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Clinical Trial Results:
A randomized, double-blind, multi-dose, placebo-controlled study to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus in patients with primary biliary cholangitis (GLIMMER: GSK2330672 triaL of Ibat inhibition with Multidose Measurement for Evaluation of Response)

Summary
EudraCT number	2016-002416-41
Trial protocol	ES GB PL IT
Global end of trial date	15 Apr 2020

Results information
Results version number	v1(current)
This version publication date	24 Apr 2021
First version publication date	24 Apr 2021
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

201000

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.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

30 Jul 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Apr 2020

Was the trial ended prematurely?

Main objective of the trial

To investigate the dose response of oral GSK2330672 on itch in primary biliary cholangitis (PBC) participants with moderate to severe pruritus at Baseline

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jan 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 4

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

France: 8

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Japan: 38

Country: Number of subjects enrolled

Poland: 17

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

United Kingdom: 25

Country: Number of subjects enrolled

United States: 20

Worldwide total number of subjects

147

EEA total number of subjects

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)

111

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

This study was conducted across 66 centers in 10 countries. The 40 milligrams (mg) twice daily dose group was added and recruitment into the 20 mg twice daily dose group was discontinued following the pre-specified interim analysis.

Screening details

A total of 147 adult participants were randomized in this study.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 16 weeks including the Main Study Period and Final Study period. Participants were then followed up for 4 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

GSK2330672 20 mg QD

Arm description

Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period followed by matching placebo for 4 weeks in the Final Study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

Arm type

Experimental

Investigational medicinal product name

GSK2330672

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

GSK2330672 90 mg QD

Arm description

Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

Arm type

Experimental

Investigational medicinal product name

GSK2330672

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

GSK2330672 180 mg QD

Arm description

Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

Arm type

Experimental

Investigational medicinal product name

GSK2330672

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

GSK2330672 40 mg BID

Arm description

Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

Arm type

Experimental

Investigational medicinal product name

GSK2330672

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

GSK2330672 90 mg BID

Arm description

Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks All doses were administered via oral route.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was available as white-film coated tablets to be administered orally.

Investigational medicinal product name

GSK2330672

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

Number of subjects in period 1	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Started	36	16	23	27	23	22
Completed	35	16	22	22	22	21
Not completed	1	0	1	5	1	1
Consent withdrawn by subject	-	-	-	2	-	-
Adverse event, non-fatal	-	-	1	2	1	1
Lack of efficacy	1	-	-	-	-	-
Protocol deviation	-	-	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

GSK2330672 20 mg QD

Reporting group description

Reporting group title

GSK2330672 90 mg QD

Reporting group description

Reporting group title

GSK2330672 180 mg QD

Reporting group description

Reporting group title

GSK2330672 40 mg BID

Reporting group description

Reporting group title

GSK2330672 90 mg BID

Reporting group description

Reporting group values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID	Total
Number of subjects	36	16	23	27	23	22	147
Age categorical
Units: Subjects
All participants	36	16	23	27	23	22	147
Age Continuous
Units: Years
arithmetic mean (standard deviation)	54.4 ± 11.06	58.5 ± 7.35	52.5 ± 12.32	58.9 ± 11.10	55.6 ± 11.23	56.2 ± 11.32	-
Sex: Female, Male
Units: Participants
Female	34	16	21	25	22	20	138
Male	2	0	2	2	1	2	9
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaskan Native	0	0	0	0	1	0	1
Asian - Japanese Heritage	8	6	6	7	4	7	38
White - White/Caucasian/European Heritage	26	10	17	19	16	15	103
Multiple	0	0	0	1	0	0	1
Unknown	2	0	0	0	2	0	4

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

GSK2330672 20 mg QD

Reporting group description

Reporting group title

GSK2330672 90 mg QD

Reporting group description

Reporting group title

GSK2330672 180 mg QD

Reporting group description

Reporting group title

GSK2330672 40 mg BID

Reporting group description

Reporting group title

GSK2330672 90 mg BID

Reporting group description

Subject analysis set title

Placebo -Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 12 weeks in Main Study Period.

Subject analysis set title

GSK2330672 20 mg QD - Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period.

Subject analysis set title

GSK2330672 90 mg QD - Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period.

Subject analysis set title

GSK2330672 180 mg QD - Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period.

Subject analysis set title

GSK2330672 40 mg BID - Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period.

Subject analysis set title

GSK2330672 90 mg BID - Main Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period

Subject analysis set title

Placebo - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period.

Subject analysis set title

GSK2330672 20 mg QD - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 20 mg QD during Main study period.

Subject analysis set title

GSK2330672 90 mg QD - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 90 mg QD during Main study period.

Subject analysis set title

GSK2330672 180 mg QD - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 180 mg QD during Main study period.

Subject analysis set title

GSK2330672 40 mg BID - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 40 mg BID during Main study period.

Subject analysis set title

GSK2330672 90 mg BID - Final Study Period

Subject analysis set type

Sub-group analysis

Subject analysis set description

Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 90 mg BID during Main study period.

Subject analysis set title

Placebo - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received GSK2330672 matching placebo in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Subject analysis set title

GSK2330672 20 mg QD - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Subject analysis set title

GSK2330672 90 mg QD - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Subject analysis set title

GSK2330672 180 mg QD - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Subject analysis set title

GSK2330672 40 mg BID - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Subject analysis set title

GSK2330672 90 mg BID - Follow-up

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

Primary: Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score

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End point title

Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score

End point description

Participants were required to score the severity of their itching using a 0-10 numerical rating scale (NRS) where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the average of the scores in the 7 days prior to the Week 4 (Visit 3 [V3]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was done using Analysis of covariance (ANCOVA) including treatment group and centered Mean Worst Daily Itch score at Baseline. Intent-to-Treat (ITT) Population comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one on-treatment assessment. Only those participants with data available at the specified data points were analyzed.

End point type

Primary

End point timeframe

Baseline and Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[1]	16 ^[2]	20 ^[3]	22 ^[4]	22 ^[5]	21 ^[6]
Units: Scores on a scale
least squares mean (confidence interval 95%)	-1.73 (-2.44 to -1.01)	-2.19 (-3.26 to -1.12)	-2.60 (-3.55 to -1.65)	-2.60 (-3.51 to -1.70)	-2.86 (-3.76 to -1.95)	-2.25 (-3.19 to -1.32)

Notes
[1] - ITT Population
[2] - ITT Population
[3] - ITT Population
[4] - ITT Population
[5] - ITT Population
[6] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.75

upper limit

0.82

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

0.31

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-2.03

upper limit

0.28

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-2.29

upper limit

0.03

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

0.65

Secondary: Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale

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End point title

Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale

End point description

PBC-40 questionnaire consists of 40 questions arranged in 6 domains with 3 to 11 questions in each domain. Each question is scored from 1 (least impact) to 5 (greatest impact). All questions within a domain are summed to obtain individual domain score. Domains were: Symptoms (7 questions) with score range 7-35, Itch (3 questions) with score range 3-15, Fatigue (11 questions) with score range 11-55, Cognitive (6 questions) with score range 6-30, Emotional (3 questions) with score range 3-15, and Social (10 questions) with score range 10-50. Higher scores for individual domains represent a poor quality of life. Baseline is the assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[7]	16 ^[8]	21 ^[9]	22 ^[10]	22 ^[11]	20 ^[12]
Units: Scores on a scale
least squares mean (confidence interval 95%)
Symptoms	0.2 (-1.0 to 1.4)	0.4 (-1.3 to 2.2)	0.7 (-0.8 to 2.3)	-0.9 (-2.4 to 0.6)	0.3 (-1.2 to 1.8)	0.2 (-1.4 to 1.8)
Itch	-2.3 (-3.3 to -1.4)	-1.9 (-3.3 to -0.4)	-2.6 (-3.9 to -1.3)	-2.7 (-3.9 to -1.4)	-3.4 (-4.6 to -2.1)	-2.7 (-4.0 to -1.4)
Fatigue	-1.8 (-4.0 to 0.4)	-2.4 (-5.6 to 0.7)	-1.1 (-3.8 to 1.7)	1.7 (-1.0 to 4.5)	-0.1 (-2.8 to 2.6)	-1.8 (-4.6 to 1.1)
Cognitive	-0.3 (-1.7 to 1.1)	-0.3 (-2.4 to 1.8)	-0.9 (-2.7 to 0.9)	-0.1 (-1.9 to 1.6)	0.1 (-1.6 to 1.9)	-0.1 (-2.0 to 1.7)
Emotional	-0.5 (-1.2 to 0.1)	-1.4 (-2.4 to -0.4)	-0.4 (-1.3 to 0.5)	-0.6 (-1.5 to 0.3)	-1.4 (-2.2 to -0.5)	-0.6 (-1.5 to 0.3)
Social	-0.8 (-2.3 to 0.8)	-0.5 (-2.7 to 1.8)	0.4 (-1.5 to 2.4)	-0.6 (-2.5 to 1.3)	-3.1 (-5.1 to -1.2)	-1.0 (-3.0 to 1.0)

Notes
[7] - ITT Population
[8] - ITT Population
[9] - ITT Population
[10] - ITT Population
[11] - ITT Population
[12] - ITT Population

Statistical Analysis 1

Statistical analysis description

Symptoms

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

2.3

Statistical Analysis 2

Statistical analysis description

Symptoms

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.5

Statistical Analysis 3

Statistical analysis description

Symptoms

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

0.8

Statistical Analysis 4

Statistical analysis description

Symptoms

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

Statistical Analysis 5

Statistical analysis description

Symptoms

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

1.9

Statistical Analysis 6

Statistical analysis description

Itch

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

2.2

Statistical Analysis 7

Statistical analysis description

Itch

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

1.3

Statistical Analysis 8

Statistical analysis description

Itch

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.2

Statistical Analysis 9

Statistical analysis description

Itch

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

0.5

Statistical Analysis 10

Statistical analysis description

Itch

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.3

Statistical Analysis 11

Statistical analysis description

Fatigue

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

3.2

Statistical Analysis 12

Statistical analysis description

Fatigue

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

4.2

Statistical Analysis 13

Statistical analysis description

Fatigue

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Statistical Analysis 14

Statistical analysis description

Fatigue

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

5.1

Statistical Analysis 15

Statistical analysis description

Fatigue

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

3.6

Statistical Analysis 16

Statistical analysis description

Cognitive

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

2.6

Statistical Analysis 17

Statistical analysis description

Cognitive

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

1.7

Statistical Analysis 18

Statistical analysis description

Cognitive

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.5

Statistical Analysis 19

Statistical analysis description

Cognitive

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

2.8

Statistical Analysis 20

Statistical analysis description

Cognitive

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

2.5

Statistical Analysis 21

Statistical analysis description

Emotional

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.4

Statistical Analysis 22

Statistical analysis description

Emotional

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.3

Statistical Analysis 23

Statistical analysis description

Emotional

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.1

Statistical Analysis 24

Statistical analysis description

Emotional

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.3

Statistical Analysis 25

Statistical analysis description

Emotional

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.1

Statistical Analysis 26

Statistical analysis description

Social

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Statistical Analysis 27

Statistical analysis description

Social

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

3.7

Statistical Analysis 28

Statistical analysis description

Social

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

2.7

Statistical Analysis 29

Statistical analysis description

Social

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

0.1

Statistical Analysis 30

Statistical analysis description

Social

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.4

Secondary: Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression

End point description

Criteria for high risk of PBC progression is defined as serum ALP concentrations more than or equal to (>=)1.67 times upper limit of normal (ULN) range and/or total bilirubin concentrations more than (>)ULN at Day 1. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. High Risk Population comprised of subset of the ITT population who were assigned to the High Risk stratum for randomization (based upon serum ALP concentrations >=1.67 times ULN and/or total bilirubin concentrations >ULN at Day 1 (Visit 2). Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[13]	5 ^[14]	11 ^[15]	7 ^[16]	6 ^[17]	5 ^[18]
Units: International units per Liter
least squares mean (confidence interval 95%)	49.1 (-29.3 to 127.6)	-57.7 (-179.6 to 64.3)	-38.2 (-117.0 to 40.5)	49.6 (-49.1 to 148.2)	-29.2 (-136.7 to 78.3)	19.1 (-97.7 to 136.0)

Notes
[13] - High Risk Population
[14] - High Risk Population
[15] - High Risk Population
[16] - High Risk Population
[17] - High Risk Population
[18] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-106.8

Confidence interval

level

95%

sides

2-sided

lower limit

-251.7

upper limit

38.2

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-87.4

Confidence interval

level

95%

sides

2-sided

lower limit

-198.5

upper limit

23.8

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-125.6

upper limit

126.5

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-78.3

Confidence interval

level

95%

sides

2-sided

lower limit

-211.5

upper limit

54.8

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-30

Confidence interval

level

95%

sides

2-sided

lower limit

-170.7

upper limit

110.7

Secondary: Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16

Top of page

End point title

Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16

End point description

Number of participants with ALP < 1.67 times ULN and total bilirubin <= ULN at Week 16 is presented. The endpoint was analyzed in Restricted High Risk Population. Restricted High Risk Population comprised of a subset of the High Risk population, i.e. all those participants assigned to the High Risk stratum for randomization who met the ALP/bilirubin criteria at both Visit 2 (Day 1) and Visit 3 (Week 4).

End point type

Secondary

End point timeframe

At Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[19]	5 ^[20]	9 ^[21]	9 ^[22]	6 ^[23]	7 ^[24]
Units: Participants	0	0	0	0	0	1

Notes
[19] - Restricted High Risk Population
[20] - Restricted High Risk Population
[21] - Restricted High Risk Population
[22] - Restricted High Risk Population
[23] - Restricted High Risk Population
[24] - Restricted High Risk Population

No statistical analyses for this end point

Secondary: Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[25]	5 ^[26]	11 ^[27]	7 ^[28]	6 ^[29]	5 ^[30]
Units: International Units per Liter
least squares mean (confidence interval 95%)	13.0 (-7.9 to 33.9)	-8.4 (-39.5 to 22.7)	0.3 (-20.7 to 21.2)	-2.0 (-29.0 to 25.1)	-13.5 (-42.8 to 15.9)	13.2 (-17.4 to 43.7)

Notes
[25] - High Risk Population
[26] - High Risk Population
[27] - High Risk Population
[28] - High Risk Population
[29] - High Risk Population
[30] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-21.4

Confidence interval

level

95%

sides

2-sided

lower limit

-58.4

upper limit

15.5

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-12.7

Confidence interval

level

95%

sides

2-sided

lower limit

-41.9

upper limit

16.4

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-15

Confidence interval

level

95%

sides

2-sided

lower limit

-49.9

upper limit

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-26.5

Confidence interval

level

95%

sides

2-sided

lower limit

-63.3

upper limit

10.4

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-36.7

upper limit

37.1

Secondary: Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[31]	5 ^[32]	11 ^[33]	7 ^[34]	6 ^[35]	5 ^[36]
Units: International Units per Liter
least squares mean (confidence interval 95%)	13.96 (-4.55 to 32.46)	-6.04 (-34.20 to 22.12)	-10.75 (-28.90 to 7.40)	-8.66 (-32.24 to 14.93)	-17.72 (-42.77 to 7.34)	8.16 (-18.72 to 35.04)

Notes
[31] - High Risk Population
[32] - High Risk Population
[33] - High Risk Population
[34] - High Risk Population
[35] - High Risk Population
[36] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-52.73

upper limit

12.74

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-24.7

Confidence interval

level

95%

sides

2-sided

lower limit

-50.8

upper limit

1.39

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-22.61

Confidence interval

level

95%

sides

2-sided

lower limit

-53.39

upper limit

8.16

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-31.67

Confidence interval

level

95%

sides

2-sided

lower limit

-63.44

upper limit

0.09

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-5.79

Confidence interval

level

95%

sides

2-sided

lower limit

-38.33

upper limit

26.74

Secondary: Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[37]	5 ^[38]	11 ^[39]	7 ^[40]	6 ^[41]	5 ^[42]
Units: International Units per Liter
least squares mean (confidence interval 95%)	47.5 (-9.9 to 104.8)	-58.5 (-142.5 to 25.5)	-18.0 (-74.9 to 38.9)	4.6 (-66.5 to 75.8)	-18.4 (-93.6 to 56.8)	-6.7 (-89.1 to 75.8)

Notes
[37] - High Risk Population
[38] - High Risk Population
[39] - High Risk Population
[40] - High Risk Population
[41] - High Risk Population
[42] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-106

Confidence interval

level

95%

sides

2-sided

lower limit

-205.1

upper limit

-6.8

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-65.5

Confidence interval

level

95%

sides

2-sided

lower limit

-148.5

upper limit

17.6

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-42.8

Confidence interval

level

95%

sides

2-sided

lower limit

-136.5

upper limit

50.9

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-65.8

Confidence interval

level

95%

sides

2-sided

lower limit

-161.2

upper limit

29.5

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-54.1

Confidence interval

level

95%

sides

2-sided

lower limit

-153.6

upper limit

45.3

Secondary: Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[43]	5 ^[44]	11 ^[45]	7 ^[46]	6 ^[47]	5 ^[48]
Units: Micromoles per Liter
least squares mean (confidence interval 95%)	1.258 (-2.068 to 4.583)	-4.841 (-9.693 to 0.011)	-1.079 (-4.345 to 2.187)	-0.975 (-5.150 to 3.201)	-0.234 (-4.914 to 4.446)	6.494 (1.622 to 11.365)

Notes
[43] - High Risk Population
[44] - High Risk Population
[45] - High Risk Population
[46] - High Risk Population
[47] - High Risk Population
[48] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-6.099

Confidence interval

level

95%

sides

2-sided

lower limit

-11.929

upper limit

-0.268

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-2.337

Confidence interval

level

95%

sides

2-sided

lower limit

-6.962

upper limit

2.289

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-2.232

Confidence interval

level

95%

sides

2-sided

lower limit

-7.679

upper limit

3.215

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.492

Confidence interval

level

95%

sides

2-sided

lower limit

-7.413

upper limit

4.43

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

5.236

Confidence interval

level

95%

sides

2-sided

lower limit

-0.591

upper limit

11.063

Secondary: Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	11 ^[49]	5 ^[50]	11 ^[51]	7 ^[52]	6 ^[53]	5 ^[54]
Units: Grams per Liter
least squares mean (confidence interval 95%)	0.0 (-1.2 to 1.3)	-0.5 (-2.3 to 1.3)	0.3 (-1.0 to 1.6)	0.8 (-0.8 to 2.3)	0.0 (-1.7 to 1.7)	0.7 (-1.1 to 2.5)

Notes
[49] - High Risk Population
[50] - High Risk Population
[51] - High Risk Population
[52] - High Risk Population
[53] - High Risk Population
[54] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

1.6

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.1

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

2.7

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.9

Secondary: Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression

Top of page

End point title

Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	9 ^[55]	5 ^[56]	11 ^[57]	6 ^[58]	7 ^[59]	5 ^[60]
Units: Ratio
least squares mean (confidence interval 95%)	0.01 (-0.03 to 0.05)	-0.01 (-0.06 to 0.04)	-0.03 (-0.06 to 0.00)	0.01 (-0.04 to 0.05)	-0.02 (-0.07 to 0.02)	-0.03 (-0.08 to 0.02)

Notes
[55] - High Risk Population
[56] - High Risk Population
[57] - High Risk Population
[58] - High Risk Population
[59] - High Risk Population
[60] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.04

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.01

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.05

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.02

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.02

Secondary: Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression

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End point title

Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	9 ^[61]	5 ^[62]	11 ^[63]	6 ^[64]	7 ^[65]	5 ^[66]
Units: Seconds
least squares mean (confidence interval 95%)	-0.10 (-0.40 to 0.20)	0.05 (-0.33 to 0.44)	-0.21 (-0.47 to 0.05)	0.02 (-0.33 to 0.37)	-0.18 (-0.51 to 0.15)	-0.17 (-0.55 to 0.22)

Notes
[61] - High Risk Population
[62] - High Risk Population
[63] - High Risk Population
[64] - High Risk Population
[65] - High Risk Population
[66] - High Risk Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.63

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

0.3

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.58

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.38

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.41

Secondary: Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period

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End point title

Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE. Safety Population comprised of all randomized participants who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Up to 12 weeks

End point values	Placebo -Main Study Period	GSK2330672 20 mg QD - Main Study Period	GSK2330672 90 mg QD - Main Study Period	GSK2330672 180 mg QD - Main Study Period	GSK2330672 40 mg BID - Main Study Period	GSK2330672 90 mg BID - Main Study Period
Number of subjects analysed	36 ^[67]	16 ^[68]	23 ^[69]	27 ^[70]	23 ^[71]	22 ^[72]
Units: Participants
Any non-SAE	17	11	19	24	16	18
Any SAE	0	0	1	0	0	0

Notes
[67] - Safety Population
[68] - Safety Population
[69] - Safety Population
[70] - Safety Population
[71] - Safety Population
[72] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with non-SAEs and SAEs -Final study period

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End point title

Number of participants with non-SAEs and SAEs -Final study period

End point description

End point type

Secondary

End point timeframe

Up to 4 weeks

End point values	Placebo - Final Study Period	GSK2330672 20 mg QD - Final Study Period	GSK2330672 90 mg QD - Final Study Period	GSK2330672 180 mg QD - Final Study Period	GSK2330672 40 mg BID - Final Study Period	GSK2330672 90 mg BID - Final Study Period
Number of subjects analysed	35 ^[73]	16 ^[74]	19 ^[75]	19 ^[76]	21 ^[77]	17 ^[78]
Units: Participants
Any non-SAE	2	6	8	2	2	2
Any SAE	0	0	0	0	0	0

Notes
[73] - Safety Population
[74] - Safety Population
[75] - Safety Population
[76] - Safety Population
[77] - Safety Population
[78] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with non-SAEs and SAEs - Follow-up period

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End point title

Number of participants with non-SAEs and SAEs - Follow-up period

End point description

End point type

Secondary

End point timeframe

Up to 4 weeks

End point values	Placebo - Follow-up	GSK2330672 20 mg QD - Follow-up	GSK2330672 90 mg QD - Follow-up	GSK2330672 180 mg QD - Follow-up	GSK2330672 40 mg BID - Follow-up	GSK2330672 90 mg BID - Follow-up
Number of subjects analysed	35 ^[79]	16 ^[80]	23 ^[81]	27 ^[82]	22 ^[83]	22 ^[84]
Units: Participants
Any non-SAE	0	0	0	0	0	0
Any SAE	0	1	0	1	0	0

Notes
[79] - Safety Population
[80] - Safety Population
[81] - Safety Population
[82] - Safety Population
[83] - Safety Population
[84] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with clinical chemistry data of potential clinical importance

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End point title

Number of participants with clinical chemistry data of potential clinical importance

End point description

Blood samples were collected to measure analyze the following parameters: albumin, calcium, Glomerular filtration rate (GFR) from creatinine, glucose, potassium and sodium. Participants were counted in the worst case category that their value changes to (low, within range [w/in] or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100 percent (%). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Only “To Low” and/or “To High” categories with potential clinical importance data have been presented.

End point type

Secondary

End point timeframe

At Weeks 8, 12, 16 and 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[85]	16 ^[86]	23 ^[87]	27 ^[88]	23 ^[89]	22 ^[90]
Units: Participants
Albumin, To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Albumin, To Low, Week 12, n=35, 16, 21, 23, 22, 21	0	0	0	0	0	0
Albumin, To Low, Week 16, n=35, 16, 21, 22, 21, 20	0	0	0	0	0	0
Albumin, To Low, Week 20, n=35, 16, 22, 22, 22, 21	0	0	0	0	0	0
Calcium, To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Calcium, To High, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Calcium, To Low, Week 12, n=35, 16, 21, 23, 22, 21	0	0	0	0	0	0
Calcium, To High, Week 12, n=35, 16, 21, 23, 22,21	0	0	0	0	0	0
Calcium, To Low, Week 16, n=35, 16, 21, 22, 21, 20	0	0	0	0	0	0
Calcium, To High, Week 16,n=35, 16, 21, 22, 21, 20	0	0	0	0	0	0
Calcium, To Low, Week 20, n=35,16, 22, 22, 22, 21	0	0	0	0	0	0
Calcium, To High, Week 20, n=35,16, 22, 22, 22, 21	1	0	0	0	0	0
GFR, To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
GFR, To Low, Week 12, n=35, 15, 21, 23, 22, 21	0	0	0	0	0	0
GFR, To Low, Week 16, n=35, 16, 21, 22, 21, 21	0	0	0	0	0	0
GFR, To Low, Week 20, n=35, 16, 22, 22, 22, 21	0	0	0	1	0	0
Glucose ,To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Glucose ,To High, Week 8, n=36, 16, 21, 21, 22, 19	1	0	0	0	0	1
Glucose ,To Low, Week 12, n=35, 16, 21, 23, 22, 21	0	0	0	0	0	0
Glucose, To High, Week 12, n=35,16, 21, 23, 22, 21	0	0	0	0	0	0
Glucose ,To Low, Week 16, n=35, 16, 21, 22, 21,20	0	0	0	0	0	0
Glucose, To High, Week 16, n=35,16, 21, 22, 21, 20	0	0	0	0	0	0
Glucose ,To Low, Week 20, n=35, 16, 22, 22, 22, 21	0	0	0	0	0	0
Glucose, To High, Week 20, n=35,16, 22, 22, 22, 21	1	0	0	0	0	0
Potassium,To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Potassium, To High, Week 8, n=36,16, 21, 21, 22,19	0	0	0	0	0	0
Potassium,To Low, Week 12, n=35,16, 21, 23, 22, 21	0	0	0	0	0	0
Potassium,To High, Week 12,n=35,16, 21, 23, 22, 21	0	0	0	0	0	0
Potassium,To Low, Week 16, n=35,16, 21, 22, 21, 20	0	0	0	0	0	0
Potassium, To High, Week 16, n=35,16,21, 22, 21,20	0	0	0	0	0	0
Potassium,To Low, Week 20, n=35,16, 22, 22, 22, 21	0	0	0	0	0	0
Potassium, To High,Week 20, n=35,16, 22,22, 22, 21	0	0	0	0	0	0
Sodium, To Low, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Sodium, To High, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	0	0	0
Sodium, To Low, Week 12, n=35, 16, 21, 23, 22, 21	0	0	0	0	0	0
Sodium, To High, Week 12, n=35,16, 21, 23, 22, 21	0	0	0	0	0	0
Sodium, To Low, Week 16, n=35, 16, 21, 22, 21, 20	0	0	0	0	0	0
Sodium, To High, Week 16, n=35,16, 21, 22, 21, 20	0	0	1	0	0	0
Sodium, To Low, Week 20, n=35, 16, 22, 22, 22, 21	0	0	0	0	0	0
Sodium, To High, Week 20, n=35,16, 22, 22, 22, 21	0	0	0	0	0	0

Notes
[85] - Safety Population
[86] - Safety Population
[87] - Safety Population
[88] - Safety Population
[89] - Safety Population
[90] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with hematology data of potential clinical importance

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End point title

Number of participants with hematology data of potential clinical importance

End point description

Blood samples were collected to analyze the following parameters: hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Participants were counted in the worst case category that their value changes to (low, w/in or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Only “To Low” and/or “To High” categories with potential clinical importance data have been presented.

End point type

Secondary

End point timeframe

At Weeks 8, 12, 16 and 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[91]	16 ^[92]	23 ^[93]	27 ^[94]	23 ^[95]	22 ^[96]
Units: Participants
Hematocrit, To High, Week 8,n=36,16,21, 21, 22, 19	0	0	0	0	0	0
Hematocrit,To High, Week 12, n=33,15,21, 23, 22,20	0	0	0	0	0	0
Hematocrit,To High, Week 16, n=35,15,21,22,21,21	0	0	0	0	0	0
Hematocrit,To High, Week 20, n=34,16,22,22,22,20	0	0	0	0	0	0
Hemoglobin, To High, Week 8,n=36,16, 21,21, 22,19	0	0	0	0	0	0
Hemoglobin, To High, Week 12, n=33,15,21,23,22,20	0	0	0	0	0	0
Hemoglobin, To High, Week 16, n=35,15,21,22,21,21	0	0	0	0	0	0
Hemoglobin, To High, Week 20, n=34,16, 22,22,22,20	0	0	0	0	0	0
Leukocytes, To Low, Week 8, n=36,15, 21,21, 22,19	1	0	0	0	1	0
Leukocytes,To High, Week 8, n=36,15,21,21,22,19	0	0	0	0	0	0
Leukocytes,To Low,Week 12, n=33,15,21,23,22,20	1	1	1	0	0	0
Leukocytes,To High, Week 12, n=33,15,21,23, 22,20	0	0	0	0	0	0
Leukocytes, To Low, Week 16, n=34,15,21, 22, 20,21	1	0	3	1	1	0
Leukocytes,To High, Week 16, n=34,15,21,22, 20,21	0	0	0	0	0	0
Leukocytes, To Low, Week 20, n=34,16,22,21,22,19	0	1	1	0	0	0
Leukocytes, To High, Week 20, n=34,16,22,21,22,19	0	0	0	0	0	0
Lymphocytes, To Low, Week 8, n=35,15,21,21,22,19	2	0	0	0	0	0
Lymphocytes, To Low, Week 12, n=32,15,21,23,22,20	1	0	0	2	0	0
Lymphocytes, To Low, Week 16, n=34,15,21,22,20,21	0	0	0	1	0	0
Lymphocytes, To Low, Week 20, n=34,16,22,21,22,19	0	0	1	0	0	0
Neutrophils, To Low, Week 8,n=35,15,21,21,22,19	1	1	0	1	1	1
Neutrophils, To Low, Week 12, n=32,15,21,23,22,20	0	1	0	1	0	1
Neutrophils, To Low, Week 16, n=34,15,21,22,20,21	1	0	2	0	1	0
Neutrophils, To Low, Week 20, n=34,16,22,21,22,19	0	0	1	0	0	0
Platelets, To Low, Week 8,n=36,15,20,21,22,19	0	0	0	0	0	0
Platelets, To High, Week 8,n=36,15,20,21,22,19	0	0	0	0	0	0
Platelets, To Low, Week 12, n=33,14,19,23,22,20	0	0	0	0	0	1
Platelets,To High, Week 12, n=33,14,19,23,22,20	0	0	0	0	0	0
Platelets, To Low, Week 16, n=35,14,19,22, 21,21	1	0	0	0	0	1
Platelets,To High, Week 16, n=35,14,19,22, 21,21	1	0	0	0	0	0
Platelets, To Low, Week 20, n=33,16,21,21,22,20	0	0	0	0	0	0
Platelets,To High, Week 20, n=33,16,21,21,22,20	0	0	0	0	0	0

Notes
[91] - Safety Population
[92] - Safety Population
[93] - Safety Population
[94] - Safety Population
[95] - Safety Population
[96] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters

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End point title

Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters

End point description

A 12-lead ECG was recorded with the participant in a semi-supine position. 12-lead ECGs were obtained by using an automated ECG machine. Data for abnormal, not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

At Weeks 8, 12, 16 and 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[97]	16 ^[98]	23 ^[99]	27 ^[100]	23 ^[101]	22 ^[102]
Units: Participants
Abnormal, NCS, Week 8, n=36, 16, 21, 21, 22,19	10	2	1	7	8	4
Abnormal, CS, Week 8, n=36, 16, 21, 21, 22, 19	0	0	0	1	0	0
Abnormal, NCS, Week 12, n= 35, 16, 20, 23, 22, 21	9	3	3	8	8	4
Abnormal, CS, Week 12, n=35, 16, 20, 23, 22, 21	0	0	0	0	0	0
Abnormal, NCS, Week 16, n= 35, 16, 21, 21, 22 ,21	9	3	2	5	7	4
Abnormal, CS, Week 16, n=35, 16, 21, 21, 22, 21	0	0	0	0	0	0
Abnormal, NCS, Week 20, n=35, 16, 22, 22, 22, 20	8	3	2	7	8	3
Abnormal, CS, Week 20, n=35, 16, 22, 22, 22, 20	0	0	0	0	0	0

Notes
[97] - Safety Population
[98] - Safety Population
[99] - Safety Population
[100] - Safety Population
[101] - Safety Population
[102] - Safety Population

No statistical analyses for this end point

Secondary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

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End point title

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

End point description

SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[103]	16 ^[104]	22 ^[105]	22 ^[106]	22 ^[107]	21 ^[108]
Units: Millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
SBP	-3.3 ± 13.33	-2.1 ± 11.47	0.1 ± 12.78	0.7 ± 10.42	-0.3 ± 15.16	2.0 ± 15.43
DBP	-1.3 ± 8.99	0.3 ± 7.75	-0.3 ± 9.16	-0.7 ± 5.51	2.5 ± 8.64	2.3 ± 7.23

Notes
[103] - Safety Population
[104] - Safety Population
[105] - Safety Population
[106] - Safety Population
[107] - Safety Population
[108] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in Pulse Rate

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End point title

Change from Baseline in Pulse Rate

End point description

Pulse rate was measured in a semi-supine position after 5 minutes of rest. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[109]	16 ^[110]	22 ^[111]	22 ^[112]	22 ^[113]	21 ^[114]
Units: Beats per minute
arithmetic mean (standard deviation)	1.5 ± 7.19	-2.6 ± 10.35	1.2 ± 10.91	-0.2 ± 7.93	3.4 ± 8.92	0.5 ± 8.03

Notes
[109] - Safety Population
[110] - Safety Population
[111] - Safety Population
[112] - Safety Population
[113] - Safety Population
[114] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment

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End point title

Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment

End point description

GSRS was measured for all 5 domains: Average Diarrhea Syndrome Score, Average Indigestion Syndrome Score, Average Constipation Syndrome Score, Average Abdominal Pain Syndrome Score, Average Reflux Syndrome Score. All individual domains are scored on a 7-point Likert scale ranging from 1(not at all) to 7(extremely). Higher score indicate more severe symptoms. The Average Total GSRS score was mean of these 5 domains and ranges from 1 to 7. Higher score indicates worst possible degree of symptoms. The responses summarized at each visit are those given during the week prior to the visit, with exception of Day 1. Baseline is the most recent assessment completed by participant prior to randomization. Change from Baseline was calculated as post-Baseline value minus the Baseline value. Data has been presented for each domain along with the average Total GSRS score. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 20

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	33 ^[115]	16 ^[116]	20 ^[117]	21 ^[118]	22 ^[119]	20 ^[120]
Units: Scores on a scale
arithmetic mean (standard deviation)
Average Diarrhea Syndrome Score	0.22 ± 1.343	0.15 ± 1.587	0.23 ± 1.180	-0.13 ± 0.637	-0.23 ± 1.729	0.22 ± 1.565
Average Indigestion Syndrome Score	-0.01 ± 1.138	0.09 ± 0.865	-0.03 ± 0.811	-0.14 ± 0.820	-0.31 ± 1.046	-0.54 ± 1.007
Average Constipation Syndrome Score	-0.03 ± 1.045	-0.15 ± 0.989	0.32 ± 1.370	-0.02 ± 0.934	-0.32 ± 1.215	-0.37 ± 0.772
Average Abdominal Pain Syndrome Score	-0.05 ± 1.074	0.06 ± 0.712	-0.02 ± 1.000	-0.06 ± 0.629	-0.08 ± 0.885	-0.25 ± 0.904
Average Reflux Syndrome Score	-0.09 ± 1.208	-0.13 ± 0.619	-0.20 ± 1.332	-0.26 ± 0.664	-0.16 ± 0.762	-0.43 ± 0.847
Average Total Score	0.01 ± 0.830	0.02 ± 0.668	0.07 ± 0.802	-0.11 ± 0.433	-0.23 ± 0.690	-0.28 ± 0.695

Notes
[115] - Safety Population
[116] - Safety Population
[117] - Safety Population
[118] - Safety Population
[119] - Safety Population
[120] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with Mean Worst Daily Itch Score of <4 at Week 16

Top of page

End point title

Number of participants with Mean Worst Daily Itch Score of <4 at Week 16

End point description

Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 is presented.

End point type

Secondary

End point timeframe

At Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[121]	16 ^[122]	23 ^[123]	27 ^[124]	23 ^[125]	22 ^[126]
Units: Participants	21	13	14	18	18	14

Notes
[121] - ITT Population
[122] - ITT Population
[123] - ITT Population
[124] - ITT Population
[125] - ITT Population
[126] - ITT Population

Statistical Analysis 1

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

2.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

12.02

Statistical Analysis 2

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

5.02

Statistical Analysis 3

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

10.76

Statistical Analysis 4

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

10.76

Statistical Analysis 5

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

4.13

Secondary: Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline

Top of page

End point title

Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline

End point description

Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.

End point type

Secondary

End point timeframe

Baseline and At Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[127]	16 ^[128]	23 ^[129]	27 ^[130]	23 ^[131]	22 ^[132]
Units: Participants	17	9	15	14	15	14

Notes
[127] - ITT Population
[128] - ITT Population
[129] - ITT Population
[130] - ITT Population
[131] - ITT Population
[132] - ITT Population

Statistical Analysis 1

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

4.47

Statistical Analysis 2

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

3.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

10.65

Statistical Analysis 3

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

5.53

Statistical Analysis 4

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

2.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

6.92

Statistical Analysis 5

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

6.51

Secondary: Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Top of page

End point title

Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

End point description

Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.

End point type

Secondary

End point timeframe

Baseline and At Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[133]	16 ^[134]	23 ^[135]	27 ^[136]	23 ^[137]	22 ^[138]
Units: Participants	14	6	12	9	13	12

Notes
[133] - ITT Population
[134] - ITT Population
[135] - ITT Population
[136] - ITT Population
[137] - ITT Population
[138] - ITT Population

Statistical Analysis 1

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

3.04

Statistical Analysis 2

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

2.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

6.91

Statistical Analysis 3

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

3.08

Statistical Analysis 4

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

6.42

Statistical Analysis 5

Statistical analysis description

Analysis was performed using Logistic regression. No covariates were used.

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

5.99

Secondary: Percentage of responder days with Worst Daily Itch Score of <4

Top of page

End point title

Percentage of responder days with Worst Daily Itch Score of <4

End point description

Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Percentage of responder days with Worst Daily Itch Score of <4 is presented.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[139]	16 ^[140]	23 ^[141]	27 ^[142]	23 ^[143]	22 ^[144]
Units: Percentage of days
least squares mean (confidence interval 95%)	40.32 (28.79 to 51.86)	58.53 (41.23 to 75.83)	51.38 (36.95 to 65.81)	58.76 (45.45 to 72.08)	65.80 (51.37 to 80.23)	53.58 (38.83 to 68.34)

Notes
[139] - ITT Population
[140] - ITT Population
[141] - ITT Population
[142] - ITT Population
[143] - ITT Population
[144] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

18.21

Confidence interval

level

95%

sides

2-sided

lower limit

-2.59

upper limit

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

11.05

Confidence interval

level

95%

sides

2-sided

lower limit

-7.42

upper limit

29.53

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

18.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

36.06

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

25.48

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

43.95

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.26

Confidence interval

level

95%

sides

2-sided

lower limit

-5.47

upper limit

31.99

Secondary: Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline

Top of page

End point title

Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline

End point description

Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[145]	16 ^[146]	23 ^[147]	27 ^[148]	23 ^[149]	22 ^[150]
Units: Percentage of days
least squares mean (confidence interval 95%)	38.46 (27.30 to 49.61)	53.44 (36.71 to 70.18)	45.43 (31.47 to 59.39)	50.23 (37.35 to 63.12)	60.29 (46.33 to 74.25)	60.03 (45.76 to 74.31)

Notes
[145] - ITT Population
[146] - ITT Population
[147] - ITT Population
[148] - ITT Population
[149] - ITT Population
[150] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

14.99

Confidence interval

level

95%

sides

2-sided

lower limit

-5.13

upper limit

35.1

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

6.97

Confidence interval

level

95%

sides

2-sided

lower limit

-10.9

upper limit

24.84

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

11.78

Confidence interval

level

95%

sides

2-sided

lower limit

-5.27

upper limit

28.82

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

21.83

Confidence interval

level

95%

sides

2-sided

lower limit

3.96

upper limit

39.7

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

21.58

Confidence interval

level

95%

sides

2-sided

lower limit

3.46

upper limit

39.69

Secondary: Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Top of page

End point title

Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

End point description

Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[151]	16 ^[152]	23 ^[153]	27 ^[154]	23 ^[155]	22 ^[156]
Units: Percentage of days
least squares mean (confidence interval 95%)	31.56 (19.96 to 43.16)	37.71 (20.31 to 55.11)	38.82 (24.31 to 53.33)	40.69 (27.29 to 54.08)	51.49 (36.98 to 66.00)	58.60 (43.76 to 73.43)

Notes
[151] - ITT Population
[152] - ITT Population
[153] - ITT Population
[154] - ITT Population
[155] - ITT Population
[156] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

6.15

Confidence interval

level

95%

sides

2-sided

lower limit

-14.76

upper limit

27.06

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

7.26

Confidence interval

level

95%

sides

2-sided

lower limit

-11.32

upper limit

25.84

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

9.13

Confidence interval

level

95%

sides

2-sided

lower limit

-8.59

upper limit

26.85

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

19.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.36

upper limit

38.51

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

27.04

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

45.87

Secondary: Change from Baseline in the Mean Daily Sleep Score at Week 16

Top of page

End point title

Change from Baseline in the Mean Daily Sleep Score at Week 16

End point description

Mean Daily Sleep Score is defined as the average of the daily sleep scores provided in the 7 days prior to the relevant visit. Participants sleep quality was recorded in an electronic diary each morning using a 0-10 NRS in which 0: good sleep to 10:worst possible sleep. Higher score indicates worse possible sleep. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[157]	16 ^[158]	20 ^[159]	22 ^[160]	22 ^[161]	20 ^[162]
Units: Scores on a scale
least squares mean (confidence interval 95%)	-1.39 (-2.06 to -0.72)	-1.66 (-2.64 to -0.67)	-1.87 (-2.75 to -0.99)	-1.85 (-2.69 to -1.01)	-2.35 (-3.19 to -1.50)	-1.69 (-2.57 to -0.81)

Notes
[157] - ITT Population
[158] - ITT Population
[159] - ITT Population
[160] - ITT Population
[161] - ITT Population
[162] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

0.92

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-1.58

upper limit

0.62

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-1.53

upper limit

0.61

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-2.03

upper limit

0.12

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.8

Secondary: Change from Baseline in the Mean Daily Fatigue Score at Week 16

Top of page

End point title

Change from Baseline in the Mean Daily Fatigue Score at Week 16

End point description

Mean Daily Fatigue Score is defined as the average of the daily fatigue scores provided in the 7 days prior to the relevant visit. Participants fatigue level was recorded in an electronic diary each evening using a 0-10 NRS in which 0: no fatigue to 10:worst possible fatigue. Higher score indicates worse possible fatigue. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[163]	16 ^[164]	20 ^[165]	22 ^[166]	22 ^[167]	21 ^[168]
Units: Scores on a scale
least squares mean (confidence interval 95%)	-0.79 (-1.39 to -0.18)	-1.18 (-2.08 to -0.27)	-1.19 (-2.00 to -0.37)	-1.04 (-1.81 to -0.28)	-1.20 (-1.97 to -0.44)	-1.07 (-1.86 to -0.29)

Notes
[163] - ITT Population
[164] - ITT Population
[165] - ITT Population
[166] - ITT Population
[167] - ITT Population
[168] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-1.49

upper limit

0.71

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.41

upper limit

0.61

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

0.72

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

0.56

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

0.7

Secondary: Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16

Top of page

End point title

Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16

End point description

The 5-D itch scale is instrument for multidimensional quantification of itch that is sensitive to change over time. It has data to support its validity in pruritus participants and covers five dimensions of itch: duration, degree, direction, disability and distribution. Each domain was scored on a 5-point scale, ranging from 1 (Not present/resolved/never) to 5 (unbearable/getting worse/always), higher scores indicates worst itching. The scores of each of five domains were achieved separately and then summed together to obtain a total 5-D score. A total 5-D scores ranged between 5 (no pruritus) and 25 (most severe pruritus) where higher score indicates worse possible itching. Baseline is assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[169]	16 ^[170]	21 ^[171]	21 ^[172]	22 ^[173]	20 ^[174]
Units: Scores on a scale
least squares mean (confidence interval 95%)
Duration	-0.8 (-1.1 to -0.4)	-0.9 (-1.3 to -0.4)	-0.4 (-0.8 to 0.0)	-1.2 (-1.6 to -0.8)	-0.6 (-1.0 to -0.2)	-0.7 (-1.1 to -0.3)
Degree	-0.7 (-1.0 to -0.4)	-0.9 (-1.4 to -0.5)	-0.7 (-1.1 to -0.3)	-0.7 (-1.2 to -0.3)	-0.9 (-1.3 to -0.5)	-0.8 (-1.2 to -0.4)
Direction	-0.7 (-1.1 to -0.3)	-0.7 (-1.3 to -0.1)	-0.7 (-1.2 to -0.2)	-0.9 (-1.4 to -0.4)	-1.1 (-1.6 to -0.6)	-0.7 (-1.2 to -0.2)
Disability	-0.4 (-0.7 to 0.0)	-0.8 (-1.4 to -0.2)	-0.5 (-1.0 to 0.0)	-0.7 (-1.2 to -0.2)	-0.7 (-1.2 to -0.2)	-0.7 (-1.2 to -0.1)
Distribution	-0.4 (-0.7 to -0.1)	-0.7 (-1.2 to -0.2)	-0.7 (-1.1 to -0.3)	-0.9 (-1.3 to -0.5)	-0.7 (-1.2 to -0.3)	-0.6 (-1.0 to -0.2)
5-D Itch Total Score	-3.0 (-4.2 to -1.7)	-4.0 (-5.9 to -2.0)	-3.0 (-4.7 to -1.3)	-4.4 (-6.0 to -2.7)	-3.8 (-5.4 to -2.2)	-3.5 (-5.2 to -1.8)

Notes
[169] - ITT Population
[170] - ITT Population
[171] - ITT Population
[172] - ITT Population
[173] - ITT Population
[174] - ITT Population

Statistical Analysis 1

Statistical analysis description

Duration

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.5

Statistical Analysis 2

Statistical analysis description

Duration

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.9

Statistical Analysis 3

Statistical analysis description

Duration

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.1

Statistical Analysis 4

Statistical analysis description

Duration

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.7

Statistical Analysis 5

Statistical analysis description

Duration

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.6

Statistical Analysis 6

Statistical analysis description

Degree

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.3

Statistical Analysis 7

Statistical analysis description

Degree

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.5

Statistical Analysis 8

Statistical analysis description

Degree

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.5

Statistical Analysis 9

Statistical analysis description

Degree

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.3

Statistical Analysis 10

Statistical analysis description

Degree

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.4

Statistical Analysis 11

Statistical analysis description

Direction

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.7

Statistical Analysis 12

Statistical analysis description

Direction

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.6

Statistical Analysis 13

Statistical analysis description

Direction

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.5

Statistical Analysis 14

Statistical analysis description

Direction

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.2

Statistical Analysis 15

Statistical analysis description

Direction

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.6

Statistical Analysis 16

Statistical analysis description

Disability

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.3

Statistical Analysis 17

Statistical analysis description

Disability

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.5

Statistical Analysis 18

Statistical analysis description

Disability

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.3

Statistical Analysis 19

Statistical analysis description

Disability

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.3

Statistical Analysis 20

Statistical analysis description

Disability

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.3

Statistical Analysis 21

Statistical analysis description

Distribution

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.3

Statistical Analysis 22

Statistical analysis description

Distribution

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.2

Statistical Analysis 23

Statistical analysis description

Distribution

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

Statistical Analysis 24

Statistical analysis description

Distribution

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.2

Statistical Analysis 25

Statistical analysis description

Distribution

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.3

Statistical Analysis 26

Statistical analysis description

5-D Itch Total Score

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

1.3

Statistical Analysis 27

Statistical analysis description

5-D Itch Total Score

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

2.1

Statistical Analysis 28

Statistical analysis description

5-D Itch Total Score

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

0.7

Statistical Analysis 29

Statistical analysis description

5-D Itch Total Score

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

1.2

Statistical Analysis 30

Statistical analysis description

5-D Itch Total Score

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

1.6

Secondary: Mean change from Baseline at Week 16 in serum total bile acid concentration

Top of page

End point title

Mean change from Baseline at Week 16 in serum total bile acid concentration

End point description

Blood samples were collected for evaluating total bile acid concentration as a biomarker of PBC. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[175]	16 ^[176]	20 ^[177]	22 ^[178]	21 ^[179]	21 ^[180]
Units: Micromoles per Liter
arithmetic mean (standard deviation)	-4.274 ± 20.0163	-0.469 ± 6.5466	-3.878 ± 40.1857	-1.114 ± 6.9359	-2.133 ± 8.9308	7.379 ± 38.8282

Notes
[175] - ITT Population
[176] - ITT Population
[177] - ITT Population
[178] - ITT Population
[179] - ITT Population
[180] - ITT Population

No statistical analyses for this end point

Secondary: Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)

Top of page

End point title

Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)

End point description

Blood samples were collected for evaluating C4 concentration as a marker of bile acid synthesis. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 16

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	35 ^[181]	15 ^[182]	21 ^[183]	22 ^[184]	22 ^[185]	20 ^[186]
Units: Micrograms per Liter
arithmetic mean (standard deviation)	4.746 ± 11.5644	10.703 ± 24.6045	11.452 ± 16.6371	29.488 ± 38.7584	58.674 ± 59.4833	40.629 ± 36.2769

Notes
[181] - ITT Population
[182] - ITT Population
[183] - ITT Population
[184] - ITT Population
[185] - ITT Population
[186] - ITT Population

No statistical analyses for this end point

Secondary: Plasma concentration of GSK2330672 after sparse sampling

Top of page

End point title

Plasma concentration of GSK2330672 after sparse sampling ^[187]

End point description

Blood samples were collected for measurement of plasma GSK2330672 concentration at Week 4 (between [B/W] 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose. "99999" indicates standard deviation could not be calculated as >30% of samples were below the limit of quantification. Pharmacokinetic (PK) Population consisted of any randomized participant who had at least one PK sample. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)

Notes
[187] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	16 ^[188]	23 ^[189]	27 ^[190]	23 ^[191]	22 ^[192]
Units: Picograms per milliliter
arithmetic mean (standard deviation)
Week 4, B/W 1 and 3 hours post-dose, n=6, 2,7, 0,4	5.00 ± 99999	5.00 ± 99999	32.71 ± 73.325	99999 ± 99999	5.00 ± 99999
Week8, B/W 1 and 3 hour post-dose,n=16,21,20,22,17	358.04 ± 665.685	958.81 ± 1563.265	2327.58 ± 3737.965	453.45 ± 967.424	2908.06 ± 5106.895
Week8, B/W 5 and 8hour post-dose,n=14, 17,18,21,16	300.04 ± 356.268	820.87 ± 1143.023	2234.28 ± 3420.442	339.74 ± 357.914	1990.89 ± 4061.978
Week12,B/W 1 and 3 hours post-dose,n=14,1917,20,14	447.88 ± 1160.518	1594.16 ± 3133.370	2060.51 ± 2888.033	419.47 ± 774.321	3531.36 ± 6296.828
Week12,B/W 5 and 8 hour post-dose,n=14,16,17,20,13	341.39 ± 638.359	1084.00 ± 1353.089	2569.00 ± 3727.883	303.83 ± 300.716	2197.16 ± 3604.704
Week16,B/W 1 and 3hours post-dose,n=3, 5, 4, 2, 5	394.00 ± 162.151	864.26 ± 1045.467	3328.50 ± 3185.646	338.50 ± 236.881	703.60 ± 756.010
Week16,B/W 5 and 8 hour post-dose,n=3, 3, 4, 2, 5	296.33 ± 118.154	578.00 ± 651.263	1940.50 ± 1128.203	364.50 ± 217.082	869.40 ± 1148.331

Notes
[188] - PK Population
[189] - PK Population
[190] - PK Population
[191] - PK Population. 99999 indicates data was not available.
[192] - PK Population. 99999 indicates data was not available.

No statistical analyses for this end point

Post-hoc: Mean change from Baseline in Monthly Itch Score

Top of page

End point title

Mean change from Baseline in Monthly Itch Score

End point description

Participants were required to score severity of their itching each morning and evening using a 0-10 NRS where 0(no itching) and 10(worst imaginable itching). The worst of these 2 scores was Worst Daily Itch Score. For each week, mean Worst Daily Itch Score was calculated to form Mean Worst Daily Itch Score. The Monthly Itch Score was defined as worst weekly score (e.g., Mean Worst Daily Itch Score) for that month. The monthly itch score ranges from 0 to 10, higher score indicates worst imaginable itching. Baseline is average of scores in the 7 days prior to Week 4 (Visit 3 [V3]). Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed on change in Monthly Itch Scores over 12 week treatment period using Mixed model repeated measures (MMRM) with Baseline itch, treatment group, visit and a treatment group*visit interaction as covariates in the model. Only those participants with data available at the specified data points were analyzed.

End point type

Post-hoc

End point timeframe

Baseline and up to Week 12

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[193]	16 ^[194]	23 ^[195]	24 ^[196]	22 ^[197]	22 ^[198]
Units: Scores on a scale
least squares mean (confidence interval 95%)	-0.46 (-1.01 to 0.08)	-1.17 (-1.99 to -0.35)	-1.08 (-1.77 to -0.39)	-1.36 (-2.03 to -0.69)	-1.63 (-2.32 to -0.93)	-1.41 (-2.13 to -0.7)

Notes
[193] - ITT Population
[194] - ITT Population
[195] - ITT Population
[196] - ITT Population
[197] - ITT Population
[198] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.69

upper limit

0.28

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-1.49

upper limit

0.26

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.76

upper limit

-0.03

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.05

upper limit

-0.28

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.95

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

-0.06

Post-hoc: Ratio to Baseline in Total Serum Bile Acid Concentration

Top of page

End point title

Ratio to Baseline in Total Serum Bile Acid Concentration

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Ratio to Baseline was defined as the geometric mean of post-Baseline visit value divided by the geometric mean of Baseline value. Values were log-transformed and mean change from Baseline on the log-scale was calculated over the 12 week treatment period. Analysis was performed on change in total serum bile acid concentration on the log-scale over the 12 week treatment period using MMRM with log-transformed Baseline total serum bile acid, visit, treatment group, a log-transformed Baseline total serum bile acid*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were back-transformed to the original scale. Ratios of geometric means are presented. Only those participants with data available at the specified data points were analyzed.

End point type

Post-hoc

End point timeframe

Baseline and up to Week 12

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[199]	16 ^[200]	22 ^[201]	24 ^[202]	22 ^[203]	22 ^[204]
Units: Ratio
least squares mean (confidence interval 95%)	1.01 (0.801 to 1.273)	0.977 (0.688 to 1.386)	1.182 (0.874 to 1.6)	0.918 (0.687 to 1.226)	0.697 (0.519 to 0.938)	0.833 (0.616 to 1.127)

Notes
[199] - ITT Population
[200] - ITT Population
[201] - ITT Population
[202] - ITT Population
[203] - ITT Population
[204] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

Least Square (LS) mean ratio

Point estimate

0.967

Confidence interval

level

95%

sides

2-sided

lower limit

0.635

upper limit

1.471

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.712

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

0.909

Confidence interval

level

95%

sides

2-sided

lower limit

0.627

upper limit

1.316

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.474

upper limit

1.005

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

0.825

Confidence interval

level

95%

sides

2-sided

lower limit

0.564

upper limit

1.207

Post-hoc: Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration

Top of page

End point title

Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration

End point description

Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Ratio to Baseline was defined as the geometric mean of post-Baseline visit value divided by the geometric mean of Baseline value. Values were log-transformed and mean change from Baseline on the log-scale was calculated over the 12 week treatment period. Analysis was performed on change in C4 on the log-scale over the 12 week treatment period using Mixed model repeated measures (MMRM) with log-transformed Baseline C4, visit, treatment group, a log-transformed Baseline C4*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were back-transformed to the original scale. Ratios of geometric means are presented. Only those participants with data available at the specified data points were analyzed.

End point type

Post-hoc

End point timeframe

Baseline and up to Week 12

End point values	Placebo	GSK2330672 20 mg QD	GSK2330672 90 mg QD	GSK2330672 180 mg QD	GSK2330672 40 mg BID	GSK2330672 90 mg BID
Number of subjects analysed	36 ^[205]	16 ^[206]	22 ^[207]	24 ^[208]	22 ^[209]	22 ^[210]
Units: Ratio
least squares mean (confidence interval 95%)	1.158 (0.937 to 1.431)	1.579 (1.151 to 2.166)	2.374 (1.812 to 3.109)	2.846 (2.192 to 3.694)	3.622 (2.753 to 4.764)	3.127 (2.385 to 4.101)

Notes
[205] - ITT Population
[206] - ITT Population
[207] - ITT Population
[208] - ITT Population
[209] - ITT Population
[210] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2330672 20 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

1.363

Confidence interval

level

95%

sides

2-sided

lower limit

0.932

upper limit

1.995

Statistical Analysis 2

Comparison groups

Placebo v GSK2330672 90 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

2.05

Confidence interval

level

95%

sides

2-sided

lower limit

1.456

upper limit

2.887

Statistical Analysis 3

Comparison groups

Placebo v GSK2330672 180 mg QD

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

2.457

Confidence interval

level

95%

sides

2-sided

lower limit

1.758

upper limit

3.436

Statistical Analysis 4

Comparison groups

Placebo v GSK2330672 40 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

3.128

Confidence interval

level

95%

sides

2-sided

lower limit

2.206

upper limit

4.435

Statistical Analysis 5

Comparison groups

Placebo v GSK2330672 90 mg BID

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

other

Method

Parameter type

LS mean ratio

Point estimate

2.701

Confidence interval

level

95%

sides

2-sided

lower limit

1.915

upper limit

3.81

Adverse events

Top of page

Timeframe for reporting adverse events

Non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to 12 weeks during Main study period; up to 4 weeks during Final study period and up to 4 weeks during Follow-up period.

Adverse event reporting additional description

Safety Population consisted of all randomized participants who received at least 1 dose of study intervention.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Placebo - Main Study Period

Reporting group description

Placebo - Main Study Period

Reporting group title

GSK2330672 20 mg QD - Main Study Period

Reporting group description

GSK2330672 20 mg QD - Main Study Period

Reporting group title

GSK2330672 90 mg QD - Main Study Period

Reporting group description

GSK2330672 90 mg QD - Main Study Period

Reporting group title

GSK2330672 180 mg QD - Main Study Period

Reporting group description

GSK2330672 180 mg QD - Main Study Period

Reporting group title

GSK2330672 40 mg BID - Main Study Period

Reporting group description

GSK2330672 40 mg BID - Main Study Period

Reporting group title

GSK2330672 90 mg BID - Main Study Period

Reporting group description

GSK2330672 90 mg BID - Main Study Period

Reporting group title

Placebo - Final Study Period

Reporting group description

Placebo - Final Study Period

Reporting group title

GSK2330672 20 mg QD - Final Study Period

Reporting group description

GSK2330672 20 mg QD - Final Study Period

Reporting group title

GSK2330672 90 mg QD - Final Study Period

Reporting group description

GSK2330672 90 mg QD - Final Study Period

Reporting group title

GSK2330672 180 mg QD - Final Study Period

Reporting group description

GSK2330672 180 mg QD - Final Study Period

Reporting group title

GSK2330672 40 mg BID - Final Study Period

Reporting group description

GSK2330672 40 mg BID - Final Study Period

Reporting group title

GSK2330672 90 mg BID - Final Study Period

Reporting group description

GSK2330672 90 mg BID - Final Study Period

Reporting group title

Placebo - Follow-up

Reporting group description

Placebo - Follow-up

Reporting group title

GSK2330672 20 mg QD - Follow-up

Reporting group description

GSK2330672 20 mg QD - Follow-up

Reporting group title

GSK2330672 90 mg QD - Follow-up

Reporting group description

GSK2330672 90 mg QD - Follow-up

Reporting group title

GSK2330672 180 mg QD - Follow-up

Reporting group description

GSK2330672 180 mg QD - Follow-up

Reporting group title

GSK2330672 40 mg BID - Follow-up

Reporting group description

GSK2330672 40 mg BID - Follow-up

Reporting group title

GSK2330672 90 mg BID - Follow-up

Reporting group description

GSK2330672 90 mg BID - Follow-up

Placebo - Main Study Period

GSK2330672 20 mg QD - Main Study Period

GSK2330672 90 mg QD - Main Study Period

GSK2330672 180 mg QD - Main Study Period

GSK2330672 40 mg BID - Main Study Period

GSK2330672 90 mg BID - Main Study Period

Placebo - Final Study Period

GSK2330672 20 mg QD - Final Study Period

GSK2330672 90 mg QD - Final Study Period

GSK2330672 180 mg QD - Final Study Period

GSK2330672 40 mg BID - Final Study Period

GSK2330672 90 mg BID - Final Study Period

Placebo - Follow-up

GSK2330672 20 mg QD - Follow-up

GSK2330672 90 mg QD - Follow-up

GSK2330672 180 mg QD - Follow-up

GSK2330672 40 mg BID - Follow-up

GSK2330672 90 mg BID - Follow-up

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 36 (0.00%)

0 / 16 (0.00%)

1 / 23 (4.35%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 35 (0.00%)

1 / 16 (6.25%)

0 / 23 (0.00%)

1 / 27 (3.70%)

0 / 22 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Gastrointestinal disorders

Constipation

subjects affected / exposed

0 / 36 (0.00%)

0 / 16 (0.00%)

0 / 23 (0.00%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 23 (0.00%)

1 / 27 (3.70%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis

subjects affected / exposed

0 / 36 (0.00%)

0 / 16 (0.00%)

1 / 23 (4.35%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 23 (0.00%)

0 / 27 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Lower respiratory tract infection

subjects affected / exposed

0 / 36 (0.00%)

0 / 16 (0.00%)

0 / 23 (0.00%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 35 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 35 (0.00%)

1 / 16 (6.25%)

0 / 23 (0.00%)

0 / 27 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Placebo - Main Study Period	GSK2330672 20 mg QD - Main Study Period	GSK2330672 90 mg QD - Main Study Period	GSK2330672 180 mg QD - Main Study Period	GSK2330672 40 mg BID - Main Study Period	GSK2330672 90 mg BID - Main Study Period	Placebo - Final Study Period	GSK2330672 20 mg QD - Final Study Period	GSK2330672 90 mg QD - Final Study Period	GSK2330672 180 mg QD - Final Study Period	GSK2330672 40 mg BID - Final Study Period	GSK2330672 90 mg BID - Final Study Period	Placebo - Follow-up	GSK2330672 20 mg QD - Follow-up	GSK2330672 90 mg QD - Follow-up	GSK2330672 180 mg QD - Follow-up	GSK2330672 40 mg BID - Follow-up	GSK2330672 90 mg BID - Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 36 (47.22%)	11 / 16 (68.75%)	19 / 23 (82.61%)	24 / 27 (88.89%)	16 / 23 (69.57%)	18 / 22 (81.82%)	2 / 35 (5.71%)	6 / 16 (37.50%)	8 / 19 (42.11%)	2 / 19 (10.53%)	2 / 21 (9.52%)	2 / 17 (11.76%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	1 / 23 (4.35%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	2	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 36 (0.00%)	2 / 16 (12.50%)	0 / 23 (0.00%)	1 / 27 (3.70%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	3 / 36 (8.33%)	1 / 16 (6.25%)	2 / 23 (8.70%)	2 / 27 (7.41%)	1 / 23 (4.35%)	1 / 22 (4.55%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	3	1	2	2	1	1	0	0	1	0	0	0	0	0	0	0	0	0
Impaired healing
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	1 / 23 (4.35%)	1 / 27 (3.70%)	1 / 23 (4.35%)	2 / 22 (9.09%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	1	1	1	2	0	0	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Vulvovaginal dryness
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysmenorrhoea
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	1 / 23 (4.35%)	0 / 27 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Sleep disorder
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	2 / 23 (8.70%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Bone fissure
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Humerus fracture
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ligament sprain
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tooth fracture
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	3 / 23 (13.04%)	2 / 27 (7.41%)	1 / 23 (4.35%)	1 / 22 (4.55%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	5	2	1	1	0	0	1	0	0	0	0	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Eye disorders
Cataract
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 36 (0.00%)	2 / 16 (12.50%)	1 / 23 (4.35%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	3 / 36 (8.33%)	3 / 16 (18.75%)	4 / 23 (17.39%)	8 / 27 (29.63%)	2 / 23 (8.70%)	4 / 22 (18.18%)	0 / 35 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	3	3	6	9	2	5	0	1	0	0	0	0	0	0	0	0	0	0
Abdominal pain lower
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	1 / 23 (4.35%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 36 (0.00%)	2 / 16 (12.50%)	0 / 23 (0.00%)	2 / 27 (7.41%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	4	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	4 / 23 (17.39%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	4 / 36 (11.11%)	6 / 16 (37.50%)	15 / 23 (65.22%)	18 / 27 (66.67%)	12 / 23 (52.17%)	15 / 22 (68.18%)	1 / 35 (2.86%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	5	8	20	22	14	15	1	1	0	0	1	0	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 36 (0.00%)	2 / 16 (12.50%)	1 / 23 (4.35%)	0 / 27 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	2 / 27 (7.41%)	0 / 23 (0.00%)	1 / 22 (4.55%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	1 / 27 (3.70%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	1 / 23 (4.35%)	4 / 27 (14.81%)	0 / 23 (0.00%)	2 / 22 (9.09%)	1 / 35 (2.86%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	2	1	4	0	2	1	1	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	3 / 27 (11.11%)	0 / 23 (0.00%)	2 / 22 (9.09%)	0 / 35 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	0	3	0	2	0	2	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	2 / 36 (5.56%)	0 / 16 (0.00%)	2 / 23 (8.70%)	1 / 27 (3.70%)	0 / 23 (0.00%)	2 / 22 (9.09%)	1 / 35 (2.86%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	3	1	0	2	1	1	1	0	1	1	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Rash macular
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Arthritis
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Bone pain
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	2 / 36 (5.56%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	2 / 23 (8.70%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Back pain
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	0 / 23 (0.00%)	1 / 27 (3.70%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	2 / 36 (5.56%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	1 / 36 (2.78%)	1 / 16 (6.25%)	1 / 23 (4.35%)	1 / 27 (3.70%)	0 / 23 (0.00%)	3 / 22 (13.64%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	1	1	1	0	3	0	0	0	0	0	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	2 / 36 (5.56%)	2 / 16 (12.50%)	0 / 23 (0.00%)	0 / 27 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	2	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin bacterial infection
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 36 (5.56%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 36 (0.00%)	2 / 16 (12.50%)	0 / 23 (0.00%)	0 / 27 (0.00%)	1 / 23 (4.35%)	1 / 22 (4.55%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Viral pharyngitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Infectious mononucleosis
subjects affected / exposed	0 / 36 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Metabolism and nutrition disorders
Vitamin A deficiency
subjects affected / exposed	0 / 36 (0.00%)	1 / 16 (6.25%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 35 (0.00%)	0 / 16 (0.00%)	0 / 23 (0.00%)	0 / 27 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Nov 2016

Amendment 1: To clarify requirements for liver safety monitoring and stopping criteria, as well as other administrative changes.

06 Dec 2017

Amendment 2: To increase access to the trial for participants who will more closely reflect the intended treatment population of primary biliary cholangitis (PBC) participants while maintaining safety, to clarify some existing criteria and information, to make administrative changes, and to correct minor typographical and grammatical errors.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score

Primary: Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score

Secondary: Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale

Secondary: Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale

Secondary: Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression

Secondary: Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16

Secondary: Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16

Secondary: Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression

Secondary: Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression

Secondary: Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period

Secondary: Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period

Secondary: Number of participants with non-SAEs and SAEs -Final study period

Secondary: Number of participants with non-SAEs and SAEs -Final study period

Secondary: Number of participants with non-SAEs and SAEs - Follow-up period

Secondary: Number of participants with non-SAEs and SAEs - Follow-up period

Secondary: Number of participants with clinical chemistry data of potential clinical importance

Secondary: Number of participants with clinical chemistry data of potential clinical importance

Secondary: Number of participants with hematology data of potential clinical importance

Secondary: Number of participants with hematology data of potential clinical importance

Secondary: Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters

Secondary: Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters

Secondary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Secondary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Secondary: Change from Baseline in Pulse Rate

Secondary: Change from Baseline in Pulse Rate

Secondary: Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment

Secondary: Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment

Secondary: Number of participants with Mean Worst Daily Itch Score of <4 at Week 16

Secondary: Number of participants with Mean Worst Daily Itch Score of <4 at Week 16

Secondary: Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Percentage of responder days with Worst Daily Itch Score of <4

Secondary: Percentage of responder days with Worst Daily Itch Score of <4

Secondary: Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

Secondary: Change from Baseline in the Mean Daily Sleep Score at Week 16

Secondary: Change from Baseline in the Mean Daily Sleep Score at Week 16

Secondary: Change from Baseline in the Mean Daily Fatigue Score at Week 16

Secondary: Change from Baseline in the Mean Daily Fatigue Score at Week 16

Secondary: Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16

Secondary: Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16

Secondary: Mean change from Baseline at Week 16 in serum total bile acid concentration

Secondary: Mean change from Baseline at Week 16 in serum total bile acid concentration

Secondary: Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)

Secondary: Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)

Secondary: Plasma concentration of GSK2330672 after sparse sampling

Secondary: Plasma concentration of GSK2330672 after sparse sampling

Post-hoc: Mean change from Baseline in Monthly Itch Score

Post-hoc: Mean change from Baseline in Monthly Itch Score

Post-hoc: Ratio to Baseline in Total Serum Bile Acid Concentration

Post-hoc: Ratio to Baseline in Total Serum Bile Acid Concentration

Post-hoc: Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration

Post-hoc: Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration

Adverse events