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Clinical Trial Results:
A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study To Assess The Efficacy, Long-Term Safety And Tolerability Of PF-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events

Summary
EudraCT number	2013-002643-28
Trial protocol	LT GB ES HU
Global end of trial date	10 Jul 2017

Results information
Results version number	v2(current)
This version publication date	22 Jul 2018
First version publication date	08 Jul 2017
Other versions	v1
Version creation reason

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

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Trial information

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Sponsor protocol code

B1481020

ISRCTN number

US NCT number

NCT01968967

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

ClinicalTrials.gov Call Center, Pfizer, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

ClinicalTrials.gov Call Center, Pfizer, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.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

25 Oct 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Jul 2017

Was the trial ended prematurely?

Main objective of the trial

To demonstrate a superior low-density lipoprotein cholesterol (LDL-C) lowering effect of Bococizumab 150 milligram (mg) administered by the subcutaneous (SC) route every 14 days (Q14D) compared to placebo, in subjects with primary hyperlipidemia or mixed dyslipidemia at high and very high risk for cardiovascular events receiving a maximally tolerated dose of statin therapy.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Oct 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 55

Country: Number of subjects enrolled

Colombia: 53

Country: Number of subjects enrolled

Hungary: 70

Country: Number of subjects enrolled

Lithuania: 19

Country: Number of subjects enrolled

Mexico: 69

Country: Number of subjects enrolled

Romania: 57

Country: Number of subjects enrolled

Russian Federation: 30

Country: Number of subjects enrolled

Spain: 80

Country: Number of subjects enrolled

Taiwan: 14

Country: Number of subjects enrolled

United Kingdom: 185

Country: Number of subjects enrolled

United States: 1475

Country: Number of subjects enrolled

France: 32

Worldwide total number of subjects

2139

EEA total number of subjects

443

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)

1250

From 65 to 84 years

875

85 years and over

Subject disposition

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Recruitment details

Screening details

This study was conducted at multiple sites from 28 October 2014 to 15 July 2016 for the Treatment Period and up to 10 July 2017 for the Extension Period.

Period 1 title

Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo (Treatment Period)

Arm description

Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks over a period of 52 weeks.

Bococizumab 150 mg (Treatment Period)

Arm description

Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Arm type

Experimental

Investigational medicinal product name

PF-04950615

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks over a period of 52 weeks.

Number of subjects in period 1	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Started	1071	1068
Completed	925	934
Not completed	146	134
Consent withdrawn by subject	71	61
Did Not Meet Entrance Criteria	2	3
Death	9	2
Adverse event	9	8
Randomized Not Treated	6	5
Unspecified	22	22
Lost to follow-up	26	31
Protocol deviation	1	2

Period 2 title

Extension Period

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo (Extension Period)

Arm description

Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Bococizumab ADA positive (Extension Period)

Arm description

Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, subjects who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 [log2] units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Bococizumab ADA negative (Extension Period)

Arm description

Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Subjects who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2 ^[1]	Placebo (Extension Period)	Bococizumab ADA positive (Extension Period)	Bococizumab ADA negative (Extension Period)
Started	47	19	39
Completed	45	19	34
Not completed	2	0	5
Consent withdrawn by subject	2	-	5

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: Only subjects who consented for extension period were followed in extension period.

Baseline characteristics

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Reporting group title

Placebo (Treatment Period)

Reporting group description

Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Reporting group title

Bococizumab 150 mg (Treatment Period)

Reporting group description

Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Reporting group values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)	Total
Number of subjects	1071	1068	2139
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	618	632	1250
From 65-84 years	443	432	875
85 years and over	10	4	14
Age Continuous
Units: years
arithmetic mean (standard deviation)	62.2 ( 9.8 )	61.8 ( 9.3 )	-
Gender, Male/Female
Units: Subjects
Female	434	434	868
Male	637	634	1271

End points

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Reporting group title

Placebo (Treatment Period)

Reporting group description

Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Reporting group title

Bococizumab 150 mg (Treatment Period)

Reporting group description

Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

Reporting group title

Placebo (Extension Period)

Reporting group description

Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110.

Reporting group title

Bococizumab ADA positive (Extension Period)

Reporting group description

Reporting group title

Bococizumab ADA negative (Extension Period)

Reporting group description

Primary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

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End point title

Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

End point description

Full analysis set (FAS) included all subjects who were randomized. Here, "Number of subjects analyzed (N)" signifies number of subjects who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	994	980
Units: percent change
arithmetic mean (standard deviation)	1 ( 22.5 )	-54.9 ( 26.84 )

PF-04950615 150 mg Versus (vs) Placebo

Statistical analysis description

Least square (LS) mean difference and associated 95 percent (%) confidence interval (CI), and p-value were derived from mixed effect model repeat measurement (MMRM) model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

1974

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-56.2

Confidence interval

level

95%

sides

2-sided

lower limit

-58.3

upper limit

-54

Variability estimate

Standard error of the mean

Dispersion value

1.1

Secondary: Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52

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End point title

Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =997, 981)	-0.1 ( 16.18 )	-34.9 ( 18.34 )
Week 24 (n =988, 988)	1 ( 18.68 )	-30.5 ( 21.56 )
Week 52 (n =920, 932)	-0.3 ( 18.75 )	-25.3 ( 23.43 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-35

Confidence interval

level

95%

sides

2-sided

lower limit

-36.5

upper limit

-33.5

Variability estimate

Standard error of the mean

Dispersion value

0.76

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-31.6

Confidence interval

level

95%

sides

2-sided

lower limit

-33.3

upper limit

-29.8

Variability estimate

Standard error of the mean

Dispersion value

0.89

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-24.7

Confidence interval

level

95%

sides

2-sided

lower limit

-26.6

upper limit

-22.8

Variability estimate

Standard error of the mean

Dispersion value

0.96

Secondary: Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52

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End point title

Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =994, 978)	0.4 ( 18.83 )	-50.4 ( 27.42 )
Week 24 (n =987, 988)	1.5 ( 21.43 )	-44.9 ( 31.17 )
Week 52 (n =915, 929)	-0.4 ( 21.78 )	-37.4 ( 32.92 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-50.8

Confidence interval

level

95%

sides

2-sided

lower limit

-52.9

upper limit

-48.8

Variability estimate

Standard error of the mean

Dispersion value

1.04

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-46.1

Confidence interval

level

95%

sides

2-sided

lower limit

-48.5

upper limit

-43.8

Variability estimate

Standard error of the mean

Dispersion value

1.19

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-36.1

Confidence interval

level

95%

sides

2-sided

lower limit

-38.6

upper limit

-33.6

Variability estimate

Standard error of the mean

Dispersion value

1.28

Secondary: Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52

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End point title

Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =996, 980)	0.2 ( 21.22 )	-49.7 ( 25.51 )
Week 24 (n =987, 987)	1.6 ( 24.65 )	-43.8 ( 30.02 )
Week 52 (n =919, 932)	-0.3 ( 24.62 )	-36.8 ( 32.73 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-50.1

Confidence interval

level

95%

sides

2-sided

lower limit

-52.1

upper limit

-48

Variability estimate

Standard error of the mean

Dispersion value

1.04

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-45.5

Confidence interval

level

95%

sides

2-sided

lower limit

-47.9

upper limit

-43.1

Variability estimate

Standard error of the mean

Dispersion value

1.22

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-35.9

Confidence interval

level

95%

sides

2-sided

lower limit

-38.5

upper limit

-33.3

Variability estimate

Standard error of the mean

Dispersion value

1.33

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

End point description

A subset of FAS included all subjects who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of subjects evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	791	788
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =734, 725)	1.9 ( 23.07 )	-55.6 ( 26.81 )
Week 24 (n =730, 729)	3.9 ( 27.17 )	-49.2 ( 32.58 )
Week 52 (n =683, 688)	3.2 ( 26.65 )	-40.6 ( 36.45 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

1579

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-57.7

Confidence interval

level

95%

sides

2-sided

lower limit

-60.2

upper limit

-55.2

Variability estimate

Standard error of the mean

Dispersion value

1.29

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

1579

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-53.1

Confidence interval

level

95%

sides

2-sided

lower limit

-56.1

upper limit

-50

Variability estimate

Standard error of the mean

Dispersion value

1.55

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

1579

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-42.8

Confidence interval

level

95%

sides

2-sided

lower limit

-46.2

upper limit

-39.5

Variability estimate

Standard error of the mean

Dispersion value

1.7

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

End point description

A subset of FAS included all subjects who were randomized and had TG >=200 mg/dL at pre-randomization. Here, "n" signifies number of subjects evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	280	280
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =260, 255)	-1.5 ( 20.82 )	-53 ( 26.9 )
Week 24 (n =257, 260)	1.1 ( 28.21 )	-42.8 ( 31.87 )
Week 52 (n =237, 241)	-1.2 ( 27.78 )	-36.3 ( 34.88 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

560

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-51.8

Confidence interval

level

95%

sides

2-sided

lower limit

-55.9

upper limit

-47.7

Variability estimate

Standard error of the mean

Dispersion value

2.09

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

560

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-44

Confidence interval

level

95%

sides

2-sided

lower limit

-49.1

upper limit

-38.8

Variability estimate

Standard error of the mean

Dispersion value

2.61

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

560

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-34.6

Confidence interval

level

95%

sides

2-sided

lower limit

-40.2

upper limit

-29

Variability estimate

Standard error of the mean

Dispersion value

2.83

Secondary: Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52

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End point title

Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =994, 975)	2.4 ( 85.08 )	-26.3 ( 42.63 )
Week 24 (n =984, 983)	8.7 ( 146 )	-22.7 ( 51.48 )
Week 52 (n =918, 927)	4.3 ( 139.49 )	-20.9 ( 110.14 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

-28.5

Confidence interval

level

95%

sides

2-sided

lower limit

-34.4

upper limit

-22.5

Variability estimate

Standard error of the mean

Dispersion value

3.04

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-25.3

Confidence interval

level

95%

sides

2-sided

lower limit

-36.8

upper limit

-13.7

Variability estimate

Standard error of the mean

Dispersion value

5.89

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-31.1

Confidence interval

level

95%

sides

2-sided

lower limit

-40.6

upper limit

-21.5

Variability estimate

Standard error of the mean

Dispersion value

4.86

Secondary: Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =996, 981)	0.4 ( 13.92 )	6.2 ( 14.99 )
Week 24 (n =987, 987)	0.5 ( 15.25 )	6.1 ( 15.32 )
Week 52 (n =919, 932)	1.2 ( 16.09 )	6.5 ( 17.87 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

LS Mean Difference

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.63

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

6.8

Variability estimate

Standard error of the mean

Dispersion value

0.67

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

3.7

upper limit

6.7

Variability estimate

Standard error of the mean

Dispersion value

0.76

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period

Top of page

End point title

Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 24 (n =987, 989)	3.2 ( 27.45 )	-47.5 ( 32.5 )
Week 52 (n =920, 929)	2.1 ( 27 )	-39.5 ( 36.08 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-50.7

Confidence interval

level

95%

sides

2-sided

lower limit

-53.3

upper limit

-48

Variability estimate

Standard error of the mean

Dispersion value

1.34

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-40.7

Confidence interval

level

95%

sides

2-sided

lower limit

-43.5

upper limit

-37.8

Variability estimate

Standard error of the mean

Dispersion value

1.46

Secondary: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =997, 981)	3.5 ( 38.25 )	-12.9 ( 39.99 )
Week 24 (n =988, 988)	5.1 ( 51.06 )	-11.5 ( 41.33 )
Week 52 (n =920, 932)	0.3 ( 43.63 )	-12.5 ( 40.82 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-16.6

Confidence interval

level

95%

sides

2-sided

lower limit

-20

upper limit

-13.2

Variability estimate

Standard error of the mean

Dispersion value

1.73

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-16.7

Confidence interval

level

95%

sides

2-sided

lower limit

-20.7

upper limit

-12.6

Variability estimate

Standard error of the mean

Dispersion value

2.05

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16.5

upper limit

-9

Variability estimate

Standard error of the mean

Dispersion value

1.91

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =995, 980)	-0.6 ( 11.22 )	2.8 ( 11.73 )
Week 24 (n =987, 988)	-0.9 ( 12.1 )	2.7 ( 11.93 )
Week 52 (n =916, 929)	-1.2 ( 12.34 )	2.6 ( 13.75 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

4.3

Variability estimate

Standard error of the mean

Dispersion value

0.49

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

4.5

Variability estimate

Standard error of the mean

Dispersion value

0.51

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

4.9

Variability estimate

Standard error of the mean

Dispersion value

0.57

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =993, 972)	-1.2 ( 13.05 )	-1 ( 13.75 )
Week 24 (n =986, 986)	-0.9 ( 13.56 )	0.1 ( 14.28 )
Week 52 (n =916, 928)	-2.5 ( 13.5 )	-1 ( 13.72 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.59

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

2.3

Variability estimate

Standard error of the mean

Dispersion value

0.61

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

2.7

Variability estimate

Standard error of the mean

Dispersion value

0.61

Secondary: Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52

Top of page

End point title

Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percent change
arithmetic mean (standard deviation)
Week 12 (n =997, 981)	3.5 ( 38.25 )	-12.9 ( 39.99 )
Week 24 (n =988, 988)	5.1 ( 51.06 )	-11.5 ( 41.33 )
Week 52 (n =920, 932)	0.3 ( 43.63 )	-12.5 ( 40.82 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-16.6

Confidence interval

level

95%

sides

2-sided

lower limit

-20

upper limit

-13.2

Variability estimate

Standard error of the mean

Dispersion value

1.73

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-16.7

Confidence interval

level

95%

sides

2-sided

lower limit

-20.7

upper limit

-12.6

Variability estimate

Standard error of the mean

Dispersion value

2.05

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16.5

upper limit

-9

Variability estimate

Standard error of the mean

Dispersion value

1.91

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12

End point description

A subset of FAS included all subjects who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of subjects evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	791	788
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =791, 787)	109.1 ( 33.24 )	107.1 ( 30.43 )
Change at Week 12 (n =734, 725)	0.3 ( 25.7 )	-59.3 ( 32.3 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

1579

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-60.4

Confidence interval

level

95%

sides

2-sided

lower limit

-63.1

upper limit

-57.6

Variability estimate

Standard error of the mean

Dispersion value

1.4

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12

End point description

A subset of FAS included all subjects who were randomized and had TG >=200 mg/dL at pre-randomization. Here, "n" signifies number of subjects evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	280	280
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =280, 280)	125.9 ( 40.08 )	121.5 ( 37.84 )
Change at Week 12 (n =260, 255)	-3.4 ( 29.08 )	-64.8 ( 38.94 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

560

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-62.8

Confidence interval

level

95%

sides

2-sided

lower limit

-68.3

upper limit

-57.3

Variability estimate

Standard error of the mean

Dispersion value

2.8

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1071, 1067)	113.5 ( 35.9 )	110.9 ( 33.13 )
Change at Week 12 (n =994, 980)	-0.7 ( 26.66 )	-60.7 ( 34.22 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-61

Confidence interval

level

95%

sides

2-sided

lower limit

-63.5

upper limit

-58.5

Variability estimate

Standard error of the mean

Dispersion value

1.27

Secondary: Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1071, 1067)	186.3 ( 40.77 )	183.1 ( 38.31 )
Change at Week 12 (n =997, 981)	-1.8 ( 31.62 )	-64.5 ( 38.01 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-63.7

Confidence interval

level

95%

sides

2-sided

lower limit

-66.6

upper limit

-60.9

Variability estimate

Standard error of the mean

Dispersion value

1.46

Secondary: Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1071, 1066)	138 ( 39.67 )	135.3 ( 36.85 )
Change at Week 12 (n =996, 980)	-1.6 ( 30.93 )	-67 ( 38.89 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-66.4

Confidence interval

level

95%

sides

2-sided

lower limit

-69.3

upper limit

-63.6

Variability estimate

Standard error of the mean

Dispersion value

1.46

Secondary: Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1070, 1067)	94 ( 24.26 )	92.3 ( 22.74 )
Change at Week 12 (n =994, 978)	-0.7 ( 18.35 )	-46 ( 26.58 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-45.8

Confidence interval

level

95%

sides

2-sided

lower limit

-47.7

upper limit

-43.9

Variability estimate

Standard error of the mean

Dispersion value

0.97

Secondary: Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1069, 1063)	45.3 ( 49.77 )	46.4 ( 55.57 )
Change at Week 12 (n =994, 975)	0 ( 12.07 )	-10.6 ( 18.36 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-10.6

Confidence interval

level

95%

sides

2-sided

lower limit

-11.8

upper limit

-9.3

Variability estimate

Standard error of the mean

Dispersion value

0.63

Secondary: Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Top of page

End point title

Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: mg/dL
arithmetic mean (standard deviation)
Baseline (n =1071, 1066)	48.3 ( 12.42 )	47.8 ( 12.72 )
Change at Week 12 (n =996, 981)	-0.1 ( 6.84 )	2.5 ( 7.07 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

3.3

Variability estimate

Standard error of the mean

Dispersion value

0.31

Secondary: Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Top of page

End point title

Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: Ratio
arithmetic mean (standard deviation)
Baseline (n =1071, 1066)	4.1 ( 1.22 )	4 ( 1.19 )
Change at Week 12 (n =996, 980)	0 ( 0.86 )	-1.5 ( 1.09 )
Change at Week 24 (n =987, 987)	0 ( 0.96 )	-1.4 ( 1.15 )
Change at Week 52 (n =919, 932)	0 ( 0.97 )	-1.1 ( 1.21 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

-1.5

Variability estimate

Standard error of the mean

Dispersion value

0.04

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

-1.3

Variability estimate

Standard error of the mean

Dispersion value

0.05

PF-04950615 150 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.05

Secondary: Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

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End point title

Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: Ratio
arithmetic mean (standard deviation)
Baseline (n =1070, 1067)	0.7 ( 0.21 )	0.7 ( 0.2 )
Change at Week 12 (n =994, 978)	0 ( 0.14 )	-0.3 ( 0.21 )
Change at Week 24 (n =987, 988)	0 ( 0.15 )	-0.3 ( 0.23 )
Change at Week 52 (n =915, 929)	0 ( 0.16 )	-0.2 ( 0.23 )

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.01

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.01

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.01

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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End point title

Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percentage of subjects
number (not applicable)
Week 12 (n =994, 980)	45.3	90.9
Week 24 (n =987, 990)	43.2	85.8
Week 52 (n =920, 930)	45	79.8

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

19.21

upper limit

38.02

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

6.3

Confidence interval

level

95%

sides

2-sided

lower limit

4.99

upper limit

8.06

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

9.84

upper limit

16.86

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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End point title

Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

End point description

FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.

End point type

Secondary

End point timeframe

Week 12, 24, 52

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1071	1068
Units: percentage of subjects
number (not applicable)
Week 12 (n =994, 980)	5.9	78.6
Week 24 (n =987, 990)	7.8	69.8
Week 52 (n =920, 930)	6.8	61.4

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

86.5

Confidence interval

level

95%

sides

2-sided

lower limit

61.74

upper limit

121.25

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

35.9

Confidence interval

level

95%

sides

2-sided

lower limit

26.83

upper limit

47.96

PF-04950615 150 mg vs Placebo

Statistical analysis description

Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.

Comparison groups

Placebo (Treatment Period) v Bococizumab 150 mg (Treatment Period)

Number of subjects included in analysis

2139

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

25.5

Confidence interval

level

95%

sides

2-sided

lower limit

18.9

upper limit

34.47

Secondary: Plasma Concentration of PF-04950615 at Week 12, 24 and 52

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End point title

Plasma Concentration of PF-04950615 at Week 12, 24 and 52 ^[1]

End point description

Plasma concentration of PF-04950615 at Week 12, 24 and 52 was reported. Analysis set included subjects who received at least 1 dose of PF-04950615. Here, "n" signifies those subjects who were evaluable at specified time points.

End point type

Secondary

End point timeframe

Week 12, 24, 52

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed only for reporting arm: Bococizumab (PF-04950615) 150 mg (Treatment Period).

End point values	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1063
Units: Microgram per milliliter
arithmetic mean (standard deviation)
Week 12 (n= 996)	4.91 ( 4.987 )
Week 24 (n= 975)	4.74 ( 5.772 )
Week 52 (n= 915)	3.6 ( 4.685 )

No statistical analyses for this end point

Secondary: Number of Subjects With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions

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End point title

Number of Subjects With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions

End point description

Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia’s, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Subjects with type 1 or type 3 hypersensitivity reactions and subjects with injection site reactions were reported in this outcome measure. Safety analysis population. Here, "n" signifies those subjects who were evaluable at specified time points for each reporting arm respectively.

End point type

Secondary

End point timeframe

Baseline up to Week 58

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	1065	1063
Units: subjects
Type 1 or 3 hypersensitivity reactions	2	2
Injection site reactions	56	144

No statistical analyses for this end point

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb):Treatment Period

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End point title

Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb):Treatment Period

End point description

Percentage of subjects with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log2) unit was considered to be ADA positive and nAb titer >=1.58 (log2) unit was considered to be nAb positive. Safety analysis population included all subjects who received at least 1 dose of study treatment. Here, "N" signifies those subjects who were evaluable for this endpoint for each reporting arm respectively.

End point type

Secondary

End point timeframe

Baseline up to Week 58

End point values	Placebo (Treatment Period)	Bococizumab 150 mg (Treatment Period)
Number of subjects analysed	231	1046
Units: Percentage of subjects
number (not applicable)
ADA (n= 231, 1046)	0.9	46.7
nAb (n= 231, 1046)	0.4	30.3

No statistical analyses for this end point

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period

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End point title

Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period

End point description

Percentage of subjects with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log2) unit was considered to be ADA positive and nAb titer >=1.58 (log2) unit was considered to be nAb positive. All subjects who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms Placebo (Extension period) and Bococizumab ADA negative (Extension period). Here, "n" signifies number of subjects who were evaluable at specified time points.

End point type

Secondary

End point timeframe

Week 58 follow-up visit, Week 71, Week 84, Week 97, Week 110

End point values	Bococizumab ADA positive (Extension Period)
Number of subjects analysed	19
Units: subjects
number (not applicable)
Week 58 follow-up visit ADA (n =19)	100.0
Week 58 follow-up visit nAb (n =19)	36.8
Week 71: ADA (n =16)	62.5
Week 71: nAb (n =16)	31.3
Week 84: ADA (n =11)	81.8
Week 84: nAb (n =11)	45.5
Week 97: ADA (n =4)	50.0
Week 97: nAb (n =4)	0.0
Week 110: ADA (n =7)	85.7
Week 110: nAb (n =7)	57.1

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 follow-up visit,, 71, 84, 97 and 110: Extension Period

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End point title

Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 follow-up visit,, 71, 84, 97 and 110: Extension Period

End point description

All subjects who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms Placebo (Extension period) and Bococizumab ADA negative (Extension period). Here, "n" signifies number of subjects who were evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 58 follow-up visit, 71, 84, 97, 110

End point values	Bococizumab ADA positive (Extension Period)
Number of subjects analysed	19
Units: Percent change
arithmetic mean (standard deviation)
Week 58 follow-up visit (n =19)	-6.4 ( 24.67 )
Week 71 (n =16)	-10.4 ( 41.51 )
Week 84 (n =11)	-15.8 ( 25.65 )
Week 97 (n =9)	-20.8 ( 31.08 )
Week 110 (n =9)	-5.0 ( 28.65 )

No statistical analyses for this end point

Secondary: Number of Subjects who Changed Concomitant Medications During Extension Period

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End point title

Number of Subjects who Changed Concomitant Medications During Extension Period

End point description

In this endpoint total number of subjects who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported. All subjects who consented for extension period.

End point type

Secondary

End point timeframe

Week 58 follow-up visit to Week 110

End point values	Placebo (Extension Period)	Bococizumab ADA positive (Extension Period)	Bococizumab ADA negative (Extension Period)
Number of subjects analysed	47	19	39
Units: subjects	2	1	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

For SAEs: Baseline up to Week 110 and for other AEs: Baseline up to Week 58

Adverse event reporting additional description

Event may be serious in 1 subject and nonserious in other subject or 1 subject may have experienced SAE and non SAE. Subjects evaluable: treatment period: subjects who had received at least 1 dose of study drug; extension period: subjects who consented for extension period. Non serious AEs were not collected for extension period.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to 110 weeks.

Reporting group title

PF-04950615 150 mg

Reporting group description

Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to 110 weeks.

Reporting group title

Placebo (Extension Period)

Reporting group description

Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110.

Reporting group title

Bococizumab ADA positive (Extension Period)

Reporting group description

Reporting group title

Bococizumab ADA negative (Extension Period)

Reporting group description

Serious adverse events	Placebo	PF-04950615 150 mg	Placebo (Extension Period)	Bococizumab ADA positive (Extension Period)	Bococizumab ADA negative (Extension Period)
Total subjects affected by serious adverse events
subjects affected / exposed	150 / 1065 (14.08%)	116 / 1063 (10.91%)	1 / 47 (2.13%)	1 / 19 (5.26%)	1 / 39 (2.56%)
number of deaths (all causes)	9	2	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	2 / 1065 (0.19%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial adenocarcinoma
Additional description: This event was gender specific.
subjects affected / exposed ^[1]	0 / 430 (0.00%)	1 / 433 (0.23%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial cancer
Additional description: This event was gender specific.
subjects affected / exposed ^[2]	0 / 430 (0.00%)	1 / 433 (0.23%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric cancer
alternative assessment type: Systematic
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glioblastoma
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to spine
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastatic neoplasm
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cancer
Additional description: This event was gender specific.
subjects affected / exposed ^[3]	1 / 430 (0.23%)	0 / 433 (0.00%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
Additional description: This event was gender specific.‌
subjects affected / exposed ^[4]	3 / 635 (0.47%)	0 / 630 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Schwannoma
alternative assessment type: Systematic
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transitional cell carcinoma recurrent
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine cancer
Additional description: This event was gender specific.
subjects affected / exposed ^[5]	2 / 430 (0.47%)	0 / 433 (0.00%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
Additional description: This event was gender specific.
subjects affected / exposed ^[6]	0 / 430 (0.00%)	1 / 433 (0.23%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	4 / 1065 (0.38%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intermittent claudication
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	2 / 1065 (0.19%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Left leg - severe pain, redness, and induration
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	3 / 1065 (0.28%)	7 / 1063 (0.66%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 7	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral swelling
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Prostatic haemorrhage
Additional description: This event was gender specific.
subjects affected / exposed ^[7]	0 / 635 (0.00%)	1 / 630 (0.16%)	0 / 31 (0.00%)	0 / 8 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scrotal ulcer
Additional description: This event was gender specific.
subjects affected / exposed ^[8]	1 / 635 (0.16%)	0 / 630 (0.00%)	0 / 31 (0.00%)	0 / 8 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vaginal prolapse
Additional description: This event was gender specific.
subjects affected / exposed ^[9]	1 / 430 (0.23%)	0 / 433 (0.00%)	0 / 16 (0.00%)	0 / 11 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	3 / 1065 (0.28%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspiration
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	6 / 1065 (0.56%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
alternative dictionary used: MedDRA 20.0
subjects affected / exposed	0 / 1065 (0.00%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
alternative dictionary used: MedDRA 20.0
subjects affected / exposed	0 / 1065 (0.00%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism1
Additional description: Subjects in follow up period were evaluable.
alternative dictionary used: MedDRA 20.0
subjects affected / exposed	0 / 1065 (0.00%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 1065 (0.09%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug dependence
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Schizoaffective disorder
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood pressure increased
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood urine present
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram change
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Anastomotic ulcer haemorrhage
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Burns second degree
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	3 / 1065 (0.28%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laceration
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle injury
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nerve injury
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft occlusion
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft thrombosis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Bartter's syndrome
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 1065 (0.09%)	7 / 1063 (0.66%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 7	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	4 / 1065 (0.38%)	8 / 1063 (0.75%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 9	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	6 / 1065 (0.56%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve calcification
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arteriospasm coronary
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	4 / 1065 (0.38%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	3 / 1065 (0.28%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 6	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiorenal syndrome
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease1
subjects affected / exposed	4 / 1065 (0.38%)	3 / 1063 (0.28%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive heart disease
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 1065 (0.19%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	1 / 1065 (0.09%)	3 / 1063 (0.28%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subvalvular aortic stenosis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular extrasystoles
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 1065 (0.09%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 9
Coronary artery disease
alternative dictionary used: MedDRA 20.0
subjects affected / exposed	0 / 1065 (0.00%)	0 / 1063 (0.00%)	1 / 47 (2.13%)	1 / 19 (5.26%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Condition aggravated
alternative dictionary used: MedDRA 20.0
subjects affected / exposed	0 / 1065 (0.00%)	0 / 1063 (0.00%)	1 / 47 (2.13%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Carotid arteriosclerosis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	3 / 1065 (0.28%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cervical myelopathy
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lacunar infarction
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental impairment
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiculopathy
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 1065 (0.09%)	3 / 1063 (0.28%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	8 / 1065 (0.75%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 8	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Leukocytosis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	4 / 1065 (0.38%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal ulcer
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peptic ulcer haemorrhage
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Salivary gland calculus
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Volvulus
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jaundice cholestatic
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 1065 (0.19%)	3 / 1063 (0.28%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal mass
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	3 / 1065 (0.28%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cervical spinal stenosis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Costochondritis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc degeneration
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc disorder
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	3 / 1065 (0.28%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metatarsalgia
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neck mass
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 1065 (0.09%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal column stenosis
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Synovial cyst
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	2 / 1065 (0.19%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	2 / 1065 (0.19%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	5 / 1065 (0.47%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis of male external genital organ
Additional description: This event was gender specific.
subjects affected / exposed ^[10]	1 / 635 (0.16%)	0 / 630 (0.00%)	0 / 31 (0.00%)	0 / 8 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	2 / 1065 (0.19%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 1065 (0.09%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	3 / 1065 (0.28%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis externa
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	10 / 1065 (0.94%)	3 / 1063 (0.28%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 10	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scrotal abscess
Additional description: This event was gender specific.
subjects affected / exposed ^[11]	1 / 635 (0.16%)	0 / 630 (0.00%)	0 / 31 (0.00%)	0 / 8 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis syndrome
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 1065 (0.00%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Sialoadenitis
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin infection
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	3 / 1065 (0.28%)	4 / 1063 (0.38%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	2 / 1065 (0.19%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 1065 (0.09%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 1065 (0.09%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 1065 (0.09%)	0 / 1063 (0.00%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 1065 (0.09%)	2 / 1063 (0.19%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obesity
subjects affected / exposed	0 / 1065 (0.00%)	1 / 1063 (0.09%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event was gender specific.

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

Non-serious adverse events	Placebo	PF-04950615 150 mg	Placebo (Extension Period)	Bococizumab ADA positive (Extension Period)	Bococizumab ADA negative (Extension Period)
Total subjects affected by non serious adverse events
subjects affected / exposed	138 / 1065 (12.96%)	177 / 1063 (16.65%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
Vascular disorders
Hypertension
Additional description: For extension period, non SAEs were not collected, hence actual population exposed is "0". Current presentation is a resolution to database limitation.
alternative assessment type: Systematic
subjects affected / exposed	61 / 1065 (5.73%)	47 / 1063 (4.42%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences all number	66	52	0	0	0
General disorders and administration site conditions
Injection site reaction
Additional description: For extension period, non SAEs were not collected, hence actual population exposed is "0". Current presentation is a resolution to database limitation.
alternative assessment type: Systematic
subjects affected / exposed	23 / 1065 (2.16%)	97 / 1063 (9.13%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences all number	36	329	0	0	0
Infections and infestations
Upper respiratory tract infection
Additional description: For extension period, non SAEs were not collected, hence actual population exposed is "0". Current presentation is a resolution to database limitation.
alternative assessment type: Systematic
subjects affected / exposed	60 / 1065 (5.63%)	50 / 1063 (4.70%)	0 / 47 (0.00%)	0 / 19 (0.00%)	0 / 39 (0.00%)
occurrences all number	68	56	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

18 Jul 2014

1. Treatment duration was reduced from 80 to 52 weeks. 2. Follow-up period was reduced from 8 to 6 weeks. 3. Number of SC injection over 52 weeks were updated. 4. Subjects with lacunar infarct were excluded from the study participation and a hepatitis C serology at the end of treatment was included.

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

Clinical Trial Results: A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study To Assess The Efficacy, Long-Term Safety And Tolerability Of PF-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

Primary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

Secondary: Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period

Secondary: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52

Secondary: Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

Secondary: Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12

Secondary: Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12

Secondary: Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Secondary: Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Secondary: Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12

Secondary: Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12

Secondary: Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12

Secondary: Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12

Secondary: Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Secondary: Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12

Secondary: Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Secondary: Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

Secondary: Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

Secondary: Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

Secondary: Plasma Concentration of PF-04950615 at Week 12, 24 and 52

Secondary: Plasma Concentration of PF-04950615 at Week 12, 24 and 52

Secondary: Number of Subjects With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions

Secondary: Number of Subjects With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb):Treatment Period

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb):Treatment Period

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period

Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 follow-up visit,, 71, 84, 97 and 110: Extension Period

Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 follow-up visit,, 71, 84, 97 and 110: Extension Period

Secondary: Number of Subjects who Changed Concomitant Medications During Extension Period

Secondary: Number of Subjects who Changed Concomitant Medications During Extension Period

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study To Assess The Efficacy, Long-Term Safety And Tolerability Of PF-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events