	79	77	78	77
Units: Percentage change
least squares mean (confidence interval 95%)	-1.27 (-1.98 to -0.57)	-2.55 (-3.26 to -1.83)	-1 (-1.73 to -0.28)	-0.17 (-0.89 to 0.55)	-0.04 (-0.77 to 0.68)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on distal forearm BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase distal forearm BMD compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[25]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

2.24

Notes
[25] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005 ^[26]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

2.11

Notes
[26] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.63 ^[27]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

1.29

Notes
[27] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.27

Confidence interval

level

95%

sides

2-sided

lower limit

-2.28

upper limit

-0.27

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 12 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 12 Months

End point description

Back-transformation (geometric mean) of the least squares (LS) mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (u-NTx) at 12 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP population approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 12 Months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	62	57	56	63	56
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-2.37 (-14.78 to 11.85)	8.8 (-5.5 to 25.27)	-34.21 (-42.94 to -24.15)	-48.29 (-54.8 to -40.84)	-60.23 (-65.51 to -54.13)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[28]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-57.86

Confidence interval

level

95%

sides

2-sided

lower limit

-72.33

upper limit

-43.38

Notes
[28] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[29]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-45.92

Confidence interval

level

95%

sides

2-sided

lower limit

-60.93

upper limit

-30.91

Notes
[29] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[30]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-31.84

Confidence interval

level

95%

sides

2-sided

lower limit

-48.11

upper limit

-15.58

Notes
[30] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.249 ^[31]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

11.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

43.24

Notes
[31] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 12 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 12 Months

End point description

Back-transformation (geometric mean) of the least squares (LS) mean of the log-values percentage change from baseline in biochemical marker of bone turnover (s-CTx) at 12 Months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP population approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 12 Months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	62	57	56	62	55
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-0.58 (-16.79 to 18.78)	19.12 (-0.94 to 43.24)	-22.24 (-35.45 to -6.32)	-36.15 (-46.54 to -23.75)	-56.91 (-64.31 to -47.99)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[32]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-56.33

Confidence interval

level

95%

sides

2-sided

lower limit

-75.86

upper limit

-36.81

Notes
[32] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[33]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-35.57

Confidence interval

level

95%

sides

2-sided

lower limit

-56.63

upper limit

-14.51

Notes
[33] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.08 ^[34]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-21.66

Confidence interval

level

95%

sides

2-sided

lower limit

-44.54

upper limit

1.23

Notes
[34] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

19.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.48

upper limit

47.88

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values Percentage change in niochemical marker of bone turnover (u-DPyr) (relative to baseline) at 12 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using a PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP population approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	60	57	55	63	55
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-7.25 (-19.73 to 7.18)	20.91 (4.33 to 40.12)	-8.58 (-21.33 to 6.24)	-8.5 (-20.52 to 5.33)	-25.52 (-35.93 to -13.43)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004 ^[35]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-18.28

Confidence interval

level

95%

sides

2-sided

lower limit

-35.82

upper limit

-0.74

Notes
[35] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.344 ^[36]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-19.9

upper limit

17.39

Notes
[36] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.33

Confidence interval

level

95%

sides

2-sided

lower limit

-20.55

upper limit

17.89

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

28.15

Confidence interval

level

95%

sides

2-sided

lower limit

5.84

upper limit

50.46

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (s-BSAP), at 12 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP population approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	62	58	57	64	58
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-2.77 (-10.39 to 5.49)	42.08 (30.64 to 54.52)	8.95 (0.1 to 18.6)	2.66 (-5.25 to 11.24)	-18.35 (-24.93 to -11.18)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[37]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-15.57

Confidence interval

level

95%

sides

2-sided

lower limit

-26.11

upper limit

-5.04

Notes
[37] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.645 ^[38]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

5.43

Confidence interval

level

95%

sides

2-sided

lower limit

-6.02

upper limit

16.89

Notes
[38] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

11.73

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

23.92

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

44.85

Confidence interval

level

95%

sides

2-sided

lower limit

30.55

upper limit

59.16

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months

Top of page

End point title

Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change in biochemical marker of bone turnover (s-P1NP) (relative to baseline) at 12 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP population approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 12 months

End point values	Placebo-Base	Odanacatib 3 mg-Base	Odanacatib 10 mg-Base	Odanacatib 25 mg-Base	Odanacatib 50 mg-Base
Number of subjects analysed	62	57	57	63	58
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	3.91 (-8.79 to 18.38)	50.81 (31.69 to 72.7)	2.33 (-10.63 to 17.16)	2.23 (-10.12 to 16.28)	-31.83 (-40.4 to -22.02)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 12 months.

Comparison groups

Placebo-Base v Odanacatib 50 mg-Base

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[39]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-35.74

Confidence interval

level

95%

sides

2-sided

lower limit

-52.14

upper limit

-19.33

Notes
[39] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 25 mg-Base

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.161 ^[40]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-20.58

upper limit

17.23

Notes
[40] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 10 mg-Base

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.58

Confidence interval

level

95%

sides

2-sided

lower limit

-20.99

upper limit

17.82

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Base v Odanacatib 3 mg-Base

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

46.9

Confidence interval

level

95%

sides

2-sided

lower limit

22.35

upper limit

71.44

Secondary: Percentage Change From Baseline in Total Hip BMD at 24 Months

Top of page

End point title

Percentage Change From Baseline in Total Hip BMD at 24 Months

End point description

Percentage change in total hip BMD (relative to baseline) at 24 months. This analysis was performed at Month 24 using FAS Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	61	57	59	65	58
Units: Percentage change
least squares mean (confidence interval 95%)	-0.93 (-1.86 to -0.01)	-1.44 (-2.4 to -0.48)	1.82 (0.88 to 2.76)	2.55 (1.66 to 3.44)	3.16 (2.22 to 4.11)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Hip BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Hip BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[41]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.77

upper limit

5.42

Notes
[41] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[42]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

3.48

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

4.77

Notes
[42] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[43]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.43

upper limit

4.07

Notes
[43] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.536 ^[44]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

0.83

Notes
[44] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 24 Months

Top of page

End point title

Percentage Change From Baseline in Femoral Neck BMD at 24 Months

End point description

Percentage change in femoral neck BMD (relative to baseline) at 24 months. This analysis was performed at Month 24 using FAS Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	61	57	59	65	58
Units: Percentage change
least squares mean (confidence interval 95%)	-0.85 (-1.85 to 0.16)	-1.25 (-2.29 to -0.22)	1.97 (0.95 to 2.98)	2.73 (1.76 to 3.69)	3.84 (2.82 to 4.86)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Femoral Neck BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Femoral Neck BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[45]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

4.69

Confidence interval

level

95%

sides

2-sided

lower limit

3.25

upper limit

6.12

Notes
[45] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[46]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

3.57

Confidence interval

level

95%

sides

2-sided

lower limit

2.18

upper limit

4.97

Notes
[46] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[47]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

4.25

Notes
[47] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.585 ^[48]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

1.04

Notes
[48] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure

Secondary: Percentage Change From Baseline in Tronchanter BMD at 24 Months

Top of page

End point title

Percentage Change From Baseline in Tronchanter BMD at 24 Months

End point description

Percentage change in trochanter BMD (relative to baseline) at 24 months. This analysis was performed at Month 24 using FAS Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	61	57	59	65	58
Units: Percent Change
least squares mean (confidence interval 95%)	-0.81 (-2.15 to 0.53)	-0.85 (-2.23 to 0.53)	3.61 (2.26 to 4.97)	3.75 (2.46 to 5.04)	4.28 (2.92 to 5.65)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Trochanter BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Trochanter BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[49]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

5.09

Confidence interval

level

95%

sides

2-sided

lower limit

3.18

upper limit

7.01

Notes
[49] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[50]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

4.56

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

6.42

Notes
[50] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[51]

Method

ANCOVA

Parameter type

Difference in Least Square Means

Point estimate

4.43

Confidence interval

level

95%

sides

2-sided

lower limit

2.52

upper limit

6.33

Notes
[51] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.981 ^[52]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-1.97

upper limit

1.89

Notes
[52] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Secondary: Percentage Change From Baseline in Total Body BMD at 24 Months

Top of page

End point title

Percentage Change From Baseline in Total Body BMD at 24 Months

End point description

Percentage change in total body BMD (relative to baseline) at 24 months. This analysis was performed at Month 24 using FAS Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	56	47	48	58	51
Units: Percentage change
least squares mean (confidence interval 95%)	-1.54 (-2.42 to -0.66)	-2.7 (-3.66 to -1.74)	-1.35 (-2.29 to -0.4)	-0.43 (-1.29 to 0.43)	0.19 (-0.73 to 1.11)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Body BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Body BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[53]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

3.01

Notes
[53] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.028 ^[54]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

2.34

Notes
[54] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.804 ^[55]

Method

ANCOVA

Parameter type

Difference in Least Square Means

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.49

Notes
[55] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2.46

upper limit

0.15

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 24 Months

Top of page

End point title

Percentage Change From Baseline in Distal Forearm BMD at 24 Months

End point description

Percentage change in distal forearm BMD (relative to baseline) at 24 months. This analysis was performed at Month 24 using FAS Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	61	58	60	65	57
Units: Percentage change
least squares mean (confidence interval 95%)	-2.75 (-3.83 to -1.66)	-5.7 (-6.8 to -4.59)	-1.22 (-2.31 to -0.13)	-0.65 (-1.7 to 0.39)	0.15 (-0.97 to 1.27)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Distal Forearm BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[56]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

4.46

Notes
[56] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that MK0822 will increase Distal Forearm BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[57]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

3.6

Notes
[57] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that MK0822 will increase Distal Forearm BMD compared to placebo over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.094 ^[58]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

3.07

Notes
[58] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-2.95

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

-1.4

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 24 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 24 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (u- NTx) (relative to baseline) at 24 months Analysis used a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP protocol population did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	56	45	41	51	38
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-4.62 (-18.23 to 11.25)	12.89 (-4.93 to 34.05)	-40.57 (-50.32 to -28.9)	-38.3 (-47.48 to -27.51)	-51.83 (-60.05 to -41.91)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[59]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-47.21

Confidence interval

level

95%

sides

2-sided

lower limit

-64.51

upper limit

-29.9

Notes
[59] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[60]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-33.67

Confidence interval

level

95%

sides

2-sided

lower limit

-51.44

upper limit

-15.91

Notes
[60] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[61]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-35.94

Confidence interval

level

95%

sides

2-sided

lower limit

-54.15

upper limit

-17.74

Notes
[61] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.101 ^[62]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

17.51

Confidence interval

level

95%

sides

2-sided

lower limit

-6.78

upper limit

41.8

Notes
[62] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handle by Hochberg procedure.

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 24 Months

Top of page

End point title

Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 24 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (s-CTx)) (relative to baseline) at 24 months. Analysis used a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP protocol population did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	56	45	42	52	39
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	32.77 (13.28 to 55.61)	54.94 (29.83 to 84.92)	8.79 (-9.35 to 30.57)	-6.52 (-20.7 to 10.19)	-30.57 (-42.6 to -16.2)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[63]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-63.34

Confidence interval

level

95%

sides

2-sided

lower limit

-88.32

upper limit

-38.36

Notes
[63] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

other

P-value

≤ 0.001 ^[64]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-39.29

Confidence interval

level

95%

sides

2-sided

lower limit

-65.4

upper limit

-13.18

Notes
[64] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.124 ^[65]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-23.98

Confidence interval

level

95%

sides

2-sided

lower limit

-53.04

upper limit

5.09

Notes
[65] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

22.18

Confidence interval

level

95%

sides

2-sided

lower limit

-12.38

upper limit

56.73

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (u-DPyr) (relative to baseline) at 24 months. Analysis used geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP protocol population did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	56	45	40	51	38
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	-5.78 (-18.44 to 8.84)	15.96 (-1.29 to 36.23)	-7.57 (-22.03 to 9.57)	-14.3 (-26.3 to -0.33)	-22.49 (-34.96 to -7.64)

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.015 ^[66]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-16.71

Confidence interval

level

95%

sides

2-sided

lower limit

-36.03

upper limit

2.61

Notes
[66] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.246 ^[67]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-8.51

Confidence interval

level

95%

sides

2-sided

lower limit

-27.31

upper limit

10.29

Notes
[67] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-22.66

upper limit

19.08

Difference in Least Squares Means

Statistical analysis description

The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

21.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.32

upper limit

44.81

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (s-BSAP) (relative to baseline) at 24 months. Analysis used a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP protocol population did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	57	47	42	53	42
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	3.38 (-4.94 to 12.44)	40.17 (27.8 to 53.73)	2.99 (-6.57 to 13.54)	10.62 (1.4 to 20.69)	-13.62 (-21.36 to -4.32)

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.002 ^[68]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-16.64

Confidence interval

level

95%

sides

2-sided

lower limit

-28.84

upper limit

-4.44

Notes
[68] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.852 ^[69]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

7.24

Confidence interval

level

95%

sides

2-sided

lower limit

-5.73

upper limit

20.21

Notes
[69] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-13.69

upper limit

12.92

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

36.79

Confidence interval

level

95%

sides

2-sided

lower limit

21.19

upper limit

52.38

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months

End point description

Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline, in biochemical marker of bone turnover (s-P1NP) (relative to baseline) at 24 months. Analysis used a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP protocol population did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 24 months

End point values	Placebo-Ext 1	Odanacatib 3 mg-Ext 1	Odanacatib 10 mg-Ext 1	Odanacatib 25 mg-Ext 1	Odanacatib 50 mg-Ext 1
Number of subjects analysed	57	47	42	53	42
Units: Geometric LS Mean percent change
least squares mean (confidence interval 95%)	1.29 (-11.11 to 15.43)	50.52 (30.37 to 73.79)	9.07 (-6.28 to 26.93)	14.6 (0.08 to 31.23)	-20.2 (-31.49 to -7.05)

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 50 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.011 ^[70]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-21.49

Confidence interval

level

95%

sides

2-sided

lower limit

-39.55

upper limit

-3.43

Notes
[70] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 25 mg-Ext 1

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.618 ^[71]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

13.31

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

33.71

Notes
[71] - Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by Hochberg procedure.

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 10 mg-Ext 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

7.77

Confidence interval

level

95%

sides

2-sided

lower limit

-13.46

upper limit

29.01

Difference in Least Squares Means

Statistical analysis description

Comparison groups

Placebo-Ext 1 v Odanacatib 3 mg-Ext 1

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

49.23

Confidence interval

level

95%

sides

2-sided

lower limit

23.86

upper limit

74.59

Secondary: Percentage Change From Baseline in Total Hip BMD at 36 Months

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End point title

Percentage Change From Baseline in Total Hip BMD at 36 Months

End point description

Percentage change in Total Hip BMD (relative to baseline) at 36 Months. This analysis was performed at Month 36 using the PP population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	17	12	11	9	12	19	15	17
Units: Percent Change
least squares mean (confidence interval 95%)	-0.77 (-2.92 to 1.38)	1.16 (-0.86 to 3.17)	-0.63 (-2.59 to 1.33)	2.75 (0.42 to 5.07)	0.96 (-1.48 to 3.39)	4.61 (1.93 to 7.3)	1.64 (-0.69 to 3.97)	5.7 (3.85 to 7.54)	-0.48 (-2.56 to 1.6)	5.83 (3.87 to 7.79)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

6.31

Confidence interval

level

95%

sides

2-sided

lower limit

3.44

upper limit

9.17

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 36 Months

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End point title

Percentage Change From Baseline in Femoral Neck BMD at 36 Months

End point description

Percentage change in femoral neck BMD (relative to baseline) at 36 months. This analysis was performed at Month 36 using the PP population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	17	12	11	9	12	19	15	17
Units: Percent Change
least squares mean (confidence interval 95%)	-0.52 (-2.67 to 1.63)	1.03 (-0.98 to 3.04)	-1.04 (-2.99 to 0.92)	2.26 (-0.06 to 4.59)	-0.14 (-2.57 to 2.3)	5.06 (2.38 to 7.74)	0.8 (-1.52 to 3.13)	7.23 (5.38 to 9.07)	2.26 (0.19 to 4.34)	4.97 (3.01 to 6.93)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

2.71

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

5.57

Secondary: Percentage Change From Baseline in Trochanter BMD at 36 Months

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End point title

Percentage Change From Baseline in Trochanter BMD at 36 Months

End point description

Percentage change in trochanter BMD (relative to baseline) at 36 months. This analysis was performed at Month 36 using the PP population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	17	12	11	9	12	19	15	17
Units: Percent Change
least squares mean (confidence interval 95%)	-0.46 (-3.71 to 2.79)	2.32 (-0.72 to 5.36)	-1.04 (-4 to 1.92)	4.53 (1.01 to 8.04)	0.66 (-3.02 to 4.34)	8.21 (4.16 to 12.27)	1.14 (-2.38 to 4.65)	7.97 (5.18 to 10.76)	-0.69 (-3.83 to 2.46)	7.44 (4.48 to 10.41)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

8.13

Confidence interval

level

95%

sides

2-sided

lower limit

3.8

upper limit

12.46

Secondary: Percentage Change From Baseline in Total Body BMD at 36 Months

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End point title

Percentage Change From Baseline in Total Body BMD at 36 Months

End point description

Percentage change in total body BMD (relative to baseline) at 36 months. This analysis was performed at Month 36 using the PP population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	14	16	13	12	9	12	18	15	17
Units: Percent Change
least squares mean (confidence interval 95%)	0.13 (-2.12 to 2.38)	-2.2 (-4.45 to 0.05)	-3.63 (-5.74 to -1.52)	0.28 (-2.07 to 2.62)	-2.28 (-4.71 to 0.15)	-1.22 (-4.03 to 1.58)	-0.85 (-3.29 to 1.58)	0.56 (-1.43 to 2.54)	-1.84 (-4.02 to 0.34)	-0.38 (-2.43 to 1.67)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

-1.54

upper limit

4.46

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 36 Months

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End point title

Percentage Change From Baseline in Distal Forearm BMD at 36 Months

End point description

Percentage change in distal forearm BMD (relative to baseline) at 36 months. This analysis was performed at Month 36 using the PP population, which included participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from Month 30 to 36.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	15	16	13	12	10	12	18	14	17
Units: Percent Change
least squares mean (confidence interval 95%)	-2.08 (-4.6 to 0.43)	-4.04 (-6.47 to -1.61)	-6.59 (-8.95 to -4.23)	-6.34 (-8.96 to -3.73)	-1.74 (-4.46 to 0.97)	-3.74 (-6.71 to -0.76)	-2.39 (-5.11 to 0.32)	0.53 (-1.69 to 2.74)	-2.73 (-5.25 to -0.22)	-0.26 (-2.55 to 2.03)

Difference in Least Squares Means

Statistical analysis description

test

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

2.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

5.88

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 36 Months

End point description

Geometric mean percentage change from baseline in biochemical marker of bone turnover (urinary N-telopeptides of Type I collagen [u-NTx]) at 36 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36, using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	15	13	16	13	11	10	18	14	17
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	-17.43 (-39.06 to 11.86)	-55.12 (-66.51 to 39.85)	-11.9 (-35.76 to 20.83)	-57.17 (-67.75 to -43.12)	-12.15 (-35.91 to 20.43)	-49.1 (-63.88 to -28.27)	14.26 (-20.17 to 63.53)	-52.11 (-63.33 to -37.45)	27.55 (-5.86 to 72.8)	-50.51 (-62.44 to -34.81)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

-78.06

Confidence interval

level

95%

sides

2-sided

lower limit

-119.2

upper limit

-36.92

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 36 Months

Top of page

End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 36 Months

End point description

Geometric mean percentage change from baseline in biochemical marker of bone turnover (serum C-telopeptides of Type 1 collagen [s-CTx]) at 36 Months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	15	13	16	13	11	9	18	14	17
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	-0.09 (-28.93 to 40.46)	-41.3 (-57.74 to -18.47)	-4.69 (-33.13 to 35.85)	-44.62 (-59.72 to -23.88)	18.24 (-16.98 to 68.41)	-26.26 (-49.81 to 8.33)	61.14 (5.5 to 146.12)	-36.71 (-53.09 to -14.6)	10.32 (-21.52 to 55.1)	-23.93 (-44.15 to 3.63)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

-34.25

Confidence interval

level

95%

sides

2-sided

lower limit

-78.7

upper limit

10.2

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months

End point description

Geometric mean percentage change from baseline in Biochemical marker of bone turnover (urinary total deoxypyridinolines [u-DPyr]) at 36 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	15	13	14	13	11	10	18	14	17
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	-18.69 (-41.68 to 13.36)	-14.95 (-38.27 to 17.18)	-7.82 (-34.76 to 30.26)	-26.27 (-47.1 to 2.76)	-4.69 (-32.51 to 34.6)	0.43 (-31 to 46.19)	-9.16 (-38.64 to 34.48)	-16.41 (-37.59 to 11.97)	22.41 (-12.2 to 70.66)	-16.84 (-38.49 to 12.45)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Least Squares Means

Point estimate

-39.25

Confidence interval

level

95%

sides

2-sided

lower limit

-87.17

upper limit

8.68

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months

End point description

Geometric mean percentage change from baseline, in biochemical marker of bone turnover (serum bone-specific alkaline phosphatase [s-BSAP]) at 36 months. This analysis was geometric mean percentage change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	14	16	13	11	12	18	14	17
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	7.73 (-7.32 to 25.24)	10.86 (-3.69 to 27.62)	14.26 (-1.77 to 32.91)	9.13 (-5.2 to 25.62)	12.95 (-3.41 to 32.08)	8.49 (-8.48 to 28.62)	33.74 (13.71 to 57.31)	11.12 (-2.67 to 26.86)	1.3 (-12.85 to 17.76)	17.9 (2.83 to 35.17)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

16.59

Confidence interval

level

95%

sides

2-sided

lower limit

-5.67

upper limit

38.85

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months

End point description

Geometric mean percentage change from baseline in biochemical marker of bone turnover (serum N-terminal propeptide of Type 1 collagen [s-P1NP]) at 36 months. This analysis was geometric mean percentage change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	16	14	15	13	11	12	18	14	17
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	-20.79 (-40.08 to 4.72)	-18.79 (-37.44 to 5.42)	-13.11 (-34.35 to 15)	-21.08 (-39.75 to 3.37)	8.58 (-18.75 to 45.11)	12.44 (-17.98 to 54.13)	22.57 (-9.27 to 65.59)	-8.14 (-28.14 to 17.42)	-0.77 (-24.94 to 31.18)	-6.2 (-27.2 to 20.86)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

-5.43

Confidence interval

level

95%

sides

2-sided

lower limit

-42.04

upper limit

31.18

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5b]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5b]) at 36 Months

End point description

Geometric mean percentage change from baseline in biochemical marker of bone turnover (serum bone tartrate-resistant acid phosphatase isoform 5b [TRAP 5b]) at 36 months. This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using the PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	10	11	10	12	10	9	10	15	10	15
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	52.98 (29.87 to 80.21)	52.37 (30.34 to 78.12)	33.25 (13.12 to 56.97)	59.37 (37.24 to 85.08)	56.71 (33.04 to 84.6)	82.94 (53.93 to 117.42)	56.42 (32.79 to 84.26)	77.9 (55.63 to 103.36)	47.61 (25.3 to 73.88)	96.7 (72.08 to 124.85)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

49.1

Confidence interval

level

95%

sides

2-sided

lower limit

13.37

upper limit

84.83

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months

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End point title

Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months

End point description

Geometric mean percentage change from baseline in biochemical marker of bone turnover (serum cross-linked carboxyterminal telopeptides of Type I collagen [1-CTP]) at 36 Months. This analysis was geometric mean percentage change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a PP population, from which participants with important protocol deviations and major protocol violators were excluded. The PP approach did not estimate missing data.

End point type

Secondary

End point timeframe

Baseline and 36 months

End point values	Placebo/Placebo-Ext 2	Placebo/Odanacatib 50 mg-Ext 2	Odanacatib 3 mg/Placebo-Ext 2	Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Odanacatib 10 mg/Placebo-Ext 2	Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Odanacatib 25 mg/Placebo-Ext 2	Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Odanacatib 50 mg/Placebo-Ext 2	Odanacatib 50 mg/Odanacatib 50 mg-Ext 2
Number of subjects analysed	14	13	14	16	12	11	11	19	15	18
Units: Geometric Mean Percent Change
least squares mean (confidence interval 95%)	7.4 (-16.78 to 38.6)	193.91 (125.61 to 282.89)	1.67 (-21.41 to 31.53)	187.37 (126.25 to 264.99)	58.76 (20.27 to 109.56)	188.5 (116.34 to 284.74)	77.94 (33.46 to 137.24)	231.93 (166.74 to 313.05)	27.2 (-0.61 to 62.79)	236.64 (168.69 to 321.76)

Difference in Least Squares Means

Comparison groups

Odanacatib 50 mg/Placebo-Ext 2 v Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Least Squares Means

Point estimate

209.44

Confidence interval

level

95%

sides

2-sided

lower limit

127.14

upper limit

291.73

Adverse events

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Timeframe for reporting adverse events

Adverse Events data were collected up to 120 months (from start of study medication, up to 14 days after the last dose).

Adverse event reporting additional description

The Safety Analysis was based on the All Participants as Treated (APaT) population, which included all participants who took at least one dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

10.1

Reporting group title

Years 1-2 Placebo/Placebo-Ext 1

Reporting group description

One placebo tablet once a week

Reporting group title

Years 1-2 Odanacatib 3 mg/Odanacatib 3 mg-Ext 1

Reporting group description

One odanacatib 3 mg tablet once a week

Reporting group title

Years 1-2 Odanacatib 10 mg/Odanacatib 10 mg-Ext 1

Reporting group description

One odanacatib 10 mg tablet once a week

Reporting group title

Years 1-2 Odanacatib 25 mg/Odanacatib 25 mg-Ext 1

Reporting group description

One odanacatib 25 mg tablet once a week

Reporting group title

Years 1-2 Odanacatib 50 mg/Odanacatib 50 mg-Ext 1

Reporting group description

One odanacatib 50 mg tablet once a week

Reporting group title

Year 3 Placebo/Placebo-Ext 2

Reporting group description

Reporting group title

Year 3 Placebo/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 3 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 3 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 10 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 10 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 25 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 25 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 50 mg/Placebo-Ext 2

Reporting group description

Reporting group title

Year 3 Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Reporting group description

Reporting group title

Years 4-5 Combined Group A.1: Odanacatib 50 mg

Reporting group description

Combined Group A.1 consists of participants who received odanacatib 50 mg once a week during Year 3. During this 24-month extension (Years 4-5), these participants continued to receive odanacatib 50 mg once a week.

Reporting group title

Years 4-5 Combined Group A.2: Odanacatib 50 mg

Reporting group description

Combined Group A.2 consists of participants who received placebo or odanacatib 3 mg in Years 1, 2 and 3. During this 24-month extension (Years 4-5), these participants received odanacatib 50 mg once a week.

Reporting group title

Years 4-5 Combined Group A.3: Placebo

Reporting group description

Combined Group A.3 consists of participants who, during this 24-month extension (Years 4-5), received placebo once a week.

Reporting group title

Years 6-10 Group A: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Years 6-10 Group B: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Years 6-10 Group C: Odanacatib 50 mg once weekly

Reporting group description

Reporting group title

Years 6-10 Group D: Odanacatib 50 mg once weekly

Reporting group description

Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.

Years 1-2 Placebo/Placebo-Ext 1

Years 1-2 Odanacatib 3 mg/Odanacatib 3 mg-Ext 1

Years 1-2 Odanacatib 10 mg/Odanacatib 10 mg-Ext 1

Years 1-2 Odanacatib 25 mg/Odanacatib 25 mg-Ext 1

Years 1-2 Odanacatib 50 mg/Odanacatib 50 mg-Ext 1

Year 3 Placebo/Placebo-Ext 2

Year 3 Placebo/Odanacatib 50 mg-Ext 2

Year 3 Odanacatib 3 mg/Placebo-Ext 2

Year 3 Odanacatib 3 mg/Odanacatib 50 mg-Ext 2

Year 3 Odanacatib 10 mg/Placebo-Ext 2

Year 3 Odanacatib 10 mg/Odanacatib 50 mg-Ext 2

Year 3 Odanacatib 25 mg/Placebo-Ext 2

Year 3 Odanacatib 25 mg/Odanacatib 50 mg-Ext 2

Year 3 Odanacatib 50 mg/Placebo-Ext 2

Year 3 Odanacatib 50 mg/Odanacatib 50 mg-Ext 2

Years 4-5 Combined Group A.1: Odanacatib 50 mg

Years 4-5 Combined Group A.2: Odanacatib 50 mg

Years 4-5 Combined Group A.3: Placebo

Years 6-10 Group A: Odanacatib 50 mg once weekly

Years 6-10 Group B: Odanacatib 50 mg once weekly

Years 6-10 Group C: Odanacatib 50 mg once weekly

Years 6-10 Group D: Odanacatib 50 mg once weekly

Total subjects affected by serious adverse events

subjects affected / exposed

8 / 83 (9.64%)

12 / 82 (14.63%)

10 / 77 (12.99%)

9 / 79 (11.39%)

14 / 78 (17.95%)

2 / 19 (10.53%)

2 / 22 (9.09%)

3 / 18 (16.67%)

2 / 17 (11.76%)

0 / 18 (0.00%)

1 / 17 (5.88%)

1 / 19 (5.26%)

4 / 21 (19.05%)

2 / 18 (11.11%)

1 / 20 (5.00%)

16 / 73 (21.92%)

2 / 27 (7.41%)

8 / 41 (19.51%)

8 / 28 (28.57%)

14 / 34 (41.18%)

6 / 23 (26.09%)

12 / 32 (37.50%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Anal Cancer

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Basal Cell Carcinoma

subjects affected / exposed

1 / 83 (1.20%)

1 / 82 (1.22%)

1 / 77 (1.30%)

1 / 79 (1.27%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 18 (5.56%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

1 / 21 (4.76%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

3 / 41 (7.32%)

2 / 28 (7.14%)

1 / 34 (2.94%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 1

0 / 2

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

1 / 5

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Breast Cancer

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Breast Cancer In Situ

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-Hodgkin's Lymphoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Papillary Thyroid Cancer

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sarcoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Squamous Cell Carcinoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Colon Cancer Metastatic

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

1 / 21 (4.76%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian Neoplasm

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 18 (5.56%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colon Adenoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neurilemmoma Benign

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

1 / 27 (3.70%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bowen's disease

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastric cancer

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Invasive breast carcinoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Invasive ductal breast carcinoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Malignant melanoma

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Malignant melanoma in situ

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ovarian cancer

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatic carcinoma metastatic

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Squamous cell carcinoma of skin

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypertension

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

2 / 77 (2.60%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Orthostatic Hypotension

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Chest Pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Genital Prolapse

subjects affected / exposed

2 / 83 (2.41%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian cyst

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian cyst torsion

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine prolapse

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vaginal prolapse

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Chronic Obstructive Pulmonary Disease

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

1 / 19 (5.26%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Investigations

Electrocardiogram ST-T Change

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Weight Decreased

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Hip Fracture

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

1 / 77 (1.30%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Joint Dislocation

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lumbar Vertebral Fracture

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post Procedural Bile Leak

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Head Injury

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wrist Fracture

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 18 (5.56%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

1 / 21 (4.76%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ankle Fracture

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Fall

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rib Fracture

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Femur fracture

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Incarcerated incisional hernia

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Scar

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary retention postoperative

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Arteriospasm Coronary

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Failure Congestive

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Coronary Artery Occlusion

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocardial Infarction

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial Fibrillation

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

2 / 34 (5.88%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Failure

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Coronary Artery Disease

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Palpitations

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Reversible Ischaemic Neurological Deficit

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Facial Palsy

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sciatica

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral infarction

alternative assessment type: Non-systematic

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dementia Alzheimer's type

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nerve root compression

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraesthesia

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Presyncope

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Immune Thrombocytopenic Purpura

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vertigo Positional

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Cataract

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Macular Hole

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Retinal Detachment

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Anal Fistula

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastritis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hiatus Hernia

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oesophagitis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritonitis

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stomatitis

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal Pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal Pain Lower

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

1 / 20 (5.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Anal Sphincter Atony

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Flatulence

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrooesophageal Reflux Disease

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Inguinal Hernia

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric Ulcer Haemorrhage

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholecystitis

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholelithiasis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

2 / 77 (2.60%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Erythema Nodosum

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 41 (2.44%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Nephrolithiasis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal Failure Chronic

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Hypoparathyroidism

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Foot Deformity

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal Pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Osteoarthritis

subjects affected / exposed

1 / 83 (1.20%)

1 / 82 (1.22%)

1 / 77 (1.30%)

0 / 79 (0.00%)

2 / 78 (2.56%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

1 / 21 (4.76%)

0 / 18 (0.00%)

1 / 20 (5.00%)

4 / 73 (5.48%)

0 / 27 (0.00%)

1 / 41 (2.44%)

1 / 28 (3.57%)

1 / 34 (2.94%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Osteoporotic Fracture

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

1 / 77 (1.30%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intervertebral Disc Degeneration

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal Chest Pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

1 / 19 (5.26%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Trigger Finger

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back Pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lumbar Spinal Stenosis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bursitis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rotator cuff syndrome

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal pain

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bronchitis

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulitis

subjects affected / exposed

1 / 83 (1.20%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ear Infection

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Streptococcal

subjects affected / exposed

0 / 83 (0.00%)

1 / 82 (1.22%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Viral Infection

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

1 / 79 (1.27%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

1 / 83 (1.20%)

1 / 82 (1.22%)

1 / 77 (1.30%)

0 / 79 (0.00%)

1 / 78 (1.28%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

1 / 19 (5.26%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory Tract Infection

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

1 / 17 (5.88%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary Tract Infection

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Wound Infection

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 18 (5.56%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

1 / 23 (4.35%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sialoadenitis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

1 / 27 (3.70%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis bacterial

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

1 / 32 (3.13%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bacterial sepsis

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

1 / 28 (3.57%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulitis intestinal haemorrhagic

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infective exacerbation of chronic obstructive airways disease

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 18 (0.00%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

1 / 34 (2.94%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 83 (0.00%)

0 / 82 (0.00%)

0 / 77 (0.00%)

0 / 79 (0.00%)

0 / 78 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 18 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

1 / 18 (5.56%)

0 / 20 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 41 (0.00%)

0 / 28 (0.00%)

0 / 34 (0.00%)

0 / 23 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Years 1-2 Placebo/Placebo-Ext 1	Years 1-2 Odanacatib 3 mg/Odanacatib 3 mg-Ext 1	Years 1-2 Odanacatib 10 mg/Odanacatib 10 mg-Ext 1	Years 1-2 Odanacatib 25 mg/Odanacatib 25 mg-Ext 1	Years 1-2 Odanacatib 50 mg/Odanacatib 50 mg-Ext 1	Year 3 Placebo/Placebo-Ext 2	Year 3 Placebo/Odanacatib 50 mg-Ext 2	Year 3 Odanacatib 3 mg/Placebo-Ext 2	Year 3 Odanacatib 3 mg/Odanacatib 50 mg-Ext 2	Year 3 Odanacatib 10 mg/Placebo-Ext 2	Year 3 Odanacatib 10 mg/Odanacatib 50 mg-Ext 2	Year 3 Odanacatib 25 mg/Placebo-Ext 2	Year 3 Odanacatib 25 mg/Odanacatib 50 mg-Ext 2	Year 3 Odanacatib 50 mg/Placebo-Ext 2	Year 3 Odanacatib 50 mg/Odanacatib 50 mg-Ext 2	Years 4-5 Combined Group A.1: Odanacatib 50 mg	Years 4-5 Combined Group A.2: Odanacatib 50 mg	Years 4-5 Combined Group A.3: Placebo	Years 6-10 Group A: Odanacatib 50 mg once weekly	Years 6-10 Group B: Odanacatib 50 mg once weekly	Years 6-10 Group C: Odanacatib 50 mg once weekly	Years 6-10 Group D: Odanacatib 50 mg once weekly
Total subjects affected by non serious adverse events
subjects affected / exposed	68 / 83 (81.93%)	66 / 82 (80.49%)	67 / 77 (87.01%)	67 / 79 (84.81%)	66 / 78 (84.62%)	17 / 19 (89.47%)	13 / 22 (59.09%)	16 / 18 (88.89%)	14 / 17 (82.35%)	13 / 18 (72.22%)	15 / 17 (88.24%)	15 / 19 (78.95%)	17 / 21 (80.95%)	14 / 18 (77.78%)	15 / 20 (75.00%)	65 / 73 (89.04%)	23 / 27 (85.19%)	33 / 41 (80.49%)	27 / 28 (96.43%)	34 / 34 (100.00%)	23 / 23 (100.00%)	32 / 32 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Ovarian Neoplasm
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vascular disorders
Flushing
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Haematoma
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	1	0	1	0	1	0	0	2	0	0	0	1	0	0	3	0	0	0	0	1	0
Hypertension
subjects affected / exposed	4 / 83 (4.82%)	7 / 82 (8.54%)	3 / 77 (3.90%)	8 / 79 (10.13%)	4 / 78 (5.13%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	2 / 19 (10.53%)	0 / 21 (0.00%)	2 / 18 (11.11%)	0 / 20 (0.00%)	5 / 73 (6.85%)	2 / 27 (7.41%)	2 / 41 (4.88%)	3 / 28 (10.71%)	6 / 34 (17.65%)	5 / 23 (21.74%)	3 / 32 (9.38%)
occurrences all number	4	7	3	8	4	0	1	0	0	0	0	0	0	2	0	6	2	2	3	7	5	3
Phlebitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Varicose Vein
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	2 / 41 (4.88%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0	1	0	2	0	0	1	1
General disorders and administration site conditions
Calcinosis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Chest Discomfort
subjects affected / exposed	1 / 83 (1.20%)	2 / 82 (2.44%)	0 / 77 (0.00%)	2 / 79 (2.53%)	2 / 78 (2.56%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	1	3	0	2	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Chest Pain
subjects affected / exposed	4 / 83 (4.82%)	1 / 82 (1.22%)	1 / 77 (1.30%)	2 / 79 (2.53%)	3 / 78 (3.85%)	2 / 19 (10.53%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	1 / 20 (5.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	1 / 41 (2.44%)	2 / 28 (7.14%)	1 / 34 (2.94%)	1 / 23 (4.35%)	2 / 32 (6.25%)
occurrences all number	8	1	1	2	3	2	0	0	0	0	0	0	1	0	1	1	1	1	3	1	2	2
Fatigue
subjects affected / exposed	6 / 83 (7.23%)	2 / 82 (2.44%)	2 / 77 (2.60%)	1 / 79 (1.27%)	3 / 78 (3.85%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	6	2	2	1	3	1	2	0	1	0	1	0	0	1	0	3	0	0	0	0	0	1
Influenza Like Illness
subjects affected / exposed	3 / 83 (3.61%)	1 / 82 (1.22%)	3 / 77 (3.90%)	2 / 79 (2.53%)	6 / 78 (7.69%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	3	1	5	2	7	0	0	1	0	0	1	0	0	1	0	2	1	0	1	1	1	0
Oedema Peripheral
subjects affected / exposed	3 / 83 (3.61%)	1 / 82 (1.22%)	1 / 77 (1.30%)	2 / 79 (2.53%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	3 / 20 (15.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	3	1	1	2	2	0	0	0	0	1	1	1	0	0	3	2	0	0	2	2	3	0
Immune system disorders
Allergy To Arthropod Sting
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	0	0	0
Reproductive system and breast disorders
Breast Mass
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	1	1
Fibrocystic Breast Disease
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pelvic Pain
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Vulvovaginal Discomfort
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
subjects affected / exposed	2 / 83 (2.41%)	3 / 82 (3.66%)	3 / 77 (3.90%)	5 / 79 (6.33%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	3	3	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asthma
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	3 / 41 (7.32%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	4	0	3	0	1	0	1
Dyspnoea
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	3 / 41 (7.32%)	3 / 28 (10.71%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	4	0	3	3	0	1	0
Dyspnoea Exertional
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	1	1	0
Emphysema
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemoptysis
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	2 / 83 (2.41%)	2 / 82 (2.44%)	2 / 77 (2.60%)	3 / 79 (3.80%)	3 / 78 (3.85%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 18 (5.56%)	1 / 20 (5.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	3 / 41 (7.32%)	0 / 28 (0.00%)	2 / 34 (5.88%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	4	2	5	4	3	0	0	0	0	0	2	0	1	1	1	4	0	3	0	2	0	1
Psychiatric disorders
Insomnia
subjects affected / exposed	7 / 83 (8.43%)	3 / 82 (3.66%)	4 / 77 (5.19%)	3 / 79 (3.80%)	6 / 78 (7.69%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	2 / 41 (4.88%)	2 / 28 (7.14%)	1 / 34 (2.94%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	7	4	4	3	6	0	0	0	0	0	0	0	0	0	0	2	0	2	2	1	1	1
Alcoholism
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	3 / 77 (3.90%)	1 / 79 (1.27%)	0 / 78 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	0	0	3	1	0	2	1	0	0	0	0	0	0	1	0	0	0	0	1	1	1	1
Depression
subjects affected / exposed	5 / 83 (6.02%)	4 / 82 (4.88%)	5 / 77 (6.49%)	3 / 79 (3.80%)	3 / 78 (3.85%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	3 / 27 (11.11%)	1 / 41 (2.44%)	4 / 28 (14.29%)	3 / 34 (8.82%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	5	4	5	3	3	0	2	0	0	0	0	0	0	0	0	1	3	1	5	3	4	2
Dysthymic Disorder
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Stress
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0
Investigations
Weight Increased
subjects affected / exposed	4 / 83 (4.82%)	2 / 82 (2.44%)	3 / 77 (3.90%)	5 / 79 (6.33%)	3 / 78 (3.85%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	4	2	3	6	3	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	0 / 77 (0.00%)	5 / 79 (6.33%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	4 / 23 (17.39%)	3 / 32 (9.38%)
occurrences all number	1	4	0	7	3	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	4	3
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	2 / 77 (2.60%)	4 / 79 (5.06%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	4 / 23 (17.39%)	2 / 32 (6.25%)
occurrences all number	1	5	2	6	1	0	0	1	0	0	0	0	0	0	0	1	1	0	0	0	4	2
Blood 1,25-Dihydroxycholecalciferol Increased
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	1	2	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood Cholesterol Increased
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	0	0	2	0	0	0	0	2	0	1	0	0	0	0
Blood Glucose Increased
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	2 / 79 (2.53%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	3	2	0	0	0	0	1	0	0	0	1	0	0	0	1	0	0	0	1
Blood Parathyroid Hormone Increased
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	1 / 77 (1.30%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	5 / 73 (6.85%)	3 / 27 (11.11%)	2 / 41 (4.88%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	1	0	0	2	1	1	1	0	5	0	0	0	1	13	5	3	0	0	0	0
Blood Pressure Increased
subjects affected / exposed	0 / 83 (0.00%)	2 / 82 (2.44%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 21 (9.52%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	0	0	0	0	2	1	0	0	0	0	0	0	0	0
Blood Triglycerides Increased
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	2 / 41 (4.88%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	1	0	2	0	0	0	0
Carotid Bruit
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0
Glucose Urine Present
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
High Density Lipoprotein Decreased
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lymphocyte Count Decreased
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	2 / 77 (2.60%)	1 / 79 (1.27%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	3 / 18 (16.67%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	2	1	3	0	0	0	0	0	0	0	0	3	0	1	0	0	0	0	0	0
Weight Decreased
subjects affected / exposed	2 / 83 (2.41%)	1 / 82 (1.22%)	2 / 77 (2.60%)	1 / 79 (1.27%)	4 / 78 (5.13%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	2 / 34 (5.88%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	2	1	2	1	4	0	1	0	1	0	1	0	0	1	0	1	1	1	0	3	2	2
White Blood Cells Urine Positive
subjects affected / exposed	0 / 83 (0.00%)	2 / 82 (2.44%)	2 / 77 (2.60%)	0 / 79 (0.00%)	2 / 78 (2.56%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	3	2	0	2	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Arthropod Bite
subjects affected / exposed	0 / 83 (0.00%)	3 / 82 (3.66%)	2 / 77 (2.60%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	3	2	2	0	0	0	0	1	0	0	0	0	0	0	2	0	0	1	1	0	0
Arthropod Sting
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0	0	1	2	0	0	0	0
Contusion
subjects affected / exposed	5 / 83 (6.02%)	2 / 82 (2.44%)	5 / 77 (6.49%)	2 / 79 (2.53%)	3 / 78 (3.85%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	2 / 41 (4.88%)	3 / 28 (10.71%)	0 / 34 (0.00%)	1 / 23 (4.35%)	3 / 32 (9.38%)
occurrences all number	5	4	8	3	3	1	0	0	2	0	0	0	0	0	0	6	0	2	3	0	2	7
Epicondylitis
subjects affected / exposed	1 / 83 (1.20%)	2 / 82 (2.44%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	2 / 28 (7.14%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	2	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0	0	2	0	0	0
Fall
subjects affected / exposed	2 / 83 (2.41%)	2 / 82 (2.44%)	1 / 77 (1.30%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	2 / 18 (11.11%)	0 / 20 (0.00%)	3 / 73 (4.11%)	0 / 27 (0.00%)	2 / 41 (4.88%)	3 / 28 (10.71%)	4 / 34 (11.76%)	5 / 23 (21.74%)	4 / 32 (12.50%)
occurrences all number	3	2	1	0	1	0	1	0	1	0	0	0	1	2	0	4	0	2	12	8	6	9
Humerus Fracture
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	2	1	0	0	0	0	0	0	0	0	0	0	0
Limb Injury
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	2	0	0	0	0	0	1	0	0	0	1	1	0
Muscle Strain
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	2 / 41 (4.88%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	0	0	0	0	0	0	0	0	2	1	0	0	0
Wound
subjects affected / exposed	0 / 83 (0.00%)	2 / 82 (2.44%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Procedural Pain
subjects affected / exposed	1 / 83 (1.20%)	2 / 82 (2.44%)	0 / 77 (0.00%)	0 / 79 (0.00%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	2	0	0	3	0	0	1	0	0	2	0	2	1	0	0	1	0	1	0	0	0
Radius Fracture
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	2 / 27 (7.41%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	2	0	0	0	0	0
Skull Fractured Base
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Spinal Compression Fracture
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Spinal Fracture
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Subdural Haematoma
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Thoracic Vertebral Fracture
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tooth Fracture
subjects affected / exposed	1 / 83 (1.20%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	1	1	0	1	0	1	0	0	0	0	0	0	0	0	0	2	0	0	1	2	4	0
Wrist Fracture
subjects affected / exposed	2 / 83 (2.41%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	1	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0	0	1	1	0	0
Laceration
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	2 / 77 (2.60%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	3 / 41 (7.32%)	1 / 28 (3.57%)	2 / 34 (5.88%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	0	0	2	0	1	0	2	0	0	0	0	0	0	1	0	1	1	3	1	3	1	3
Ligament sprain
subjects affected / exposed	4 / 83 (4.82%)	1 / 82 (1.22%)	2 / 77 (2.60%)	3 / 79 (3.80%)	3 / 78 (3.85%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	1 / 41 (2.44%)	1 / 28 (3.57%)	2 / 34 (5.88%)	0 / 23 (0.00%)	4 / 32 (12.50%)
occurrences all number	4	1	2	3	5	0	2	0	0	1	0	1	0	0	0	1	0	1	1	2	0	4
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Atrial Flutter
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mitral Valve Prolapse
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	5 / 78 (6.41%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	2	5	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1	0	0
Tachycardia
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	11 / 83 (13.25%)	9 / 82 (10.98%)	10 / 77 (12.99%)	9 / 79 (11.39%)	9 / 78 (11.54%)	0 / 19 (0.00%)	2 / 22 (9.09%)	1 / 18 (5.56%)	3 / 17 (17.65%)	1 / 18 (5.56%)	1 / 17 (5.88%)	1 / 19 (5.26%)	1 / 21 (4.76%)	1 / 18 (5.56%)	1 / 20 (5.00%)	2 / 73 (2.74%)	2 / 27 (7.41%)	1 / 41 (2.44%)	2 / 28 (7.14%)	1 / 34 (2.94%)	3 / 23 (13.04%)	3 / 32 (9.38%)
occurrences all number	13	9	10	10	12	0	2	1	3	1	1	1	1	1	1	2	2	2	3	1	4	4
Memory Impairment
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	0	1	0	0	0	2	0	0	0	0	1	1
Paraesthesia
subjects affected / exposed	2 / 83 (2.41%)	0 / 82 (0.00%)	2 / 77 (2.60%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	1 / 20 (5.00%)	3 / 73 (4.11%)	1 / 27 (3.70%)	2 / 41 (4.88%)	2 / 28 (7.14%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	2	0	2	1	0	0	0	1	0	0	1	0	1	0	1	3	1	3	2	1	1	0
Sciatica
subjects affected / exposed	2 / 83 (2.41%)	2 / 82 (2.44%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	1 / 41 (2.44%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	2	4	0	1	1	0	1	0	2	0	0	0	0	1	0	3	0	1	1	0	0	3
Somnolence
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tension Headache
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	1	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tremor
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	1 / 77 (1.30%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	2	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	1	0	0	0
Trigeminal Neuralgia
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	4 / 83 (4.82%)	7 / 82 (8.54%)	8 / 77 (10.39%)	3 / 79 (3.80%)	4 / 78 (5.13%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	2 / 18 (11.11%)	1 / 20 (5.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	2 / 28 (7.14%)	3 / 34 (8.82%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	5	9	10	3	4	0	0	1	1	0	1	0	0	3	1	3	0	0	2	3	2	2
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Tinnitus
subjects affected / exposed	2 / 83 (2.41%)	1 / 82 (1.22%)	2 / 77 (2.60%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	2 / 34 (5.88%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	2	1	2	1	1	0	0	0	0	0	0	0	0	1	0	0	1	0	0	3	2	0
Tympanosclerosis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	4 / 83 (4.82%)	0 / 82 (0.00%)	3 / 77 (3.90%)	1 / 79 (1.27%)	3 / 78 (3.85%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	2 / 18 (11.11%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	5 / 34 (14.71%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	5	0	3	1	3	1	0	1	0	2	0	0	0	0	0	0	0	0	0	7	1	1
Vertigo Positional
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Cataract
subjects affected / exposed	2 / 83 (2.41%)	2 / 82 (2.44%)	4 / 77 (5.19%)	0 / 79 (0.00%)	2 / 78 (2.56%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	2 / 19 (10.53%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	2 / 73 (2.74%)	2 / 27 (7.41%)	3 / 41 (7.32%)	0 / 28 (0.00%)	6 / 34 (17.65%)	6 / 23 (26.09%)	1 / 32 (3.13%)
occurrences all number	2	2	4	0	3	0	1	1	0	0	0	3	0	1	0	2	4	3	0	9	10	1
Conjunctivitis Allergic
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0
Eye Pruritus
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Macular Degeneration
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	0
Gastrointestinal disorders
Abdominal Pain Upper
subjects affected / exposed	2 / 83 (2.41%)	5 / 82 (6.10%)	5 / 77 (6.49%)	0 / 79 (0.00%)	5 / 78 (6.41%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	2 / 27 (7.41%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	1 / 23 (4.35%)	3 / 32 (9.38%)
occurrences all number	2	5	5	0	5	0	0	0	0	0	0	0	0	0	0	1	2	0	1	1	1	4
Abdominal Pain
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	2 / 77 (2.60%)	2 / 79 (2.53%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	2 / 17 (11.76%)	0 / 19 (0.00%)	2 / 21 (9.52%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	2 / 41 (4.88%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	2 / 32 (6.25%)
occurrences all number	1	0	2	4	2	0	0	0	0	1	2	0	2	0	0	1	0	3	0	0	0	3
Anal Fissure
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	1 / 77 (1.30%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	3 / 83 (3.61%)	8 / 82 (9.76%)	6 / 77 (7.79%)	3 / 79 (3.80%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	3 / 73 (4.11%)	1 / 27 (3.70%)	0 / 41 (0.00%)	2 / 28 (7.14%)	2 / 34 (5.88%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	3	8	7	3	1	1	0	0	0	0	0	0	0	0	0	4	1	0	3	2	2	1
Diarrhoea
subjects affected / exposed	7 / 83 (8.43%)	4 / 82 (4.88%)	8 / 77 (10.39%)	3 / 79 (3.80%)	7 / 78 (8.97%)	1 / 19 (5.26%)	2 / 22 (9.09%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	3 / 20 (15.00%)	2 / 73 (2.74%)	3 / 27 (11.11%)	0 / 41 (0.00%)	2 / 28 (7.14%)	2 / 34 (5.88%)	4 / 23 (17.39%)	2 / 32 (6.25%)
occurrences all number	7	5	8	3	10	1	2	0	0	0	0	0	0	1	0	3	3	0	2	3	5	2
Dry Mouth
subjects affected / exposed	0 / 83 (0.00%)	2 / 82 (2.44%)	2 / 77 (2.60%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	2	2	1	1	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0	1
Duodenal Ulcer
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	4 / 83 (4.82%)	2 / 82 (2.44%)	3 / 77 (3.90%)	3 / 79 (3.80%)	5 / 78 (6.41%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	3 / 73 (4.11%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	4 / 23 (17.39%)	3 / 32 (9.38%)
occurrences all number	6	3	4	3	5	0	0	0	0	0	0	1	0	0	0	4	0	0	0	1	4	3
Faecal Incontinence
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Flatulence
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	1 / 77 (1.30%)	2 / 79 (2.53%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	1	2	1	0	0	0	1	0	0	0	0	0	1	0	0	1	1	0	0	0
Gastric Disorder
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Gastric Polyps
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Gastric Ulcer
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0	0
Gastritis
subjects affected / exposed	0 / 83 (0.00%)	3 / 82 (3.66%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	2 / 20 (10.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	3	0	1	1	0	0	0	0	0	1	1	0	0	2	0	1	0	1	2	1	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	4 / 77 (5.19%)	5 / 79 (6.33%)	3 / 78 (3.85%)	2 / 19 (10.53%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 21 (9.52%)	0 / 18 (0.00%)	1 / 20 (5.00%)	3 / 73 (4.11%)	2 / 27 (7.41%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	1	3	4	7	3	2	1	0	0	0	0	0	2	0	1	3	2	0	1	0	2	2
Gingival Swelling
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Inguinal Hernia
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Irritable Bowel Syndrome
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	3 / 77 (3.90%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	1	0	3	0	0	1	0	1	3	0	1	0	0	0	0	1	0	0	1	0	0	1
Mouth Ulceration
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Nausea
subjects affected / exposed	8 / 83 (9.64%)	4 / 82 (4.88%)	6 / 77 (7.79%)	6 / 79 (7.59%)	5 / 78 (6.41%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	2 / 27 (7.41%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	8	6	7	7	7	1	0	0	1	0	1	0	0	0	0	1	2	1	0	0	0	0
Oesophagitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	3 / 34 (8.82%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	2	1	0	0	0	2	0	0	0	3	0	0
Rectal Haemorrhage
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	2 / 79 (2.53%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	4	1	0	0	0	0	0	0	0	0	1	0	2	0	0	1	1	0	0
Toothache
subjects affected / exposed	4 / 83 (4.82%)	3 / 82 (3.66%)	4 / 77 (5.19%)	2 / 79 (2.53%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	7	4	6	2	2	0	0	1	0	0	0	0	0	1	0	4	0	0	1	1	0	0
Upper Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 83 (1.20%)	1 / 82 (1.22%)	3 / 77 (3.90%)	4 / 79 (5.06%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	1	3	4	1	1	0	1	0	0	0	0	0	0	0	2	1	1	0	1	1	0
Skin and subcutaneous tissue disorders
Actinic Keratosis
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	2 / 77 (2.60%)	2 / 79 (2.53%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	2 / 28 (7.14%)	1 / 34 (2.94%)	0 / 23 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	1	2	2	0	0	0	0	0	0	0	0	0	1	0	0	0	1	2	1	0	4
Dermatitis Atopic
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	2 / 23 (8.70%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	3	1
Ecchymosis
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Granuloma Annulare
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hyperkeratosis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	1	0	0	1	0	1
Hypertrichosis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lichen Planus
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Neurodermatitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	2 / 77 (2.60%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	1 / 41 (2.44%)	2 / 28 (7.14%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	2	0	0	0	0	1	0	0	0	0	0	1	0	2	1	1	2	0	0	0
Psoriasis
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	7 / 83 (8.43%)	4 / 82 (4.88%)	5 / 77 (6.49%)	2 / 79 (2.53%)	3 / 78 (3.85%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	2 / 18 (11.11%)	1 / 20 (5.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	2 / 34 (5.88%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	10	4	6	2	3	1	0	2	0	0	0	0	0	2	3	2	1	1	0	2	2	0
Rash Erythematous
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Rash Papular
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Sebaceous Hyperplasia
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin Irritation
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin Lesion
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	3 / 77 (3.90%)	2 / 79 (2.53%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	1	0	3	3	0	0	0	1	0	0	0	0	0	0	0	0	1	2	0	1	0	1
Urticaria
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	2 / 79 (2.53%)	0 / 78 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	1	0	2	0	3	1	0	0	0	0	0	0	0	0	0	0	2	0	1	2	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Thyroiditis Chronic
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	3 / 83 (3.61%)	2 / 82 (2.44%)	4 / 77 (5.19%)	3 / 79 (3.80%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	3	2	4	3	2	0	0	0	0	0	0	0	0	0	0	2	1	0	1	2	2	0
Arthralgia
subjects affected / exposed	13 / 83 (15.66%)	12 / 82 (14.63%)	12 / 77 (15.58%)	14 / 79 (17.72%)	12 / 78 (15.38%)	3 / 19 (15.79%)	1 / 22 (4.55%)	1 / 18 (5.56%)	1 / 17 (5.88%)	1 / 18 (5.56%)	1 / 17 (5.88%)	2 / 19 (10.53%)	3 / 21 (14.29%)	0 / 18 (0.00%)	3 / 20 (15.00%)	9 / 73 (12.33%)	4 / 27 (14.81%)	6 / 41 (14.63%)	5 / 28 (17.86%)	4 / 34 (11.76%)	8 / 23 (34.78%)	3 / 32 (9.38%)
occurrences all number	24	16	13	17	14	4	1	1	1	1	1	2	4	0	4	13	4	8	10	4	8	3
Back Pain
subjects affected / exposed	10 / 83 (12.05%)	17 / 82 (20.73%)	9 / 77 (11.69%)	14 / 79 (17.72%)	11 / 78 (14.10%)	2 / 19 (10.53%)	5 / 22 (22.73%)	1 / 18 (5.56%)	2 / 17 (11.76%)	1 / 18 (5.56%)	1 / 17 (5.88%)	4 / 19 (21.05%)	2 / 21 (9.52%)	1 / 18 (5.56%)	0 / 20 (0.00%)	8 / 73 (10.96%)	5 / 27 (18.52%)	1 / 41 (2.44%)	6 / 28 (21.43%)	7 / 34 (20.59%)	5 / 23 (21.74%)	2 / 32 (6.25%)
occurrences all number	12	19	11	19	13	2	5	1	2	1	1	5	2	1	0	11	7	1	6	9	7	2
Bone Pain
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0
Bursitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	1 / 20 (5.00%)	2 / 73 (2.74%)	2 / 27 (7.41%)	1 / 41 (2.44%)	1 / 28 (3.57%)	1 / 34 (2.94%)	1 / 23 (4.35%)	2 / 32 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	1	0	1	2	2	1	1	1	1	2
Costochondritis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dupuytren's Contracture
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	0	0
Foot Deformity
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 18 (11.11%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Joint Stiffness
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
Monarthritis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1	0	0
Muscle Contracture
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Muscle Spasms
subjects affected / exposed	4 / 83 (4.82%)	7 / 82 (8.54%)	7 / 77 (9.09%)	3 / 79 (3.80%)	12 / 78 (15.38%)	1 / 19 (5.26%)	2 / 22 (9.09%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 18 (5.56%)	2 / 20 (10.00%)	3 / 73 (4.11%)	1 / 27 (3.70%)	1 / 41 (2.44%)	1 / 28 (3.57%)	1 / 34 (2.94%)	2 / 23 (8.70%)	1 / 32 (3.13%)
occurrences all number	4	7	7	3	12	1	3	1	0	0	0	0	1	1	2	3	1	1	1	1	2	1
Muscular Weakness
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	2 / 34 (5.88%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	1	2	0	0	0	0	0	0	0	0	1	0	0	0	2	1	0
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	2 / 77 (2.60%)	3 / 79 (3.80%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	0	2	3	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	3
Musculoskeletal Discomfort
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal Pain
subjects affected / exposed	5 / 83 (6.02%)	3 / 82 (3.66%)	5 / 77 (6.49%)	10 / 79 (12.66%)	4 / 78 (5.13%)	2 / 19 (10.53%)	1 / 22 (4.55%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	3 / 21 (14.29%)	2 / 18 (11.11%)	0 / 20 (0.00%)	4 / 73 (5.48%)	1 / 27 (3.70%)	6 / 41 (14.63%)	3 / 28 (10.71%)	4 / 34 (11.76%)	5 / 23 (21.74%)	4 / 32 (12.50%)
occurrences all number	5	3	5	11	4	2	1	1	1	0	0	0	3	2	0	5	1	6	6	4	6	4
Musculoskeletal Stiffness
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	1 / 78 (1.28%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	0	1	1	1	0	0	0	0	0	2	0	0	1	0	0	0	1	0	0
Neck Pain
subjects affected / exposed	3 / 83 (3.61%)	0 / 82 (0.00%)	2 / 77 (2.60%)	5 / 79 (6.33%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	2 / 21 (9.52%)	0 / 18 (0.00%)	4 / 20 (20.00%)	3 / 73 (4.11%)	2 / 27 (7.41%)	1 / 41 (2.44%)	0 / 28 (0.00%)	3 / 34 (8.82%)	3 / 23 (13.04%)	1 / 32 (3.13%)
occurrences all number	3	0	2	5	0	0	0	1	0	0	0	2	2	0	4	3	2	1	0	4	4	1
Osteoarthritis
subjects affected / exposed	2 / 83 (2.41%)	5 / 82 (6.10%)	4 / 77 (5.19%)	4 / 79 (5.06%)	5 / 78 (6.41%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	2 / 18 (11.11%)	1 / 17 (5.88%)	0 / 19 (0.00%)	3 / 21 (14.29%)	1 / 18 (5.56%)	1 / 20 (5.00%)	6 / 73 (8.22%)	2 / 27 (7.41%)	1 / 41 (2.44%)	3 / 28 (10.71%)	5 / 34 (14.71%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	2	5	5	4	5	1	0	0	1	2	1	0	3	2	1	7	3	2	3	6	2	2
Osteochondritis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Osteosclerosis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0	0	1	0	0	0
Pain In Extremity
subjects affected / exposed	10 / 83 (12.05%)	8 / 82 (9.76%)	8 / 77 (10.39%)	11 / 79 (13.92%)	3 / 78 (3.85%)	1 / 19 (5.26%)	3 / 22 (13.64%)	1 / 18 (5.56%)	2 / 17 (11.76%)	3 / 18 (16.67%)	1 / 17 (5.88%)	3 / 19 (15.79%)	2 / 21 (9.52%)	1 / 18 (5.56%)	0 / 20 (0.00%)	12 / 73 (16.44%)	4 / 27 (14.81%)	2 / 41 (4.88%)	6 / 28 (21.43%)	1 / 34 (2.94%)	2 / 23 (8.70%)	7 / 32 (21.88%)
occurrences all number	13	10	8	11	5	1	4	1	2	3	1	4	2	1	0	15	5	2	6	1	3	9
Polyarthritis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Rotator Cuff Syndrome
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	3 / 77 (3.90%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	5	1	0	0	0	0	1	1	0	0	0	0	0	2	0	1	0	0	0	0
Sacroiliitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Synovial Cyst
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	1	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	1
Tendonitis
subjects affected / exposed	1 / 83 (1.20%)	6 / 82 (7.32%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	2 / 28 (7.14%)	3 / 34 (8.82%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	1	6	0	1	0	0	1	0	0	1	0	0	0	0	1	1	0	0	2	3	2	2
Torticollis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	2 / 28 (7.14%)	3 / 34 (8.82%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	2	3	2	2
Infections and infestations
Bacterial Infection
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	2 / 83 (2.41%)	4 / 82 (4.88%)	4 / 77 (5.19%)	2 / 79 (2.53%)	1 / 78 (1.28%)	1 / 19 (5.26%)	2 / 22 (9.09%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 19 (5.26%)	1 / 21 (4.76%)	1 / 18 (5.56%)	0 / 20 (0.00%)	4 / 73 (5.48%)	4 / 27 (14.81%)	4 / 41 (9.76%)	3 / 28 (10.71%)	5 / 34 (14.71%)	5 / 23 (21.74%)	5 / 32 (15.63%)
occurrences all number	5	6	5	2	2	1	3	1	0	0	3	1	1	1	0	7	4	4	4	5	9	5
Cellulitis
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0
Chronic Sinusitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	1 / 83 (1.20%)	6 / 82 (7.32%)	3 / 77 (3.90%)	1 / 79 (1.27%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	1 / 21 (4.76%)	0 / 18 (0.00%)	2 / 20 (10.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	1 / 28 (3.57%)	0 / 34 (0.00%)	2 / 23 (8.70%)	0 / 32 (0.00%)
occurrences all number	3	6	3	2	2	0	0	0	0	0	0	1	1	0	2	0	0	1	1	0	2	0
Ear Infection
subjects affected / exposed	0 / 83 (0.00%)	2 / 82 (2.44%)	1 / 77 (1.30%)	1 / 79 (1.27%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	4	1	1	2	0	0	0	0	0	0	1	1	0	0	1	0	0	1	2	0	1
Fungal Infection
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Furuncle
subjects affected / exposed	1 / 83 (1.20%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Gastroenteritis
subjects affected / exposed	3 / 83 (3.61%)	2 / 82 (2.44%)	1 / 77 (1.30%)	4 / 79 (5.06%)	1 / 78 (1.28%)	0 / 19 (0.00%)	1 / 22 (4.55%)	2 / 18 (11.11%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 18 (5.56%)	0 / 20 (0.00%)	2 / 73 (2.74%)	2 / 27 (7.41%)	0 / 41 (0.00%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	4	3	1	4	1	0	1	2	0	1	1	0	1	1	0	2	2	0	0	1	1	1
Herpes Zoster
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	1 / 77 (1.30%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	1	2	1	0
Influenza
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	1 / 77 (1.30%)	2 / 79 (2.53%)	3 / 78 (3.85%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 21 (9.52%)	0 / 18 (0.00%)	0 / 20 (0.00%)	4 / 73 (5.48%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	4 / 34 (11.76%)	0 / 23 (0.00%)	5 / 32 (15.63%)
occurrences all number	1	3	1	2	3	0	0	1	0	1	0	0	2	0	0	4	0	0	1	4	0	7
Nasal Abscess
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	14 / 83 (16.87%)	9 / 82 (10.98%)	16 / 77 (20.78%)	8 / 79 (10.13%)	14 / 78 (17.95%)	1 / 19 (5.26%)	4 / 22 (18.18%)	2 / 18 (11.11%)	2 / 17 (11.76%)	3 / 18 (16.67%)	0 / 17 (0.00%)	2 / 19 (10.53%)	3 / 21 (14.29%)	1 / 18 (5.56%)	1 / 20 (5.00%)	13 / 73 (17.81%)	6 / 27 (22.22%)	10 / 41 (24.39%)	7 / 28 (25.00%)	8 / 34 (23.53%)	5 / 23 (21.74%)	9 / 32 (28.13%)
occurrences all number	20	13	20	10	23	1	5	3	2	3	0	2	3	1	2	16	13	13	9	15	9	20
Onychomycosis
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	1 / 77 (1.30%)	0 / 79 (0.00%)	1 / 78 (1.28%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	2 / 73 (2.74%)	1 / 27 (3.70%)	0 / 41 (0.00%)	0 / 28 (0.00%)	2 / 34 (5.88%)	3 / 23 (13.04%)	1 / 32 (3.13%)
occurrences all number	0	1	1	0	1	2	1	0	0	0	0	0	0	0	1	2	1	0	0	3	4	2
Oral Candidiasis
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	1	0	2	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	1
Oral Herpes
subjects affected / exposed	1 / 83 (1.20%)	2 / 82 (2.44%)	0 / 77 (0.00%)	2 / 79 (2.53%)	2 / 78 (2.56%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	1 / 20 (5.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 41 (0.00%)	2 / 28 (7.14%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	1	2	0	2	5	0	0	0	0	0	0	0	0	1	0	2	0	0	2	1	0	2
Otitis Media Acute
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0
Pharyngitis
subjects affected / exposed	4 / 83 (4.82%)	2 / 82 (2.44%)	4 / 77 (5.19%)	2 / 79 (2.53%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	2 / 19 (10.53%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	4	2	4	2	0	0	0	0	0	0	0	2	1	0	0	1	0	1	0	0	2	1
Pharyngitis Streptococcal
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	3 / 32 (9.38%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	3	1	4
Pneumonia
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	2 / 41 (4.88%)	0 / 28 (0.00%)	1 / 34 (2.94%)	1 / 23 (4.35%)	3 / 32 (9.38%)
occurrences all number	0	0	1	1	1	0	0	0	1	0	0	1	0	0	0	1	1	3	0	3	1	4
Pyoderma
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory Tract Infection
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	1 / 23 (4.35%)	0 / 32 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	2	0	0	0	0	0	0	0	0	0	1	0	2	0
Respiratory Tract Infection Viral
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 77 (1.30%)	0 / 79 (0.00%)	1 / 78 (1.28%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	1 / 77 (1.30%)	1 / 79 (1.27%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	2 / 34 (5.88%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	3	1	1	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1	2	0	0
Sinusitis
subjects affected / exposed	4 / 83 (4.82%)	4 / 82 (4.88%)	5 / 77 (6.49%)	4 / 79 (5.06%)	5 / 78 (6.41%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	2 / 18 (11.11%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	3 / 73 (4.11%)	3 / 27 (11.11%)	2 / 41 (4.88%)	1 / 28 (3.57%)	1 / 34 (2.94%)	4 / 23 (17.39%)	0 / 32 (0.00%)
occurrences all number	4	4	6	5	6	0	0	2	1	2	0	1	0	0	0	3	5	2	2	1	4	0
Tooth Abscess
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	2 / 77 (2.60%)	2 / 79 (2.53%)	3 / 78 (3.85%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 18 (5.56%)	0 / 20 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	1 / 41 (2.44%)	0 / 28 (0.00%)	0 / 34 (0.00%)	1 / 23 (4.35%)	1 / 32 (3.13%)
occurrences all number	1	0	2	2	3	0	1	0	0	1	0	0	0	1	0	1	0	1	0	0	1	1
Tooth Infection
subjects affected / exposed	0 / 83 (0.00%)	0 / 82 (0.00%)	2 / 77 (2.60%)	3 / 79 (3.80%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	0	0	2	3	0	0	0	0	1	1	0	0	0	0	1	0	0	0	0	0	0	1
Upper Respiratory Tract Infection
subjects affected / exposed	9 / 83 (10.84%)	10 / 82 (12.20%)	7 / 77 (9.09%)	7 / 79 (8.86%)	10 / 78 (12.82%)	1 / 19 (5.26%)	0 / 22 (0.00%)	3 / 18 (16.67%)	2 / 17 (11.76%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 21 (9.52%)	0 / 18 (0.00%)	0 / 20 (0.00%)	3 / 73 (4.11%)	0 / 27 (0.00%)	1 / 41 (2.44%)	2 / 28 (7.14%)	3 / 34 (8.82%)	2 / 23 (8.70%)	2 / 32 (6.25%)
occurrences all number	11	12	9	11	14	1	0	4	2	1	0	0	3	0	0	4	0	1	7	5	2	2
Urinary Tract Infection
subjects affected / exposed	11 / 83 (13.25%)	6 / 82 (7.32%)	7 / 77 (9.09%)	8 / 79 (10.13%)	12 / 78 (15.38%)	1 / 19 (5.26%)	2 / 22 (9.09%)	1 / 18 (5.56%)	2 / 17 (11.76%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	3 / 21 (14.29%)	0 / 18 (0.00%)	2 / 20 (10.00%)	10 / 73 (13.70%)	4 / 27 (14.81%)	2 / 41 (4.88%)	9 / 28 (32.14%)	9 / 34 (26.47%)	6 / 23 (26.09%)	7 / 32 (21.88%)
occurrences all number	17	7	7	10	15	1	3	1	2	0	0	0	3	0	3	12	4	3	15	19	20	15
Viral Infection
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	4 / 79 (5.06%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	1 / 27 (3.70%)	0 / 41 (0.00%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	1 / 32 (3.13%)
occurrences all number	2	0	0	4	0	0	0	0	0	0	1	0	0	0	0	2	1	0	1	1	0	1
Viral Upper Respiratory Tract Infection
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye infection
subjects affected / exposed	1 / 83 (1.20%)	0 / 82 (0.00%)	0 / 77 (0.00%)	2 / 79 (2.53%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 41 (0.00%)	0 / 28 (0.00%)	0 / 34 (0.00%)	0 / 23 (0.00%)	2 / 32 (6.25%)
occurrences all number	1	0	0	2	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	2
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 18 (0.00%)	1 / 20 (5.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 41 (2.44%)	1 / 28 (3.57%)	1 / 34 (2.94%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	1	1	1	0	0
Hypercholesterolaemia
subjects affected / exposed	1 / 83 (1.20%)	3 / 82 (3.66%)	1 / 77 (1.30%)	3 / 79 (3.80%)	0 / 78 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 18 (11.11%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 18 (0.00%)	0 / 20 (0.00%)	2 / 73 (2.74%)	2 / 27 (7.41%)	0 / 41 (0.00%)	3 / 28 (10.71%)	1 / 34 (2.94%)	1 / 23 (4.35%)	4 / 32 (12.50%)
occurrences all number	1	3	1	3	0	0	0	2	0	0	0	0	1	0	0	2	2	0	3	1	1	4
Hyperlipidaemia
subjects affected / exposed	0 / 83 (0.00%)	1 / 82 (1.22%)	0 / 77 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 18 (0.00%)	0 / 20 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 41 (0.00%)	1 / 28 (3.57%)	0 / 34 (0.00%)	0 / 23 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

26 Jun 2006

AM1. The primary reason for this amendment was a revision to the protocol synopsis, in particular the data analysis section.

22 May 2007

EXT1/004-10. The primary reason for this amendment was to add a 12-month extension to the previous protocol (Protocol 004-01).

22 Jun 2007

AM2. The primary reason for this amendment was to add an 18-month interim analysis (Protocol 004-02).

03 Apr 2008

EXT1,AM1/004-11. The primary reason for this amendment was to add preliminary information on the predicted magnetic resonance imaging (MRI) findings suggestive of metaphyseal fibrosis in the ongoing growing monkey toxicology study at 10-fold preclinical/clinical margins, along with information on the absence of such findings at 12-fold preclinical/clinical margins in aged dogs.

03 Jun 2008

EXT2/004-20. The primary reason for this amendment was to add a 24-month extension to the previous protocol (Protocol 004-11).

11 Dec 2008

EXT2,AM1/004-21. The primary reason for this amendment was to add supplementary bone mineral density (BMD) scans at Visits 21 and 25 (Months 42 and 54) for additional efficacy measurements.

17 Feb 2010

EXT2,AM2/004-22. The primary reason for this amendment was to issue a revised definition of overdose for odanacatib to the following: Ingesting two or more tablets of study drug within a 5-day period.

25 May 2010

EXT3/004-30. The primary reason for this amendment was to add a 5-year extension to the previous protocol (Protocol 004-22).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

Primary: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 24 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 24 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 36 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 36 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 120 Months

Primary: Percentage Change From Baseline in Lumbar Spine BMD at 120 Months

Primary: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)

Primary: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)

Primary: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)

Primary: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)

Secondary: Percentage Change From Baseline in Total Hip BMD at 12 Months

Secondary: Percentage Change From Baseline in Total Hip BMD at 12 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 12 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 12 Months

Secondary: Percentage Change From Baseline in Trochanter BMD at 12 Months

Secondary: Percentage Change From Baseline in Trochanter BMD at 12 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 12 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 12 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 12 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months

Secondary: Percentage Change From Baseline in Total Hip BMD at 24 Months

Secondary: Percentage Change From Baseline in Total Hip BMD at 24 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 24 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 24 Months

Secondary: Percentage Change From Baseline in Tronchanter BMD at 24 Months

Secondary: Percentage Change From Baseline in Tronchanter BMD at 24 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 24 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 24 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 24 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 24 Months

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 24 Months

Secondary: Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months

Secondary: Percentage Change From Baseline in Total Hip BMD at 36 Months

Secondary: Percentage Change From Baseline in Total Hip BMD at 36 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 36 Months

Secondary: Percentage Change From Baseline in Femoral Neck BMD at 36 Months

Secondary: Percentage Change From Baseline in Trochanter BMD at 36 Months

Secondary: Percentage Change From Baseline in Trochanter BMD at 36 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 36 Months

Secondary: Percentage Change From Baseline in Total Body BMD at 36 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 36 Months

Secondary: Percentage Change From Baseline in Distal Forearm BMD at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months

Secondary: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months