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Clinical Trial Results:
A randomized, double-blind, dose-finding study to evaluate the change in weight after 24 weeks treatment with 8 doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo

Summary
EudraCT number	2016-002868-14
Trial protocol	SK CZ AT HU GB
Global end of trial date	02 Aug 2018

Results information
Results version number	v1(current)
This version publication date	22 Aug 2019
First version publication date	22 Aug 2019
Other versions

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

CLIK066B2201

ISRCTN number

US NCT number

NCT03100058

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharmaceuticals

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma, AG, +41 613241111, novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma, AG, +41 613241111, Novartis.email@novartis.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

02 Aug 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Aug 2018

Was the trial ended prematurely?

Main objective of the trial

To determine the dose-response signal and assess the dose-response relationship of 2 dose regimens of LIK066 (2.5 mg, 10 mg, 50 mg and 150 mg qd, 2.5 mg, 5 mg, 25 mg and 50 mg twice daily (bid)) as measured by the percent change from baseline (BL) in body weight relative to placebo after 24 weeks of treatment.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

06 May 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 39

Country: Number of subjects enrolled

Canada: 41

Country: Number of subjects enrolled

Czech Republic: 49

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

Hungary: 48

Country: Number of subjects enrolled

Slovakia: 27

Country: Number of subjects enrolled

United States: 239

Worldwide total number of subjects

460

EEA total number of subjects

180

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)

387

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Overall, 674 patients were screened. Of the 460 patients who were randomized to the study, the majority (85.7%) completed Epoch 3. Of the 394 patients who completed Epoch 3 and entered Epoch 4, the majority (93.1%) completed the Epoch 4 study period.

Screening details

Period 1 title

Epoch 3

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Carer, Subject

Are arms mutually exclusive

Yes

LIK066 2.5mg qd (Epoch 3)

Arm description

LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2.5mg qd/oral tablets/24 weeks

LIK066 10mg qd (Epoch 3)

Arm description

LIK066 10mg qd (once daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

10mg qd/oral tablets/24 weeks

LIK066 50mg qd (Epoch 3)

Arm description

LIK066 50mg qd (once daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

50mg qd/oral tablets/24 weeks

LIK066 150mg qd (Epoch 3)

Arm description

LIK066 150mg qd (once daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

150mg qd /oral tablets/24 weeks

LIK066 2.5mg bid (Epoch 3)

Arm description

LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2.5 mg bid/oral tablets/24 weeks

LIK066 5mg bid (Epoch 3)

Arm description

LIK066 5mg bid (twice daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

5mg bid/oral tablets/24 weeks

LIK066 25mg bid (Epoch 3)

Arm description

LIK066 25mg bid (twice daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

25mg bid/oral tablets/24 weeks

LIK066 50mg bid (Epoch 3)

Arm description

LIK066 50mg bid (twice daily) dosing frequency for 24 weeks

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

50mg bid/oral tablets/24 weeks

Placebo (Epoch 3)

Arm description

Matching placebo tablets for 24 weeks

Arm type

Placebo

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo/oral tablets/24 weeks

Number of subjects in period 1	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Started	38	38	38	77	38	39	38	76	78
Completed	35	31	29	63	36	37	30	60	73
Not completed	3	7	9	14	2	2	8	16	5
Adverse event, serious fatal	-	1	-	-	-	-	-	-	-
Consent withdrawn by subject	2	4	3	4	1	1	1	4	2
Physician decision	-	-	-	1	-	-	-	1	-
Adverse event, non-fatal	-	-	4	8	1	-	3	11	2
Pregnancy	1	-	-	-	-	-	-	-	-
Lost to follow-up	-	1	1	-	-	-	1	-	1
non-compliance with study treatment	-	1	1	-	-	1	1	-	-
Protocol deviation	-	-	-	1	-	-	1	-	-
Lack of efficacy	-	-	-	-	-	-	1	-	-

Period 2 title

Epoch 4

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

LIK066 qd/LIK066 25 mg qd (Epoch 4)

Arm description

LIK066 qd (once daily) patients who entered Epoch 4 and received LIK066 25 mg qd

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

LIK066 25 mg qd/oral tablets/24 weeks

LIK066 bid/LIK066 35 mg qd

Arm description

LIK066 bid patients who entered Epoch 4 and received LIK066 35 mg qd

Arm type

Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

LIK066 35 mg qd/oral tablets/24 weeks

Placebo/LIK066 25 mg qd

Arm description

Matching placebo tablets for 24 weeks

Arm type

Placebo/Experimental

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

LIK066 325 mg qd

Placebo qd (Epoch 4)

Arm description

Placebo patients who entered Epoch 4 and received matching Placebo tablets qd

Arm type

Placebo

Investigational medicinal product name

Licogliflozin

Investigational medicinal product code

LIK066

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo/oral tablets/24 weeks

Number of subjects in period 2	LIK066 qd/LIK066 25 mg qd (Epoch 4)	LIK066 bid/LIK066 35 mg qd	Placebo/LIK066 25 mg qd	Placebo qd (Epoch 4)
Started	158	163	39	34
Completed	153	148	36	30
Not completed	5	15	3	4
Adverse event, serious fatal	-	1	-	-
Consent withdrawn by subject	-	4	2	1
Adverse event, non-fatal	4	7	-	2
Pregnancy	-	-	-	1
Lost to follow-up	-	3	1	-
non-compliance with study treatment	1	-	-	-

Baseline characteristics

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Reporting group title

LIK066 2.5mg qd (Epoch 3)

Reporting group description

LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 10mg qd (Epoch 3)

Reporting group description

LIK066 10mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 50mg qd (Epoch 3)

Reporting group description

LIK066 50mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 150mg qd (Epoch 3)

Reporting group description

LIK066 150mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 2.5mg bid (Epoch 3)

Reporting group description

LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 5mg bid (Epoch 3)

Reporting group description

LIK066 5mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 25mg bid (Epoch 3)

Reporting group description

LIK066 25mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 50mg bid (Epoch 3)

Reporting group description

LIK066 50mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

Placebo (Epoch 3)

Reporting group description

Matching placebo tablets for 24 weeks

Reporting group values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)	Total
Number of subjects	38	38	38	77	38	39	38	76	78	460
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	32	34	29	64	30	35	35	62	66	387
From 65-84 years	6	4	9	13	8	4	3	14	12	73
85 years and over	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	51.3 ( 12.20 )	53.2 ( 10.08 )	52.9 ( 13.60 )	51.1 ( 12.94 )	53.4 ( 12.28 )	49.8 ( 11.50 )	49.7 ( 11.93 )	52.9 ( 11.87 )	51.1 ( 13.27 )	-
Sex: Female, Male
Units: Subjects
Female	23	27	25	44	20	24	26	49	45	283
Male	15	11	13	33	18	15	12	27	33	177
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	0	0	0	0	0	0	2	2	6
Asian	0	0	0	2	0	2	0	5	1	10
Native Hawaiian or Other Pacific Islander	0	0	0	2	0	0	0	0	1	3
Black or African American	5	4	5	5	2	3	4	6	8	42
White	30	33	33	67	36	32	34	63	64	392
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	1	1	0	1	0	2	0	0	2	7

Subject analysis set title

LIK066 qd/LIK066 25mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily

Subject analysis set title

LIK066 bid/LIK066 35mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo/LIK066 25mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo/Placebo (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis sets values	LIK066 qd/LIK066 25mg qd (Epoch 4)	LIK066 bid/LIK066 35mg qd (Epoch 4)	Placebo/LIK066 25mg qd (Epoch 4)	Placebo/Placebo (Epoch 4)
Number of subjects	158	163	39	34
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	132	138	35	26
From 65-84 years	26	24	4	8
85 years and over	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	( )	( )	( )	( )
Sex: Female, Male
Units: Subjects
Female	96	99	22	20
Male	62	63	17	14
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	2	0	2
Asian	13	14	2	3
Native Hawaiian or Other Pacific Islander	1	0	0	1
Black or African American	13	14	2	3
White	138	137	35	27
More than one race	0	0	0	0
Unknown or Not Reported	2	2	2	0

End points

Top of page

Reporting group title

LIK066 2.5mg qd (Epoch 3)

Reporting group description

LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 10mg qd (Epoch 3)

Reporting group description

LIK066 10mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 50mg qd (Epoch 3)

Reporting group description

LIK066 50mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 150mg qd (Epoch 3)

Reporting group description

LIK066 150mg qd (once daily) dosing frequency for 24 weeks

Reporting group title

LIK066 2.5mg bid (Epoch 3)

Reporting group description

LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 5mg bid (Epoch 3)

Reporting group description

LIK066 5mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 25mg bid (Epoch 3)

Reporting group description

LIK066 25mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

LIK066 50mg bid (Epoch 3)

Reporting group description

LIK066 50mg bid (twice daily) dosing frequency for 24 weeks

Reporting group title

Placebo (Epoch 3)

Reporting group description

Matching placebo tablets for 24 weeks

Reporting group title

LIK066 qd/LIK066 25 mg qd (Epoch 4)

Reporting group description

LIK066 qd (once daily) patients who entered Epoch 4 and received LIK066 25 mg qd

Reporting group title

LIK066 bid/LIK066 35 mg qd

Reporting group description

LIK066 bid patients who entered Epoch 4 and received LIK066 35 mg qd

Reporting group title

Placebo/LIK066 25 mg qd

Reporting group description

Matching placebo tablets for 24 weeks

Reporting group title

Placebo qd (Epoch 4)

Reporting group description

Placebo patients who entered Epoch 4 and received matching Placebo tablets qd

Subject analysis set title

LIK066 qd/LIK066 25mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

LIK066 bid/LIK066 35mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo/LIK066 25mg qd (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo/Placebo (Epoch 4)

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Percent change from baseline in body weight at 24 weeks

Top of page

End point title

Percent change from baseline in body weight at 24 weeks

End point description

Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment

End point type

Primary

End point timeframe

Baseline, Week 24 (Epoch 3)

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	38	76	78
Units: Percent change
number (confidence interval 95%)	-1.24 (-2.50 to -0.45)	-2.04 (-3.36 to -0.88)	-3.52 (-4.62 to -1.87)	-4.37 (-5.36 to -3.37)	-1.67 (-2.61 to -0.27)	-2.51 (-3.94 to -1.32)	-4.06 (-5.52 to -2.87)	-4.47 (-5.49 to -3.48)	-0.63 (-1.56 to 0.37)

LIK066 2.5 mg qd vs. Placebo

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-3.17

upper limit

-0.29

Notes
[1] - Dose finding study

LIK066 2.5mg qd vs Placebo

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[2]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-1.93

Confidence interval

level

95%

sides

2-sided

lower limit

-3.36

upper limit

-0.5

Notes
[2] - Dose finding study

LIK066 50mg qd vs Placebo

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.86

upper limit

-1.75

Notes
[3] - Dose finding study

LIK066 150mg qd vs Placebo

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[4]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.42

Confidence interval

level

95%

sides

2-sided

lower limit

-5.39

upper limit

-3.44

Notes
[4] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[5]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-2.53

upper limit

-0.25

Notes
[5] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[6]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.74

Confidence interval

level

95%

sides

2-sided

lower limit

-4.11

upper limit

-1.36

Notes
[6] - Dose finding study

LIK066 25mg bid vs Placebo

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[7]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.11

Confidence interval

level

95%

sides

2-sided

lower limit

-5.54

upper limit

-2.68

Notes
[7] - Dose finding study

LIK066 50mg bid vs Placebo

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[8]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.48

Confidence interval

level

95%

sides

2-sided

lower limit

-5.54

upper limit

-3.43

Notes
[8] - Dose finding study

Secondary: Number of subjects with response rate according to percent decrease in body weight for overall study

Top of page

End point title

Number of subjects with response rate according to percent decrease in body weight for overall study

End point description

Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	75	78
Units: Percentage
number (not applicable)
>=5%	26.3	15.8	34.2	42.9	15.8	20.5	37.8	45.3	12.8
>=10%	5.3	5.3	5.3	6.5	5.3	2.6	10.8	9.3	3.8

LIK066 2.5mg qd vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[9]

P-value

= 0.099

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

2.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

6.67

Notes
[9] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[10]

P-value

= 0.779

Method

ANCOVA

Parameter type

Log odds ratio

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

3.84

Notes
[10] - Dose finding study

LIk066 50mg qd vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[11]

P-value

= 0.011

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

3.69

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

10.11

Notes
[11] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[12]

P-value

< 0.001

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

5.57

Confidence interval

level

95%

sides

2-sided

lower limit

2.41

upper limit

12.88

Notes
[12] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[13]

P-value

= 0.812

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

3.74

Notes
[13] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[14]

P-value

= 0.229

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

5.69

Notes
[14] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

^[15]

P-value

= 0.004

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

4.29

Confidence interval

level

95%

sides

2-sided

lower limit

1.61

upper limit

11.46

Notes
[15] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

>=5%

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

^[16]

P-value

< 0.001

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

6.37

Confidence interval

level

95%

sides

2-sided

lower limit

2.72

upper limit

14.93

Notes
[16] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[17]

P-value

= 0.943

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

12.41

Notes
[17] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[18]

P-value

= 0.465

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

2.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

15.77

Notes
[18] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[19]

P-value

= 0.696

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

17.15

Notes
[19] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[20]

P-value

= 0.389

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

2.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

12.1

Notes
[20] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[21]

P-value

= 0.976

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

11.87

Notes
[21] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[22]

P-value

= 0.986

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

11.7

Notes
[22] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

^[23]

P-value

= 0.181

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

3.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

22.18

Notes
[23] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

>=10%

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

^[24]

P-value

= 0.1

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

3.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

20.54

Notes
[24] - Dose finding study

Secondary: Number of subjects with response rate according to percent decrease in body weight for Subgroups

Top of page

End point title

Number of subjects with response rate according to percent decrease in body weight for Subgroups

End point description

Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM)

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	75	78
Units: Percentage
number (not applicable)
Dysglycemic (>=5%)	31.3	25.0	40.0	48.4	6.7	37.5	40.0	41.9	9.7
Normoglycemic (>=5%)	44.4	11.1	44.4	47.4	11.1	11.1	55.6	52.9	20.0
Type 2 Diabetes Mellitus (T2DM) (>=5%)	7.7	15.4	28.6	37.0	28.6	14.3	30.8	44.4	14.8

LIK066 2.5mg qd vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[25]

P-value

= 0.048

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

6.29

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

38.76

Notes
[25] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

>=5% (Dsyglycemic)

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[26]

P-value

= 0.171

Method

ANCOVA

Parameter type

Log odds ratio

Point estimate

3.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

28.03

Notes
[26] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[27]

P-value

= 0.041

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

7.17

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

47.27

Notes
[27] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[28]

P-value

= 0.003

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

11.89

Confidence interval

level

95%

sides

2-sided

lower limit

2.32

upper limit

60.93

Notes
[28] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[29]

P-value

= 0.976

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.08

upper limit

11.72

Notes
[29] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[30]

P-value

= 0.022

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

8.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

56.44

Notes
[30] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

^[31]

P-value

= 0.032

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

7.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

46.99

Notes
[31] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

>=5% (Dysglycemic)

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

^[32]

P-value

= 0.005

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

11.28

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

60.46

Notes
[32] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[33]

P-value

= 0.227

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

3.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

21.28

Notes
[33] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[34]

P-value

= 0.763

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

7.85

Notes
[34] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[35]

P-value

= 0.095

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

4.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

28.7

Notes
[35] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[36]

P-value

= 0.033

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

5.33

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

24.83

Notes
[36] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[37]

P-value

= 0.788

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

8.1

Notes
[37] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[38]

P-value

= 0.751

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

7.62

Notes
[38] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

^[39]

P-value

= 0.027

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

8.05

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

51.09

Notes
[39] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

>=5% (Normoglycemic)

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

^[40]

P-value

= 0.023

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

6.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

Notes
[40] - Dose finding study

LIK066 2.5 mg qd vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[41]

P-value

= 0.528

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

4.78

Notes
[41] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[42]

P-value

= 0.958

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

6.68

Notes
[42] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[43]

P-value

= 0.546

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

9.49

Notes
[43] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[44]

P-value

= 0.098

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

3.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

11.75

Notes
[44] - Dose finding test

LIK066 2.5 mg bid vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[45]

P-value

= 0.563

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

8.7

Notes
[45] - Dose finding study

LIK066 5 mg bid vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[46]

P-value

= 0.61

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

5.38

Notes
[46] - Dose finding study

LIK066 25 mg bid vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

^[47]

P-value

= 0.528

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

9.16

Notes
[47] - Dose finding study

LIK066 50 mg bid vs Placebo

Statistical analysis description

>=5% (T2DM)

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

^[48]

P-value

= 0.023

Method

ANCOVA

Parameter type

Odds ratio (OR)

Point estimate

4.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

16.9

Notes
[48] - Dose finding study

Secondary: Change from baseline on waist circumference

Top of page

End point title

Change from baseline on waist circumference

End point description

Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest.

End point type

Secondary

End point timeframe

Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: Percentage Change

arithmetic mean (confidence interval 95%)

-2.1 (-3.87 to -0.31)

-2.7 (-4.55 to -0.92)

-3.7 (-5.55 to -1.82)

-5.6 (-6.84 to -4.35)

-2.7 (-4.47 to -0.91)

-4.3 (-6.07 to -2.57)

-4.8 (-6.61 to -2.98)

-4.6 (-5.89 to -3.31)

-1.3 (-2.54 to -0.05)

-0.4 (-1.25 to 0.36)

-0.7 (-1.53 to 0.10)

-2.1 (-3.73 to -0.38)

0.4 (-1.37 to 2.20)

LIK066 2.5 mg qd vs Placebo

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[49]

P-value

= 0.47

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.96

upper limit

1.37

Notes
[49] - Dose finding study

LIK066 10mg qd vs Placebo

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[50]

P-value

= 0.199

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.64

upper limit

0.76

Notes
[50] - Dose finding study

LIK066 150mg qd vs Placebo

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[51]

P-value

< 0.001

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.64

upper limit

0.76

Notes
[51] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[52]

P-value

= 0.206

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.56

upper limit

0.77

Notes
[52] - Dose finding study

LIK066 5mg bid vs Placebo

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[53]

P-value

= 0.006

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.18

upper limit

-0.88

Notes
[53] - Dose finding study

LIK066 50mg bid vs Placebo

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[54]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

-1.51

Notes
[54] - Dose finding study

LIK066 25mg bid vs Placebo

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[55]

P-value

= 0.002

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

-1.3

Notes
[55] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[56]

P-value

= 0.259

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

0.84

Notes
[56] - Dose finding study

LIK066 qd/LIK066 25 mg qd vs Placebo

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[57]

P-value

= 0.391

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.82

upper limit

1.1

Notes
[57] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[58]

P-value

= 0.048

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.91

upper limit

-0.02

Notes
[58] - Dose finding study

Secondary: Change from baseline in fasting plasma glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)

Top of page

End point title

Change from baseline in fasting plasma glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)

End point description

FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake).

End point type

Secondary

End point timeframe

Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: mmol/L

arithmetic mean (confidence interval 95%)

1.9 (0.55 to 3.19)

-0.1 (-1.46 to 1.27)

-1.2 (-2.60 to 0.26)

-0.8 (-1.70 to 0.16)

-0.5 (-1.80 to 0.86)

-1.1 (-2.37 to 0.27)

-0.9 (-2.28 to 0.46)

-1.0 (-1.96 to -0.13)

0.9 (-0.06 to 1.81)

-0.1 (-0.64 to 0.35)

-0.3 (-0.79 to 0.22)

-0.1 (-1.14 to 0.84)

0.6 (-0.54 to 1.73)

LIK066 2.5mg qd va Placebo

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[59]

P-value

= 0.225

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

2.61

Notes
[59] - Dose finding study

LIK066 10mg qd vs Placebo

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[60]

P-value

= 0.247

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.62

upper limit

0.68

Notes
[60] - Dose finding study

LIK066 50mg qd vs Placebo

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[61]

P-value

= 0.019

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.75

upper limit

-0.34

Notes
[61] - Dose finding study

LIK066 150mg qd vs Placebo

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[62]

P-value

= 0.015

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.96

upper limit

-0.33

Notes
[62] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[63]

P-value

= 0.106

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.97

upper limit

0.29

Notes
[63] - Dose finding study

LIK066 5mg bid vs Placebo

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[64]

P-value

= 0.02

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.54

upper limit

-0.31

Notes
[64] - Dose finding study

LIK066 25mg bid vs Placebo

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[65]

P-value

= 0.035

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

-0.12

Notes
[65] - Dose finding study

LIK066 50mg bid vs Placebo

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[66]

P-value

= 0.004

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.22

upper limit

-0.61

Notes
[66] - Dose finding study

Secondary: Change from baseline in glycated hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus patients (T2DM)

Top of page

End point title

Change from baseline in glycated hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus patients (T2DM)

End point description

HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory.

End point type

Secondary

End point timeframe

Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: Percentage change

arithmetic mean (confidence interval 95%)

0.1 (-0.23 to 0.45)

-0.5 (-0.82 to -0.13)

-0.9 (-1.24 to -0.50)

-0.7 (-0.92 to -0.44)

-0.3 (-0.68 to 0.00)

-0.5 (-0.83 to -0.15)

-0.6 (-0.98 to -0.28)

-0.6 (-0.87 to -0.40)

-0.3 (-0.50 to -0.02)

0.2 (0.03 to 0.38)

0.0 (-0.13 to 0.22)

-0.1 (-0.49 to 0.24)

0.3 (-0.07 to 0.71)

LIK066 2.5mg qd vs Placebo

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[67]

P-value

= 0.082

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.79

Notes
[67] - Dose finding study

LIK066 10mg qd vs Placebo

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[68]

P-value

= 0.319

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.63

upper limit

0.21

Notes
[68] - Dose finding study

LIK066 50mg qd vs Placebo

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[69]

P-value

= 0.008

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.16

Notes
[69] - Dose finding study

LIK066 150mg qd vs Placebo

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[70]

P-value

= 0.015

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

-0.08

Notes
[70] - Dose finding study

LIK066 5mg bid vs Placebo

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[71]

P-value

= 0.28

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

0.19

Notes
[71] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[72]

P-value

= 0.707

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.34

Notes
[72] - Dose finding study

LIK066 25mg bid vs Placebo

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[73]

P-value

= 0.086

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.05

Notes
[73] - Dose finding study

LIK066 50mg bid vs Placebo

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[74]

P-value

= 0.03

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

-0.04

Notes
[74] - Dose finding study

Secondary: Change from baseline in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP)

Top of page

End point title

Change from baseline in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP)

End point description

At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured

End point type

Secondary

End point timeframe

Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: mmHg

arithmetic mean (confidence interval 95%)

systolic blood pressure (SBP)

-1.2 (-4.38 to 1.93)

-1.5 (-4.38 to 1.93)

-4.9 (-8.30 to -1.52)

-1.2 (-3.38 to 1.06)

-0.7 (-3.86 to 2.43)

0.8 (-2.38 to 3.88)

-2.6 (-5.82 to 0.69)

-1.8 (-4.15 to 0.48)

1.6 (-0.67 to 3.80)

-0.9 (-2.66 to 0.79)

-1.6 (-3.39 to 0.10)

-5.6 (-9.22 to -2.06)

0.8 (-2.97 to 4.65)

diastolic blood pressure (DBP)

-0.2 (-2.37 to 2.00)

0.1 (-2.21 to 2.40)

-2.3 (-4.62 to 0.07)

-1.3 (-2.82 to 0.26)

0.8 (-1.35 to 3.02)

-1.4 (-3.57 to 0.78)

0.3 (-1.99 to 2.54)

-1.7 (-3.26 to -0.06)

0.5 (-1.03 to 2.08)

-0.6 (-1.69 to 0.56)

-1.2 (-2.30 to -0.04)

-2.0 (-4.33 to 0.34)

0.6 (-1.89 to 3.06)

LIK066 2.5mg qd vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[75]

P-value

= 0.156

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.64

upper limit

1.07

Notes
[75] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[76]

P-value

= 0.127

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.11

upper limit

0.89

Notes
[76] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[77]

P-value

= 0.002

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.52

upper limit

-2.42

Notes
[77] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[78]

P-value

= 0.089

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.86

upper limit

0.42

Notes
[78] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[79]

P-value

= 0.245

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.12

upper limit

1.57

Notes
[79] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[80]

P-value

= 0.678

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.65

upper limit

3.02

Notes
[80] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[81]

P-value

= 0.04

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8.07

upper limit

-0.19

Notes
[81] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

SBP

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[82]

P-value

= 0.038

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.61

upper limit

-0.19

Notes
[82] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[83]

P-value

= 0.601

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.38

upper limit

1.96

Notes
[83] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[84]

P-value

= 0.76

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

2.34

Notes
[84] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[85]

P-value

= 0.051

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

0.01

Notes
[85] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[86]

P-value

= 0.105

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.98

upper limit

0.38

Notes
[86] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[87]

P-value

= 0.82

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.36

upper limit

2.98

Notes
[87] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[88]

P-value

= 0.157

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.58

upper limit

0.74

Notes
[88] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[89]

P-value

= 0.859

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.99

upper limit

2.49

Notes
[89] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

DBP

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[90]

P-value

= 0.054

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.41

upper limit

0.04

Notes
[90] - Dose finding study

Secondary: Change from baseline in 24-hour urinary glucose excretion

Top of page

End point title

Change from baseline in 24-hour urinary glucose excretion

End point description

Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory.

End point type

Secondary

End point timeframe

Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: mmol/24hr

arithmetic mean (confidence interval 95%)

208.6 (101.85 to 315.40)

134.6 (-8.69 to 277.85)

377.0 (206.19 to 547.90)

306.1 (199.59 to 412.62)

183.0 (32.37 to 333.70)

193.8 (82.22 to 305.31)

241.3 (135.13 to 347.30)

308.9 (198.27 to 419.53)

-17.8 (-94.20 to 58.61)

26.8 (-30.03 to 83.70)

122.5 (69.82 to 175.26)

248.0 (137.72 to 358.33)

-148.9 (-269.62 to -28.10)

No statistical analyses for this end point

Secondary: Change in Weight in the overall population and by subgroups (Epoch 4)

Top of page

End point title

Change in Weight in the overall population and by subgroups (Epoch 4)

End point description

Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4)

End point type

Secondary

End point timeframe

Between Week 24 and Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: kg

arithmetic mean (confidence interval 95%)

0 (0 to 0)

-0.2 (-0.70 to 0.33)

-0.2 (-0.68 to 0.35)

-2.4 (-3.47 to -1.33)

0.4 (-0.74 to 1.55)

LIK066 qd/LIK066 25mg qd vs Placebo

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[91]

P-value

= 0.355

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

0.66

Notes
[91] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[92]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.36

upper limit

-1.24

Notes
[92] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[93]

P-value

= 0.373

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.83

upper limit

0.69

Notes
[93] - Dose finding study

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary calcium excretion

Top of page

End point title

Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary calcium excretion

End point description

Evaluation of 24-hour urinary calcium excretion after 24 week of treatment.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	38	76	78
Units: mmol/24hr
arithmetic mean (standard deviation)
Baseline	49.6 ( 25.08 )	33.1 ( 29.65 )	40.2 ( 21.55 )	34.6 ( 17.56 )	44.7 ( 26.83 )	43.6 ( 16.91 )	38.0 ( 22.13 )	47.9 ( 23.64 )	43.0 ( 22.63 )
Week 24 (Timepoint 1)	48.8 ( 26.59 )	38.1 ( 32.20 )	39.8 ( 22.48 )	40.1 ( 18.20 )	52.4 ( 32.78 )	45.9 ( 15.41 )	38.0 ( 22.13 )	48.1 ( 21.93 )	44.7 ( 23.0 )
Week 24 (Timepoint 2)	54.2 ( 29.34 )	42.0 ( 29.99 )	39.2 ( 20.24 )	62.8 ( 34.26 )	51.2 ( 35.32 )	54.6 ( 23.77 )	37.9 ( 32.33 )	53.0 ( 26.95 )	52.2 ( 30.75 )
Week 24 (Timepoint 3)	5.4 ( 22.74 )	3.9 ( 19.56 )	-0.6 ( 12.07 )	22.8 ( 28.42 )	-1.2 ( 7.77 )	8.7 ( 18.21 )	-0.1 ( 14.39 )	4.9 ( 26.20 )	7.5 ( 32.91 )

No statistical analyses for this end point

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary calcium excretion

Top of page

End point title

Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary calcium excretion

End point description

Evaluation of 24-hour urinary calcium after 48 weeks of treatment

End point type

Secondary

End point timeframe

Baseline, Week 24, Week 48

End point values	LIK066 qd/LIK066 25mg qd (Epoch 4)	LIK066 bid/LIK066 35mg qd (Epoch 4)	Placebo/LIK066 25mg qd (Epoch 4)	Placebo/Placebo (Epoch 4)
Number of subjects analysed	158	163	39	34
Units: mmol/24hr
arithmetic mean (standard deviation)
Baseline	4.8 ( 3.02 )	5.0 ( 2.84 )	4.6 ( 0.91 )	5.6 ( 4.07 )
Week 48(Timepoint 1)	5.1 ( 307 )	5.2 ( 2.95 )	4.5 ( 0.95 )	6.6 ( 4.55 )
Week 48(Timepoint 2)	4.6 ( 2.33 )	5.6 ( 4.55 )	5.4 ( 3.65 )	4.8 ( 2.10 )
Week 48(Timepoint 3)	-0.5 ( 3.41 )	0.4 ( 2.81 )	0.9 ( 4.10 )	-1.8 ( 3.26 )

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary phosphorus excretion

Top of page

End point title

Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary phosphorus excretion

End point description

Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment

End point type

Secondary

End point timeframe

Week 24, Week 48

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)	Placebo (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	38	76	78
Units: mmol/24hr
arithmetic mean (standard deviation)
Baseline	282.1 ( 128.10 )	240.5 ( 74.64 )	254.5 ( 105.70 )	291.5 ( 175.10 )	284.0 ( 117.60 )	241.8 ( 82.75 )	277.0 ( 99.67 )	293.7 ( 120.70 )	297.0 ( 145.10 )
Week 24 (Timepoint 1)	284.0 ( 140.10 )	239.7 ( 80.40 )	260.9 ( 111.10 )	275.0 ( 101.30 )	319.9 ( 32.78 )	246.5 ( 84.19 )	299.3 ( 79.06 )	302.5 ( 121.30 )	307.9 ( 145.90 )
Week 24 (Timepoint 2)	297.7 ( 117.40 )	295.3 ( 95.60 )	299.2 ( 145.50 )	264.7 ( 74.84 )	317.8 ( 205.10 )	341.6 ( 109.20 )	260.5 ( 124.80 )	289.3 ( 83.62 )	352.8 ( 159.30 )
Week 24 (Timepoint 3)	13.0 ( 132.00 )	55.6 ( 89.81 )	38.3 ( 70.00 )	-10.2 ( 103.60 )	-2.1 ( 159.60 )	95.1 ( 67.36 )	-38.7 ( 107.80 )	-13.2 ( 153.80 )	44.9 ( 177.60 )

No statistical analyses for this end point

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary phosphorus excretion

Top of page

End point title

Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary phosphorus excretion

End point description

Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment

End point type

Secondary

End point timeframe

Week 24, Week 48

End point values	LIK066 qd/LIK066 25mg qd (Epoch 4)	LIK066 bid/LIK066 35mg qd (Epoch 4)	Placebo/LIK066 25mg qd (Epoch 4)	Placebo/Placebo (Epoch 4)
Number of subjects analysed	158	163	39	34
Units: mmol/24hr
arithmetic mean (standard deviation)
Baseline	27.6 ( 11.46 )	30.5 ( 11.63 )	28.6 ( 14.11 )	40.2 ( 15.96 )
Week 48 (Timepoint 1)	27.5 ( 11.73 )	30.2 ( 11.85 )	28.6 ( 14.11 )	44.4 ( 17.60 )
Week 48 (Timepoint 2)	24.7 ( 12.74 )	31.1 ( 16.21 )	31.0 ( 14.67 )	29.0 ( 15.42 )
Week 48(Timepoint 3)	-2.8 ( 11.44 )	0.9 ( 14.52 )	2.4 ( 17.33 )	-15.5 ( 18.92 )

No statistical analyses for this end point

Secondary: Change from baseline in fasting lipid profile (lipoproteins)

Top of page

End point title

Change from baseline in fasting lipid profile (lipoproteins)

End point description

Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

End point type

Secondary

End point timeframe

Baseline, Week 24, Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: g/L

arithmetic mean (confidence interval 95%)

Apoliprotein A1

8.9 (4.26 to 13.61)

8.13 (3.27 to 13.30)

10.7 (5.38 to 15.97)

8.9 (5.55 to 12.21)

5.3 (0.487 to 10.17)

8.1 (3.44 to 12.86)

6.7 (1.75 to 11.59)

11.0 (7.47 to 14.44)

6.7 (3.41 to 10.06)

3.0 (0.92 to 5.10)

3.4 (1.22 to 5.51)

5.6 (1.35 to 9.89)

-0.7 (-5.27 to 3.87)

Apoliprotein B

2.9 (-5.32 to 11.08)

7.7 (-1.23 to 16.61)

3.3 (-6.06 to 12.72)

12.4 (6.57 to 18.32)

-0.4 (-8.91 to 8.18)

4.5 (-3.84 to 12.74)

2.3 (-6.36 to 10.98)

3.9 (-2.29 to 10.01)

5.8 (-0.03 to 11.69)

-1.7 (-4.39 to 1.08)

-2.4 (-5.23 to 0.38)

-2.3 (-7.85 to 3.31)

-2.0 (-8.00 to 3.96)

No statistical analyses for this end point

Secondary: Change from baseline in High sensitive C-reactive protein (hsCRP)

Top of page

End point title

Change from baseline in High sensitive C-reactive protein (hsCRP)

End point description

Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

End point type

Secondary

End point timeframe

Baseline to Week 24, Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: mg/L

geometric mean (confidence interval 95%)

0.99 (0.78 to 1.25)

1.06 (0.83 to 1.36)

1.31 (1.01 to 1.69)

0.98 (0.83 to 1.16)

1.02 (0.80 to 1.30)

0.93 (0.74 to 118)

1.00 (0.78 to 1.27)

0.98 (0.83 to 1.17)

0.92 (0.78 to 1.09)

0.95 (0.85 to 1.06)

0.93 (0.83 to 1.04)

0.96 (0.77 to 1.20)

1.07 (0.84 to 1.36)

LIK066 2.5mg qd vs Placebo

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[94]

P-value

= 0.632

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.42

Notes
[94] - Dose finding study

LIK066 10mg qd vs Placebo

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[95]

P-value

= 0.352

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.55

Notes
[95] - Dose finding study

LIK066 50mg qd vs Placeob

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[96]

P-value

= 0.027

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.92

Notes
[96] - Dose finding study

LIK066 150mg qd vs Placebo

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[97]

P-value

= 0.587

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.35

Notes
[97] - Dose finding study

LIK066 2.5mg bid vs Placebo

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[98]

P-value

= 0.508

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.47

Notes
[98] - Dose finding study

LIK066 5mg bid vs Placebo

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[99]

P-value

= 0.945

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.34

Notes
[99] - Dose finding study

LIK066 25mg bid vs Placebo

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[100]

P-value

= 0.602

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.45

Notes
[100] - Dose finding study

LIK066 50mg bid vs Placebo

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[101]

P-value

= 0.612

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.35

Notes
[101] - Dose finding study

LIK066 qd/LIK066 25mg qd vs Placebo

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[102]

P-value

= 0.382

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.16

Notes
[102] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[103]

P-value

= 0.31

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.14

Notes
[103] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[104]

P-value

= 0.525

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.25

Notes
[104] - Dose finding study

Secondary: Change from baseline in fasting lipid profile (triglycerides/cholesterol)

Top of page

End point title

Change from baseline in fasting lipid profile (triglycerides/cholesterol)

End point description

Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

End point type

Secondary

End point timeframe

Baseline to Week 24, Week 24 to Week 48 (Epoch 4)

LIK066 2.5mg qd (Epoch 3)

LIK066 10mg qd (Epoch 3)

LIK066 50mg qd (Epoch 3)

LIK066 150mg qd (Epoch 3)

LIK066 2.5mg bid (Epoch 3)

LIK066 5mg bid (Epoch 3)

LIK066 25mg bid (Epoch 3)

LIK066 50mg bid (Epoch 3)

Placebo (Epoch 3)

LIK066 qd/LIK066 25mg qd (Epoch 4)

LIK066 bid/LIK066 35mg qd (Epoch 4)

Placebo/LIK066 25mg qd (Epoch 4)

Placebo/Placebo (Epoch 4)

Number of subjects analysed

158

163

Units: mmol/L

arithmetic mean (confidence interval 95%)

Triglycerides (TG)

-3.8 (-14.91 to 7.26)

1.3 (-11.19 to 13.80)

-11.5 (-24.03 to .093)

-3.0 (-10.94 to 4.91)

2.3 (-8.94 to 13.57)

1.7 (-9.30 to 12.77)

5.5 (-5.94 to 16.89)

-7.4 (-15.60 to 0.87)

4.0 (-3.82 to 11.87)

6.7 (0.18 to 13.13)

12.4 (5.75 to 19.13)

-0.9 (-14.48 to 12.59)

4.8 (-9.57 to 19.16)

Total Cholesterol (TC)

6.0 (-0.92 to 12.99)

7.3 (-0.23 to 14.92)

4.8 (-3.15 to 12.78)

14.6 (9.61 to 19.58)

1.5 (-5.79 to 8.71)

5.1 (-1.89 to 12.19)

6.4 (-0.94 to 13.75)

8.8 (-0.23 to 9.70)

4.7 (-0.23 to 9.70)

0.8 (-1.65 to 3.27)

0.3 (-2.22 to 2.81)

0.8 (-4.22 to 5.81)

-1.7 (-7.04 to 3.68)

HDL Cholesterol

0.8 (-5.25 to 6.76)

4.9 (-1.52 to 11.28)

5.2 (-1.55 to 12.01)

8.0 (3.71 to 12.25)

2.9 (-3.29 to 9.16)

2.4 (-3.60 to 8.48)

1.5 (-4.86 to 7.81)

8.0 (3.56 to 12.47)

0.7 (-3.54 to 5.00)

3.9 (0.84 to 7.03)

3.7 (0.54 to 6.90)

9.2 (2.88 to 15.57)

0.7 (-6.11 to 7.48)

LDL Cholesterol

8.7 (-2.14 to 19.61)

17.5 (5.73 to 29.20)

8.2 (-4.21 to 20.25)

21.8 (14.08 to 29.55)

4.1 (-7.22 to 15.38)

8.7 (-2.26 to 19.68)

7.7 (-3.77 to 19.13)

10.9 (2.80 to 19.04)

12.5 (4.70 to 20.30)

-0.6 (-4.14 to 2.96)

-1.2 (-4.79 to 2.49)

-1.4 (-8.66 to 5.83)

-3.5 (-11.28 to 4.24)

LIK066 2.5mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[105]

P-value

= 0.254

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-21.37

upper limit

5.65

Notes
[105] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[106]

P-value

= 0.716

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-17.44

upper limit

11.99

Notes
[106] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[107]

P-value

= 0.038

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-15.6

Confidence interval

level

95%

sides

2-sided

lower limit

-30.3

upper limit

-0.86

Notes
[107] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[108]

P-value

= 0.213

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-18.15

upper limit

4.06

Notes
[108] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[109]

P-value

= 0.806

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-15.38

upper limit

11.96

Notes
[109] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[110]

P-value

= 0.739

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.8

upper limit

11.21

Notes
[110] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

P-value

= 0.049

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-11.4

Confidence interval

level

95%

sides

2-sided

lower limit

-22.71

upper limit

-0.07

LIK066 25mg bid vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[111]

P-value

= 0.837

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-12.36

upper limit

15.26

Notes
[111] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[112]

P-value

= 0.764

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.22

upper limit

9.82

Notes
[112] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[113]

P-value

= 0.571

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.43

upper limit

11.63

Notes
[113] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[114]

P-value

= 0.987

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

9.46

Notes
[114] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[115]

P-value

= 0.006

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

9.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.85

upper limit

16.87

Notes
[115] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[116]

P-value

= 0.463

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-12.03

upper limit

5.48

Notes
[116] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[117]

P-value

= 0.925

Method

ANOVA

Parameter type

Mean difference (net)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.18

upper limit

9.01

Notes
[117] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[118]

P-value

= 0.711

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.19

upper limit

10.53

Notes
[118] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[119]

P-value

= 0.265

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

11.26

Notes
[119] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[120]

P-value

= 0.995

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.31

upper limit

7.36

Notes
[120] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[121]

P-value

= 0.288

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.52

upper limit

11.81

Notes
[121] - Dose finding study

LIK066 50mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[122]

P-value

= 0.269

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

12.5

Notes
[122] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

^[123]

P-value

= 0.018

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

13.27

Notes
[123] - Dose finding study

LIK066 2.5mg bid vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[124]

P-value

= 0.565

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.32

upper limit

9.73

Notes
[124] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[125]

P-value

= 0.649

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.67

upper limit

9.09

Notes
[125] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[126]

P-value

= 0.847

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.87

upper limit

8.36

Notes
[126] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[127]

P-value

= 0.02

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

13.43

Notes
[127] - Dose finding study

LIK066 2.5mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 2.5mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[128]

P-value

= 0.579

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-17.09

upper limit

9.57

Notes
[128] - Dose finding study

LIK066 10mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 10mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

P-value

= 0.487

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-9.08

upper limit

19.02

LIK066 50mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 50mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[129]

P-value

= 0.561

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-18.96

upper limit

10.3

Notes
[129] - Dose finding study

LIK066 150mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 150mg qd (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

P-value

= 0.097

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

9.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

20.25

LIK066 2.5mg bid vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 2.5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[130]

P-value

= 0.227

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-8.4

Confidence interval

level

95%

sides

2-sided

lower limit

-22.1

upper limit

5.26

Notes
[130] - Dose finding study

LIK066 5mg bid vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 5mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

^[131]

P-value

= 0.58

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-17.22

upper limit

9.64

Notes
[131] - Dose finding study

LIK066 25mg bid vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 25mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

^[132]

P-value

= 0.494

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-18.67

upper limit

9.03

Notes
[132] - Dose finding study

LIK066 50mg bid vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 50mg bid (Epoch 3) v Placebo (Epoch 3)

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

^[133]

P-value

= 0.782

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-12.81

upper limit

9.65

Notes
[133] - Dose finding study

LIK066 qd/LIK066 25mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[134]

P-value

= 0.816

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13.82

upper limit

17.54

Notes
[134] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[135]

P-value

= 0.341

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

8.02

Confidence interval

level

95%

sides

2-sided

lower limit

-8.13

upper limit

23.42

Notes
[135] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Statistical analysis description

Triglycerides (TG)

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[136]

P-value

= 0.566

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

9.99

Confidence interval

level

95%

sides

2-sided

lower limit

-25.39

upper limit

13.91

Notes
[136] - Dose finding study

LIK066 qd/LIK066 25mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[137]

P-value

= 0.405

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-3.38

upper limit

8.36

Notes
[137] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[138]

P-value

= 0.511

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.92

upper limit

7.87

Notes
[138] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Statistical analysis description

Total Cholesterol (TC)

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[139]

P-value

= 0.506

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.83

upper limit

9.79

Notes
[139] - Dose finding study

LIK066 qd/LIK066 25mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[140]

P-value

= 0.392

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

10.7

Notes
[140] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[141]

P-value

= 0.426

Method

ANOVA

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.45

upper limit

10.53

Notes
[141] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Statistical analysis description

HDL Cholesterol

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[142]

P-value

= 0.071

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

17.8

Notes
[142] - Dose finding study

LIK066 qd/LIK066 25mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 qd/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

^[143]

P-value

= 0.498

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.56

upper limit

11.42

Notes
[143] - Dose finding study

LIK066 bid/LIK066 35mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

LIK066 bid/LIK066 35mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

^[144]

P-value

= 0.586

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.17

upper limit

10.9

Notes
[144] - Dose finding study

Placebo/LIK066 25mg qd vs Placebo

Statistical analysis description

LDL Cholesterol

Comparison groups

Placebo/LIK066 25mg qd (Epoch 4) v Placebo/Placebo (Epoch 4)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[145]

P-value

= 0.696

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8.47

upper limit

12.67

Notes
[145] - Dose finding study

Secondary: Pharmacokinetics of LIK066: Observe maximum plasma concentration (cmax)

Top of page

End point title

Pharmacokinetics of LIK066: Observe maximum plasma concentration (cmax) ^[146]

End point description

Observe maximum plasma concentration following administration of LIK066 (Cmax)

End point type

Secondary

End point timeframe

Summary at Week 24 from qd or bid regimens

Notes
[146] - 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: No statistical analysis done on PK parameters

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	76
Units: ng/mL
arithmetic mean (standard deviation)	80.0 ( 97.2 )	128 ( 00.0 )	798 ( 397 )	1810 ( 545 )	38.6 ( 5.22 )	84.2 ( 19.0 )	523 ( 118 )	811 ( 367 )

No statistical analyses for this end point

Secondary: Pharmacokinetics of LIK066: Time to reach the maximum concentration (Tmax)

Top of page

End point title

Pharmacokinetics of LIK066: Time to reach the maximum concentration (Tmax) ^[147]

End point description

Time to reach the maximum concentration after administration of LIK066 (Tmax)

End point type

Secondary

End point timeframe

Summary at Week 24 for qd or bid regimens

Notes
[147] - 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: No statistical analysis done on PK parameters

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	76
Units: hour
median (full range (min-max))	1.00 (1.00 to 2.00)	1.00 (1.00 to 1.00)	1.01 (1.00 to 2.08)	1.02 (1.00 to 2.00)	1.00 (0.983 to 1.00)	1.00 (0.917 to 2.00)	0.992 (0.900 to 1.00)	1.00 (0.983 to 2.00)

No statistical analyses for this end point

Secondary: Pharmacokinetics of LIK066: Area under the plasma concentration-time curve from time zero time 't' (AUC0-t)

Top of page

End point title

Pharmacokinetics of LIK066: Area under the plasma concentration-time curve from time zero time 't' (AUC0-t) ^[148]

End point description

Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t)

End point type

Secondary

End point timeframe

Summary at Week 24 from qd or bid regimens (0-6h)

Notes
[148] - 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: No statistical analysis done on PK parameters

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	76
Units: hr*ng/mL
arithmetic mean (standard deviation)	196 ( 186 )	275 ( 000 )	2280 ( 522 )	5700 ( 1490 )	105 ( 17.1 )	273 ( 69.3 )	1520 ( 277 )	2190 ( 841 )

No statistical analyses for this end point

Secondary: Pharmacokinetics of LIK066: Last non-zero concentration area under the curve (AUClast)

Top of page

End point title

Pharmacokinetics of LIK066: Last non-zero concentration area under the curve (AUClast) ^[149]

End point description

Last non-zero concentration area under the curve (AUClast)

End point type

Secondary

End point timeframe

Summary at Week 24 from qd or bid regimens

Notes
[149] - 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: No statistical analysis done on PK parameters

End point values	LIK066 2.5mg qd (Epoch 3)	LIK066 10mg qd (Epoch 3)	LIK066 50mg qd (Epoch 3)	LIK066 150mg qd (Epoch 3)	LIK066 2.5mg bid (Epoch 3)	LIK066 5mg bid (Epoch 3)	LIK066 25mg bid (Epoch 3)	LIK066 50mg bid (Epoch 3)
Number of subjects analysed	38	38	38	77	38	39	37	76
Units: hr*ng/mL
arithmetic mean (standard deviation)	196 ( 186 )	275 ( 000 )	2290 ( 526 )	5690 ( 1480 )	105 ( 17.2 )	273 ( 70.2 )	1520 ( 271 )	2190 ( 843 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Timeframe for AE

Adverse event reporting additional description

AE additional description

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

LIK066 2.5 mg qd/25 mg qd

Reporting group description

LIK066 2.5 mg qd/25 mg qd

Reporting group title

LIK066 10 mg qd/25 mg qd

Reporting group description

LIK066 10 mg qd/25 mg qd

Reporting group title

LIK066 50 mg qd/25 mg qd

Reporting group description

LIK066 50 mg qd/25 mg qd

Reporting group title

LIK066 150 mg qd/25 mg qd

Reporting group description

LIK066 150 mg qd/25 mg qd

Reporting group title

LIK066 2.5 mg bid/35 mg qd

Reporting group description

LIK066 2.5 mg bid/35 mg qd

Reporting group title

LIK066 5 mg bid/35 mg qd

Reporting group description

LIK066 5 mg bid/35 mg qd

Reporting group title

LIK066 25 mg bid/35 mg qd

Reporting group description

LIK066 25 mg bid/35 mg qd

Reporting group title

LIK066 50 mg bid/35 mg qd

Reporting group description

LIK066 50 mg bid/35 mg qd

Reporting group title

Placebo/LIK066 25 mg qd

Reporting group description

Placebo/LIK066 25 mg qd

Reporting group title

Placebo/Placebo

Reporting group description

Placebo/Placebo

Serious adverse events	LIK066 2.5 mg qd/25 mg qd	LIK066 10 mg qd/25 mg qd	LIK066 50 mg qd/25 mg qd	LIK066 150 mg qd/25 mg qd	LIK066 2.5 mg bid/35 mg qd	LIK066 5 mg bid/35 mg qd	LIK066 25 mg bid/35 mg qd	LIK066 50 mg bid/35 mg qd	Placebo/LIK066 25 mg qd	Placebo/Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 38 (7.89%)	3 / 38 (7.89%)	1 / 38 (2.63%)	3 / 77 (3.90%)	5 / 38 (13.16%)	2 / 39 (5.13%)	2 / 38 (5.26%)	1 / 76 (1.32%)	1 / 40 (2.50%)	4 / 38 (10.53%)
number of deaths (all causes)	0	1	0	0	1	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leiomyosarcoma
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain lower
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast enlargement
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysmenorrhoea
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspareunia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial hyperplasia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Diverticulitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	LIK066 2.5 mg qd/25 mg qd	LIK066 10 mg qd/25 mg qd	LIK066 50 mg qd/25 mg qd	LIK066 150 mg qd/25 mg qd	LIK066 2.5 mg bid/35 mg qd	LIK066 5 mg bid/35 mg qd	LIK066 25 mg bid/35 mg qd	LIK066 50 mg bid/35 mg qd	Placebo/LIK066 25 mg qd	Placebo/Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	33 / 38 (86.84%)	24 / 38 (63.16%)	24 / 38 (63.16%)	55 / 77 (71.43%)	31 / 38 (81.58%)	32 / 39 (82.05%)	26 / 38 (68.42%)	47 / 76 (61.84%)	32 / 40 (80.00%)	32 / 38 (84.21%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Benign neoplasm of conjunctiva
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Neuroma
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Papilloma
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	0	0
Hypertension
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	3 / 38 (7.89%)
occurrences all number	1	1	0	0	1	1	0	0	0	3
Hypotension
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	1	2	0	0	0	0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Peripheral venous disease
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Shock haemorrhagic
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Thrombophlebitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Chest discomfort
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Chest pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Chills
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Fatigue
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	0	1	0	1	0	0	1	0	1	2
Feeling cold
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Hunger
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Oedema peripheral
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	1	1	0	0	0	0	1
Pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	0
Peripheral swelling
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1	0	1	0	0	0	0	0	1
Thirst
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Seasonal allergy
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	1	0	0	1	1	0	0
Reproductive system and breast disorders
Atrophic vulvovaginitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0
Balanoposthitis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	2	0	0	0	0
Breast haematoma
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Endometrial hyperplasia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Epididymal cyst
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Menopausal symptoms
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Menorrhagia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Menstrual disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Metrorrhagia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0
Prostatomegaly
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Scrotal oedema
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Vaginal discharge
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Vulval disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	2 / 38 (5.26%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	4 / 77 (5.19%)	0 / 38 (0.00%)	1 / 39 (2.56%)	1 / 38 (2.63%)	2 / 76 (2.63%)	0 / 40 (0.00%)	3 / 38 (7.89%)
occurrences all number	0	1	0	4	0	1	1	2	0	3
Dysphonia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Epistaxis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Hydrothorax
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	0	1	0	0	0	0	0	0	1	2
Oropharyngeal pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 77 (1.30%)	0 / 38 (0.00%)	1 / 39 (2.56%)	2 / 38 (5.26%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	1	0	1	2	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Respiratory tract congestion
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0
Sinus congestion
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	1 / 76 (1.32%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	1	0
Sleep apnoea syndrome
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	1	0	0	0	1	0	0	0	0	1
Sneezing
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
Upper respiratory tract congestion
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	2 / 38 (5.26%)	3 / 77 (3.90%)	1 / 38 (2.63%)	1 / 39 (2.56%)	1 / 38 (2.63%)	1 / 76 (1.32%)	2 / 40 (5.00%)	2 / 38 (5.26%)
occurrences all number	1	0	2	3	1	1	1	1	2	2
Binge drinking
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Depression
subjects affected / exposed	1 / 38 (2.63%)	2 / 38 (5.26%)	1 / 38 (2.63%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	2 / 38 (5.26%)	1 / 76 (1.32%)	0 / 40 (0.00%)	2 / 38 (5.26%)
occurrences all number	1	2	1	1	0	0	2	1	0	2
Grief reaction
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	2 / 38 (5.26%)	2 / 77 (2.60%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	1	2	2	0	0	0	1	1	0
Organic brain syndrome
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Schizophrenia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Stress
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Product issues
Device dislocation
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Hepatobiliary disorders
Biliary dyskinesia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Cholelithiasis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	1	1	0	0	0	1
Hepatic steatosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	1	0	0	0	1	0	1
Investigations
Amylase decreased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Apolipoprotein A-I decreased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Blood albumin increased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	1 / 39 (2.56%)	1 / 38 (2.63%)	3 / 76 (3.95%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	0	0	1	0	1	1	5	0	0
Blood glucose increased
subjects affected / exposed	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
Blood magnesium decreased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0
Blood potassium decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Blood potassium increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	2	0
Blood uric acid increased
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Creatinine urine increased
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Electrocardiogram change
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0
Glomerular filtration rate decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Glomerular filtration rate increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Glycosylated haemoglobin increased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Haematocrit increased
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Haemoglobin increased
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Haemoglobin urine present
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Heart rate decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Heart rate irregular
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
High density lipoprotein decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Lipase abnormal
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0
Liver function test increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	1	0	0	0	0	0	1
Liver scan abnormal
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Prostatic specific antigen increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Protein urine present
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Serum ferritin decreased
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Urine albumin/creatinine ratio increased
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	3 / 38 (7.89%)	1 / 77 (1.30%)	5 / 38 (13.16%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	1	4	1	7	1	2	0	0	0
Urine leukocyte esterase
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Urine leukocyte esterase positive
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	1	2	0	2	1
Weight increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Anastomotic ulcer
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Animal bite
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Ankle fracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Contusion
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0
Epicondylitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0
Fall
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Foot fracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Hand fracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Joint injury
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Laceration
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Ligament rupture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Ligament sprain
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	3 / 38 (7.89%)	4 / 77 (5.19%)	2 / 38 (5.26%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	1	0	3	4	2	0	1	1	1	1
Limb injury
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Muscle rupture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Muscle strain
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	2	1	0	1	0	0	1	0	0
Post procedural complication
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Post procedural discomfort
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Post-traumatic pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Skin abrasion
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0
Tooth fracture
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Congenital, familial and genetic disorders
Porokeratosis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Type IIa hyperlipidaemia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Bundle branch block right
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Microvascular coronary artery disease
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Sinus tachycardia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Carpal tunnel syndrome
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	0	1	0	0	0	0	1	0	1	1
Dizziness
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	2 / 39 (5.13%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	2	0	0	1	0	2	1	0	1	0
Dizziness postural
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0
Facial paralysis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Headache
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	3 / 39 (7.69%)	1 / 38 (2.63%)	1 / 76 (1.32%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	3	2	0	2	0	3	1	1	1	4
Hypoaesthesia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0
Hyposmia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1	0	2	0	0	1	0	0	1
Nerve compression
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Sciatica
subjects affected / exposed	1 / 38 (2.63%)	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	2	0	0	1	0	0	0	0	0
Sinus headache
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Syncope
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	1	0
Tremor
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0
Iron deficiency anaemia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Neutropenia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Polycythaemia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
Thrombocytopenia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Thrombocytosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Eustachian tube dysfunction
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Inner ear disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Tympanic membrane perforation
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	1	2	0	0	1	1
Vertigo positional
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Eye disorders
Blepharospasm
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Cataract
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	2 / 38 (5.26%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	1	2	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Eye movement disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Eye pruritus
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Myopic chorioretinal degeneration
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Ulcerative keratitis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Vitreous floaters
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	3 / 38 (7.89%)	7 / 77 (9.09%)	3 / 38 (7.89%)	3 / 39 (7.69%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	4 / 38 (10.53%)
occurrences all number	3	1	4	7	3	6	0	0	1	5
Abdominal distension
subjects affected / exposed	3 / 38 (7.89%)	2 / 38 (5.26%)	4 / 38 (10.53%)	8 / 77 (10.39%)	9 / 38 (23.68%)	5 / 39 (12.82%)	4 / 38 (10.53%)	6 / 76 (7.89%)	6 / 40 (15.00%)	7 / 38 (18.42%)
occurrences all number	5	4	5	9	10	5	6	9	7	8
Abdominal pain
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	2 / 38 (5.26%)	3 / 77 (3.90%)	1 / 38 (2.63%)	3 / 39 (7.69%)	2 / 38 (5.26%)	2 / 76 (2.63%)	1 / 40 (2.50%)	4 / 38 (10.53%)
occurrences all number	3	2	2	4	1	3	2	2	1	5
Abdominal pain lower
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Abdominal pain upper
subjects affected / exposed	2 / 38 (5.26%)	3 / 38 (7.89%)	4 / 38 (10.53%)	7 / 77 (9.09%)	7 / 38 (18.42%)	3 / 39 (7.69%)	4 / 38 (10.53%)	4 / 76 (5.26%)	4 / 40 (10.00%)	4 / 38 (10.53%)
occurrences all number	6	3	6	12	9	3	10	10	4	6
Bowel movement irregularity
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Breath odour
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Change of bowel habit
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	3 / 77 (3.90%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0	0
Chronic gastritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Constipation
subjects affected / exposed	6 / 38 (15.79%)	7 / 38 (18.42%)	6 / 38 (15.79%)	11 / 77 (14.29%)	12 / 38 (31.58%)	5 / 39 (12.82%)	8 / 38 (21.05%)	8 / 76 (10.53%)	7 / 40 (17.50%)	9 / 38 (23.68%)
occurrences all number	7	9	6	12	14	5	11	8	9	15
Defaecation urgency
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	4 / 38 (10.53%)	7 / 77 (9.09%)	5 / 38 (13.16%)	1 / 39 (2.56%)	4 / 38 (10.53%)	3 / 76 (3.95%)	1 / 40 (2.50%)	3 / 38 (7.89%)
occurrences all number	0	0	4	11	6	1	6	3	2	4
Diarrhoea
subjects affected / exposed	14 / 38 (36.84%)	7 / 38 (18.42%)	15 / 38 (39.47%)	42 / 77 (54.55%)	16 / 38 (42.11%)	12 / 39 (30.77%)	14 / 38 (36.84%)	29 / 76 (38.16%)	14 / 40 (35.00%)	8 / 38 (21.05%)
occurrences all number	14	12	23	64	23	19	28	50	18	17
Diverticulum
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Dry mouth
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
Dyschezia
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	1	0	0	0	1	0	0	0	1	1
Dyspepsia
subjects affected / exposed	3 / 38 (7.89%)	1 / 38 (2.63%)	1 / 38 (2.63%)	1 / 77 (1.30%)	10 / 38 (26.32%)	5 / 39 (12.82%)	4 / 38 (10.53%)	6 / 76 (7.89%)	3 / 40 (7.50%)	10 / 38 (26.32%)
occurrences all number	3	1	1	2	14	9	6	9	3	10
Eosinophilic oesophagitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Eructation
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	2 / 38 (5.26%)	5 / 77 (6.49%)	5 / 38 (13.16%)	1 / 39 (2.56%)	3 / 38 (7.89%)	4 / 76 (5.26%)	2 / 40 (5.00%)	2 / 38 (5.26%)
occurrences all number	3	1	3	5	5	1	3	6	2	4
Faeces hard
subjects affected / exposed	2 / 38 (5.26%)	2 / 38 (5.26%)	2 / 38 (5.26%)	3 / 77 (3.90%)	5 / 38 (13.16%)	0 / 39 (0.00%)	2 / 38 (5.26%)	2 / 76 (2.63%)	1 / 40 (2.50%)	3 / 38 (7.89%)
occurrences all number	3	2	2	3	6	0	5	2	1	5
Flatulence
subjects affected / exposed	7 / 38 (18.42%)	9 / 38 (23.68%)	9 / 38 (23.68%)	21 / 77 (27.27%)	12 / 38 (31.58%)	6 / 39 (15.38%)	11 / 38 (28.95%)	21 / 76 (27.63%)	6 / 40 (15.00%)	8 / 38 (21.05%)
occurrences all number	11	11	11	27	20	9	15	24	6	9
Frequent bowel movements
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	1	0	1	0	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0
Gastrointestinal motility disorder
subjects affected / exposed	2 / 38 (5.26%)	2 / 38 (5.26%)	4 / 38 (10.53%)	3 / 77 (3.90%)	7 / 38 (18.42%)	0 / 39 (0.00%)	3 / 38 (7.89%)	2 / 76 (2.63%)	0 / 40 (0.00%)	4 / 38 (10.53%)
occurrences all number	4	2	4	3	9	0	5	3	0	7
Gastrointestinal pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Gastrointestinal sounds abnormal
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	4 / 38 (10.53%)	5 / 77 (6.49%)	4 / 38 (10.53%)	1 / 39 (2.56%)	4 / 38 (10.53%)	3 / 76 (3.95%)	1 / 40 (2.50%)	3 / 38 (7.89%)
occurrences all number	3	1	5	6	5	1	7	5	2	5
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	3 / 77 (3.90%)	2 / 38 (5.26%)	3 / 39 (7.69%)	1 / 38 (2.63%)	4 / 76 (5.26%)	1 / 40 (2.50%)	3 / 38 (7.89%)
occurrences all number	1	0	0	3	2	3	2	6	1	5
Glossodynia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Haemorrhoids
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	1	0	0	0	1	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	1	0	0	0	0	0	1
Large intestine polyp
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0
Melaena
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 38 (2.63%)	3 / 38 (7.89%)	3 / 38 (7.89%)	3 / 77 (3.90%)	8 / 38 (21.05%)	3 / 39 (7.69%)	3 / 38 (7.89%)	4 / 76 (5.26%)	5 / 40 (12.50%)	5 / 38 (13.16%)
occurrences all number	1	3	4	6	10	3	4	4	6	6
Splenic artery aneurysm
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Tooth disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Toothache
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	3 / 76 (3.95%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	2	0	0	0	3	0	1
Vomiting
subjects affected / exposed	3 / 38 (7.89%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	1 / 38 (2.63%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 76 (0.00%)	2 / 40 (5.00%)	1 / 38 (2.63%)
occurrences all number	5	0	1	0	1	2	0	0	2	1
Skin and subcutaneous tissue disorders
Dermal cyst
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Dermatitis allergic
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Eczema
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Hyperkeratosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0
Lichen sclerosus
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0
Pruritus
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Pustular psoriasis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Rash
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	2 / 76 (2.63%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	1	0	0	2	0	0
Rash maculo-papular
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0
Rosacea
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Skin fissures
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0
Dysuria
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	2	0	1	1	0	1
Haematuria
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 77 (2.60%)	1 / 38 (2.63%)	2 / 39 (5.13%)	2 / 38 (5.26%)	0 / 76 (0.00%)	3 / 40 (7.50%)	1 / 38 (2.63%)
occurrences all number	0	0	0	2	1	2	2	0	4	1
Hypertonic bladder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0
Lower urinary tract symptoms
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Microalbuminuria
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	2 / 38 (5.26%)	1 / 77 (1.30%)	3 / 38 (7.89%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	3 / 38 (7.89%)
occurrences all number	0	1	2	1	3	0	1	0	0	3
Pollakiuria
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	2 / 38 (5.26%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0	0
Proteinuria
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	1 / 38 (2.63%)	2 / 39 (5.13%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	3 / 38 (7.89%)
occurrences all number	1	0	1	0	1	2	1	0	0	3
Renal cyst
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	2 / 76 (2.63%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	1	0	0	2	0	0
Renal impairment
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	1	0	0	1
Urinary incontinence
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	6 / 77 (7.79%)	2 / 38 (5.26%)	2 / 39 (5.13%)	2 / 38 (5.26%)	2 / 76 (2.63%)	2 / 40 (5.00%)	2 / 38 (5.26%)
occurrences all number	2	1	0	6	3	3	2	2	3	5
Arthritis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	1	0	0	1	0	0	0
Back pain
subjects affected / exposed	3 / 38 (7.89%)	4 / 38 (10.53%)	1 / 38 (2.63%)	7 / 77 (9.09%)	2 / 38 (5.26%)	4 / 39 (10.26%)	3 / 38 (7.89%)	5 / 76 (6.58%)	3 / 40 (7.50%)	1 / 38 (2.63%)
occurrences all number	3	5	1	9	2	4	5	5	3	1
Bursitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Costochondritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Dupuytren's contracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Exostosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Extremity contracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Fibromyalgia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Flank pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Intervertebral disc protrusion
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	1	1	0	0	1	0	0
Joint effusion
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Joint swelling
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	1	0	0	0	0	1	0	0	1	1
Muscle spasms
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	2 / 40 (5.00%)	1 / 38 (2.63%)
occurrences all number	1	0	0	2	0	0	1	1	2	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	2 / 38 (5.26%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	2 / 40 (5.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	2	0
Myalgia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	1	0	1	0	0	1
Neck pain
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Osteoarthritis
subjects affected / exposed	2 / 38 (5.26%)	2 / 38 (5.26%)	0 / 38 (0.00%)	3 / 77 (3.90%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	2	3	0	3	1	0	1	0	1	1
Pain in extremity
subjects affected / exposed	3 / 38 (7.89%)	3 / 38 (7.89%)	1 / 38 (2.63%)	2 / 77 (2.60%)	0 / 38 (0.00%)	2 / 39 (5.13%)	1 / 38 (2.63%)	3 / 76 (3.95%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	3	3	1	2	0	2	1	3	0	1
Pain in jaw
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Plantar fasciitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	0	0
Scleroderma
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Spinal osteoarthritis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0
Spinal pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0
Tendon pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Tendonitis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	0
Tenosynovitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Trigger finger
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Bacterial vulvovaginitis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Balanitis candida
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Bronchitis
subjects affected / exposed	4 / 38 (10.53%)	0 / 38 (0.00%)	2 / 38 (5.26%)	2 / 77 (2.60%)	0 / 38 (0.00%)	2 / 39 (5.13%)	2 / 38 (5.26%)	2 / 76 (2.63%)	3 / 40 (7.50%)	2 / 38 (5.26%)
occurrences all number	4	0	2	2	0	2	2	3	3	2
Cellulitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0
Cystitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Cystitis bacterial
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	1	0
Ear infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0
Epiglottitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0
Eye infection
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Folliculitis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	1	0	0	0	0	0	0	1	0	1
Fungal infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	2 / 40 (5.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	1	0	1	0	0	2	1
Gastroenteritis viral
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	2 / 39 (5.13%)	1 / 38 (2.63%)	1 / 76 (1.32%)	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	1	0	0	2	0	2	1	1	1	1
Gastrointestinal viral infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Genital candidiasis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Genital herpes zoster
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Genital infection fungal
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 77 (2.60%)	1 / 38 (2.63%)	2 / 39 (5.13%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	2	2	2	0	1	0	0
Helicobacter infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Herpes simplex
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Hordeolum
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0
Influenza
subjects affected / exposed	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 38 (0.00%)	3 / 77 (3.90%)	5 / 38 (13.16%)	2 / 39 (5.13%)	2 / 38 (5.26%)	3 / 76 (3.95%)	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	2	0	0	4	6	2	2	4	1	2
Nasopharyngitis
subjects affected / exposed	4 / 38 (10.53%)	2 / 38 (5.26%)	3 / 38 (7.89%)	8 / 77 (10.39%)	4 / 38 (10.53%)	3 / 39 (7.69%)	7 / 38 (18.42%)	5 / 76 (6.58%)	0 / 40 (0.00%)	2 / 38 (5.26%)
occurrences all number	5	2	3	9	6	4	9	6	0	3
Onychomycosis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
Oral candidiasis
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	3	0	1	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0
Otitis externa
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0
Otitis externa fungal
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0
Paronychia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0
Pharyngitis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Pharyngitis streptococcal
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0
Pneumonia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0
Post procedural infection
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Pulpitis dental
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Rhinitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	3 / 77 (3.90%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	3	0	0	0	1	1	0
Sinobronchitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Sinusitis
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	3 / 38 (7.89%)	1 / 77 (1.30%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	3 / 76 (3.95%)	3 / 40 (7.50%)	0 / 38 (0.00%)
occurrences all number	1	1	3	1	1	0	1	3	3	0
Tinea pedis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
Tonsillitis
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	1	1	0	0	0	0	0	0	0	1
Tooth abscess
subjects affected / exposed	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	2	0	0	0	0	0	0	1	0	0
Tooth infection
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Tracheitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 38 (5.26%)	3 / 38 (7.89%)	3 / 38 (7.89%)	7 / 77 (9.09%)	2 / 38 (5.26%)	2 / 39 (5.13%)	1 / 38 (2.63%)	2 / 76 (2.63%)	5 / 40 (12.50%)	5 / 38 (13.16%)
occurrences all number	3	6	5	8	2	3	3	2	7	6
Urinary tract infection
subjects affected / exposed	3 / 38 (7.89%)	1 / 38 (2.63%)	3 / 38 (7.89%)	1 / 77 (1.30%)	1 / 38 (2.63%)	4 / 39 (10.26%)	4 / 38 (10.53%)	4 / 76 (5.26%)	2 / 40 (5.00%)	5 / 38 (13.16%)
occurrences all number	5	2	3	1	1	4	6	5	2	5
Urinary tract infection bacterial
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Vaginal infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	2 / 39 (5.13%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	2	0	2	0	2	0	0
Vestibular neuronitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Viral infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	3 / 38 (7.89%)
occurrences all number	0	0	0	1	0	2	0	0	0	5
Viral upper respiratory tract infection
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	2 / 77 (2.60%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	2	2	0	2	0	0	0	0	0	1
Vulvitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	2 / 76 (2.63%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	3 / 76 (3.95%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	1	0	1	0	0	1	3	1	0
Wound infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Appetite disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Decreased appetite
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0
Dehydration
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	1	1	0	0	1	0	0	1
Diabetes mellitus
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 76 (1.32%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0
Gout
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	2 / 38 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	3
Hypercholesterolaemia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	1 / 77 (1.30%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	2 / 76 (2.63%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	9	0	3	0	0	0	0	6	0	0
Hyperkalaemia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 38 (0.00%)	2 / 77 (2.60%)	1 / 38 (2.63%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	2	0	2	1	0	1	0	1	0
Hypoglycaemia
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 38 (0.00%)	3 / 77 (3.90%)	4 / 38 (10.53%)	2 / 39 (5.13%)	1 / 38 (2.63%)	1 / 76 (1.32%)	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	4	1	0	3	10	28	1	1	2	11
Hypokalaemia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Hypomagnesaemia
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Increased appetite
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Iron deficiency
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Ketosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Polydipsia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 77 (0.00%)	0 / 38 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 76 (0.00%)	0 / 40 (0.00%)	0 / 38 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 77 (0.00%)	1 / 38 (2.63%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 76 (0.00%)	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	0	0	0	1	0	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

19 Sep 2017

The protocol was amended to provide information related to a new risk recently identified from data of the SGLT-2 inhibitor canagliflozin where more cases of lower limb amputations (mainly of the toe) have been observed in the canagliflozin group compared to the placebo group. No lower limb amputations were seen in LIK066 studies, but this risk may constitute a possible class-effect. Patients with a history of lower limb amputation were excluded from enrollment into the study. As a precautionary measure, patients with any history of ketoacidosis, lactic acidosis, or hyperosmolar coma were excluded from enrollment into the study as well. Furthermore, some minor changes and corrections of inconsistencies and typographical errors have been done.This amendment was not considered to have affected the interpretation of study results.

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 randomized, double-blind, dose-finding study to evaluate the change in weight after 24 weeks treatment with 8 doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent change from baseline in body weight at 24 weeks

Primary: Percent change from baseline in body weight at 24 weeks

Secondary: Number of subjects with response rate according to percent decrease in body weight for overall study

Secondary: Number of subjects with response rate according to percent decrease in body weight for overall study

Secondary: Number of subjects with response rate according to percent decrease in body weight for Subgroups

Secondary: Number of subjects with response rate according to percent decrease in body weight for Subgroups

Secondary: Change from baseline on waist circumference

Secondary: Change from baseline on waist circumference

Secondary: Change from baseline in fasting plasma glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)

Secondary: Change from baseline in fasting plasma glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)

Secondary: Change from baseline in glycated hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus patients (T2DM)

Secondary: Change from baseline in glycated hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus patients (T2DM)

Secondary: Change from baseline in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP)

Secondary: Change from baseline in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP)

Secondary: Change from baseline in 24-hour urinary glucose excretion

Secondary: Change from baseline in 24-hour urinary glucose excretion

Secondary: Change in Weight in the overall population and by subgroups (Epoch 4)

Secondary: Change in Weight in the overall population and by subgroups (Epoch 4)

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary calcium excretion

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary calcium excretion

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary calcium excretion

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary calcium excretion

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary phosphorus excretion

Secondary: Change from Baseline to Week 24 (Epoch 3) in the 24-hour urinary phosphorus excretion

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary phosphorus excretion

Secondary: Change from Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour urinary phosphorus excretion

Secondary: Change from baseline in fasting lipid profile (lipoproteins)

Secondary: Change from baseline in fasting lipid profile (lipoproteins)

Secondary: Change from baseline in High sensitive C-reactive protein (hsCRP)

Secondary: Change from baseline in High sensitive C-reactive protein (hsCRP)

Secondary: Change from baseline in fasting lipid profile (triglycerides/cholesterol)

Secondary: Change from baseline in fasting lipid profile (triglycerides/cholesterol)

Secondary: Pharmacokinetics of LIK066: Observe maximum plasma concentration (cmax)

Secondary: Pharmacokinetics of LIK066: Observe maximum plasma concentration (cmax)

Secondary: Pharmacokinetics of LIK066: Time to reach the maximum concentration (Tmax)

Secondary: Pharmacokinetics of LIK066: Time to reach the maximum concentration (Tmax)

Secondary: Pharmacokinetics of LIK066: Area under the plasma concentration-time curve from time zero time 't' (AUC0-t)

Secondary: Pharmacokinetics of LIK066: Area under the plasma concentration-time curve from time zero time 't' (AUC0-t)

Secondary: Pharmacokinetics of LIK066: Last non-zero concentration area under the curve (AUClast)

Secondary: Pharmacokinetics of LIK066: Last non-zero concentration area under the curve (AUClast)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A randomized, double-blind, dose-finding study to evaluate the change in weight after 24 weeks treatment with 8 doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo