Clinical Trial Results:
A randomized, doubleblind, multidose, placebocontrolled 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 
201600241641 
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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
201000


Additional study identifiers


ISRCTN number 
  
US NCT number 
  
WHO universal trial number (UTN) 
  
Sponsors


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


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


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


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


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
30 Jul 2020


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
15 Apr 2020


Was the trial ended prematurely? 
No


General information about the trial


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 followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


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 
Japan: 38


Country: Number of subjects enrolled 
United States: 20


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 
Poland: 17


Country: Number of subjects enrolled 
Spain: 5


Country: Number of subjects enrolled 
United Kingdom: 25


Worldwide total number of subjects 
147


EEA total number of subjects 
49


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
111


From 65 to 84 years 
36


85 years and over 
0



Recruitment


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 prespecified interim analysis.  
Preassignment


Screening details 
A total of 147 adult participants were randomized in this study.  
Period 1


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  
Arms


Are arms mutually exclusive 
Yes


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
GSK2330672 was available as whitefilm 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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
GSK2330672 was available as whitefilm 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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
GSK2330672 was available as whitefilm 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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
GSK2330672 was available as whitefilm 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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Arm title

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 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo was available as whitefilm coated tablets to be administered orally.


Investigational medicinal product name 
GSK2330672


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
GSK2330672 was available as whitefilm coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.





Baseline characteristics reporting groups


Reporting group title 
Placebo


Reporting group 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.  
Reporting group title 
GSK2330672 20 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 90 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 180 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 40 mg BID


Reporting group 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.  
Reporting group title 
GSK2330672 90 mg BID


Reporting group 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.  



End points reporting groups


Reporting group title 
Placebo


Reporting group 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.  
Reporting group title 
GSK2330672 20 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 90 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 180 mg QD


Reporting group 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.  
Reporting group title 
GSK2330672 40 mg BID


Reporting group 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.  
Reporting group title 
GSK2330672 90 mg BID


Reporting group 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.  
Subject analysis set title 
Placebo Main Study Period


Subject analysis set type 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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 
Subgroup 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  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received GSK2330672 matching placebo in Main study period and Final study period entered in a 4week notreatment followup period.


Subject analysis set title 
GSK2330672 20 mg QD  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4week notreatment followup period.


Subject analysis set title 
GSK2330672 90 mg QD  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4week notreatment followup period.


Subject analysis set title 
GSK2330672 180 mg QD  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4week notreatment followup period.


Subject analysis set title 
GSK2330672 40 mg BID  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4week notreatment followup period.


Subject analysis set title 
GSK2330672 90 mg BID  Followup


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4week notreatment followup period.



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 010 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 postBaseline 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. IntenttoTreat (ITT) Population comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one ontreatment 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.75  
upper limit 
0.82  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.07  
upper limit 
0.31  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.03  
upper limit 
0.28  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.29  
upper limit 
0.03  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.71  
upper limit 
0.65 


End point title 
Mean change from Baseline at Week 16 in Primary Biliary Cholangitis40 (PBC40) scale  
End point description 
PBC40 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 735, Itch (3 questions) with score range 315, Fatigue (11 questions) with score range 1155, Cognitive (6 questions) with score range 630, Emotional (3 questions) with score range 315, and Social (10 questions) with score range 1050. 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 postBaseline 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




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

Statistical analysis title 
Statistical Analysis 1  
Statistical analysis description 
Symptoms


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
2.3  
Statistical analysis title 
Statistical Analysis 2  
Statistical analysis description 
Symptoms


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
2.5  
Statistical analysis title 
Statistical Analysis 3  
Statistical analysis description 
Symptoms


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.1  
upper limit 
0.8  
Statistical analysis title 
Statistical Analysis 4  
Statistical analysis description 
Symptoms


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
2  
Statistical analysis title 
Statistical Analysis 5  
Statistical analysis description 
Symptoms


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
1.9  
Statistical analysis title 
Statistical Analysis 6  
Statistical analysis description 
Itch


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
2.2  
Statistical analysis title 
Statistical Analysis 7  
Statistical analysis description 
Itch


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
1.3  
Statistical analysis title 
Statistical Analysis 8  
Statistical analysis description 
Itch


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
1.2  
Statistical analysis title 
Statistical Analysis 9  
Statistical analysis description 
Itch


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.6  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 10  
Statistical analysis description 
Itch


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
1.3  
Statistical analysis title 
Statistical Analysis 11  
Statistical analysis description 
Fatigue


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.5  
upper limit 
3.2  
Statistical analysis title 
Statistical Analysis 12  
Statistical analysis description 
Fatigue


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Median difference (net)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
4.2  
Statistical analysis title 
Statistical Analysis 13  
Statistical analysis description 
Fatigue


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
3.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
7  
Statistical analysis title 
Statistical Analysis 14  
Statistical analysis description 
Fatigue


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
5.1  
Statistical analysis title 
Statistical Analysis 15  
Statistical analysis description 
Fatigue


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.6  
upper limit 
3.6  
Statistical analysis title 
Statistical Analysis 16  
Statistical analysis description 
Cognitive


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
2.6  
Statistical analysis title 
Statistical Analysis 17  
Statistical analysis description 
Cognitive


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.9  
upper limit 
1.7  
Statistical analysis title 
Statistical Analysis 18  
Statistical analysis description 
Cognitive


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
2.5  
Statistical analysis title 
Statistical Analysis 19  
Statistical analysis description 
Cognitive


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
2.8  
Statistical analysis title 
Statistical Analysis 20  
Statistical analysis description 
Cognitive


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
2.5  
Statistical analysis title 
Statistical Analysis 21  
Statistical analysis description 
Emotional


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.4  
Statistical analysis title 
Statistical Analysis 22  
Statistical analysis description 
Emotional


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.3  
Statistical analysis title 
Statistical Analysis 23  
Statistical analysis description 
Emotional


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
1.1  
Statistical analysis title 
Statistical Analysis 24  
Statistical analysis description 
Emotional


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 25  
Statistical analysis description 
Emotional


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
1.1  
Statistical analysis title 
Statistical Analysis 26  
Statistical analysis description 
Social


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
3  
Statistical analysis title 
Statistical Analysis 27  
Statistical analysis description 
Social


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
3.7  
Statistical analysis title 
Statistical Analysis 28  
Statistical analysis description 
Social


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
2.7  
Statistical analysis title 
Statistical Analysis 29  
Statistical analysis description 
Social


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
2.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.8  
upper limit 
0.1  
Statistical analysis title 
Statistical Analysis 30  
Statistical analysis description 
Social


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
2.4 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
106.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
251.7  
upper limit 
38.2  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
87.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
198.5  
upper limit 
23.8  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
125.6  
upper limit 
126.5  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
78.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
211.5  
upper limit 
54.8  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
30


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
170.7  
upper limit 
110.7 


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




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 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
21.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
58.4  
upper limit 
15.5  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
12.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
41.9  
upper limit 
16.4  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
49.9  
upper limit 
20  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
26.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
63.3  
upper limit 
10.4  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
36.7  
upper limit 
37.1 


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 
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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
20


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
52.73  
upper limit 
12.74  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
24.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
50.8  
upper limit 
1.39  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
22.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
53.39  
upper limit 
8.16  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
31.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
63.44  
upper limit 
0.09  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
5.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
38.33  
upper limit 
26.74 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
106


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
205.1  
upper limit 
6.8  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
65.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
148.5  
upper limit 
17.6  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
42.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
136.5  
upper limit 
50.9  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
65.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
161.2  
upper limit 
29.5  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
54.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
153.6  
upper limit 
45.3 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
6.099


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.929  
upper limit 
0.268  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
2.337


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.962  
upper limit 
2.289  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
2.232


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.679  
upper limit 
3.215  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.492


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.413  
upper limit 
4.43  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
5.236


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.591  
upper limit 
11.063 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
1.6  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
2.1  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
18


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
2.7  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
17


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
2  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
2.9 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
14


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.08  
upper limit 
0.04  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
20


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.09  
upper limit 
0.01  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
15


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.06  
upper limit 
0.05  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.09  
upper limit 
0.02  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
14


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.02 


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 postBaseline 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




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 title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
14


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
0.63  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
20


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.51  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
15


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.34  
upper limit 
0.58  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
16


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.38  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
14


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.41 


End point title 
Number of participants with nonserious adverse events (NonSAEs) 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




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 


End point title 
Number of participants with nonSAEs and SAEs Final 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.


End point type 
Secondary


End point timeframe 
Up to 4 weeks




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 


End point title 
Number of participants with nonSAEs and SAEs  Followup 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.


End point type 
Secondary


End point timeframe 
Up to 4 weeks




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 


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




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 


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




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 


End point title 
Number of participants with abnormal 12Lead Electrocardiogram (ECG) parameters  
End point description 
A 12lead ECG was recorded with the participant in a semisupine position. 12lead 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




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 


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 semisupine 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 postBaseline 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




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 


End point title 
Change from Baseline in Pulse Rate  
End point description 
Pulse rate was measured in a semisupine 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 postBaseline 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




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 


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 7point 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 postBaseline 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




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 


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 010 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




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

Statistical analysis title 
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 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
12.02  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
1.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.48  
upper limit 
5.02  
Statistical analysis title 
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 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
10.76  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
10.76  
Statistical analysis title 
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 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
1.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
4.13 


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 010 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




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

Statistical analysis title 
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 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
4.47  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
3.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
10.65  
Statistical analysis title 
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 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
1.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
5.53  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.74  
upper limit 
6.92  
Statistical analysis title 
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 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
6.51 


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 010 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




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

Statistical analysis title 
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 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.27  
upper limit 
3.04  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
6.91  
Statistical analysis title 
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 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
1.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.35  
upper limit 
3.08  
Statistical analysis title 
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 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
6.42  
Statistical analysis title 
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 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Odds ratio (OR)  
Point estimate 
2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
5.99 


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 61 divided by number of days from Visit 3+1 to Visit 61 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
18.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.59  
upper limit 
39  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
11.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.42  
upper limit 
29.53  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
18.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
36.06  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
25.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7  
upper limit 
43.95  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
13.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.47  
upper limit 
31.99 


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 61 divided by number of days from Visit 3+1 to Visit 61 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
14.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.13  
upper limit 
35.1  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
6.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.9  
upper limit 
24.84  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
11.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.27  
upper limit 
28.82  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
21.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.96  
upper limit 
39.7  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
21.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.46  
upper limit 
39.69 


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 61 divided by number of days from Visit 3+1 to Visit 61 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
6.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.76  
upper limit 
27.06  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
7.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.32  
upper limit 
25.84  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
9.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.59  
upper limit 
26.85  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
19.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.36  
upper limit 
38.51  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
27.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.2  
upper limit 
45.87 


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 010 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 postBaseline 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.46  
upper limit 
0.92  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.58  
upper limit 
0.62  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.46


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.53  
upper limit 
0.61  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.96


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.03  
upper limit 
0.12  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.8 


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 010 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 postBaseline 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




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.49  
upper limit 
0.71  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.41  
upper limit 
0.61  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
0.72  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.39  
upper limit 
0.56  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.28  
upper limit 
0.7 


End point title 
Change from Baseline in the Five Dimensional (5D) Itch Scale at Week 16  
End point description 
The 5D 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 5point 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 5D score. A total 5D 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 postBaseline 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




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

Statistical analysis title 
Statistical Analysis 1  
Statistical analysis description 
Duration


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 2  
Statistical analysis description 
Duration


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.9  
Statistical analysis title 
Statistical Analysis 3  
Statistical analysis description 
Duration


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.1  
Statistical analysis title 
Statistical Analysis 4  
Statistical analysis description 
Duration


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.7  
Statistical analysis title 
Statistical Analysis 5  
Statistical analysis description 
Duration


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.6  
Statistical analysis title 
Statistical Analysis 6  
Statistical analysis description 
Degree


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 7  
Statistical analysis description 
Degree


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 8  
Statistical analysis description 
Degree


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 9  
Statistical analysis description 
Degree


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 10  
Statistical analysis description 
Degree


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Median difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.4  
Statistical analysis title 
Statistical Analysis 11  
Statistical analysis description 
Direction


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.7  
Statistical analysis title 
Statistical Analysis 12  
Statistical analysis description 
Direction


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.6  
Statistical analysis title 
Statistical Analysis 13  
Statistical analysis description 
Direction


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 14  
Statistical analysis description 
Direction


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.2  
Statistical analysis title 
Statistical Analysis 15  
Statistical analysis description 
Direction


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.6  
Statistical analysis title 
Statistical Analysis 16  
Statistical analysis description 
Disability


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 17  
Statistical analysis description 
Disability


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.5  
Statistical analysis title 
Statistical Analysis 18  
Statistical analysis description 
Disability


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 19  
Statistical analysis description 
Disability


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 20  
Statistical analysis description 
Disability


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 21  
Statistical analysis description 
Distribution


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 22  
Statistical analysis description 
Distribution


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Median difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.2  
Statistical analysis title 
Statistical Analysis 23  
Statistical analysis description 
Distribution


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0  
Statistical analysis title 
Statistical Analysis 24  
Statistical analysis description 
Distribution


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.2  
Statistical analysis title 
Statistical Analysis 25  
Statistical analysis description 
Distribution


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.3  
Statistical analysis title 
Statistical Analysis 26  
Statistical analysis description 
5D Itch Total Score


Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
51


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.3  
upper limit 
1.3  
Statistical analysis title 
Statistical Analysis 27  
Statistical analysis description 
5D Itch Total Score


Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
2.1  
Statistical analysis title 
Statistical Analysis 28  
Statistical analysis description 
5D Itch Total Score


Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
56


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.5  
upper limit 
0.7  
Statistical analysis title 
Statistical Analysis 29  
Statistical analysis description 
5D Itch Total Score


Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3  
upper limit 
1.2  
Statistical analysis title 
Statistical Analysis 30  
Statistical analysis description 
5D Itch Total Score


Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
55


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
1.6 


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 postBaseline 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




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 


End point title 
Mean change from Baseline at Week 16 in serum 7alpha hydroxy4cholesten3one (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 postBaseline 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




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 


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 postdose) and At Weeks 8, 12 and 16 (between 1 and 3 hours postdose, and between 5 and 8 hours postdose. "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 postdose) and At Weeks 8, 12 and 16 (between 1 and 3 hours postdose, and between 5 and 8 hours postdose)


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. 



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 


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 010 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 postBaseline 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 
Posthoc


End point timeframe 
Baseline and up to Week 12




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.69  
upper limit 
0.28  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
59


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.49  
upper limit 
0.26  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
60


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.76  
upper limit 
0.03  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
1.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.05  
upper limit 
0.28  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Mean difference (net)  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.85  
upper limit 
0.06 


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 postBaseline visit value divided by the geometric mean of Baseline value. Values were logtransformed and mean change from Baseline on the logscale was calculated over the 12 week treatment period. Analysis was performed on change in total serum bile acid concentration on the logscale over the 12 week treatment period using MMRM with logtransformed Baseline total serum bile acid, visit, treatment group, a logtransformed Baseline total serum bile acid*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were backtransformed 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 
Posthoc


End point timeframe 
Baseline and up to Week 12




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
Least Square (LS) mean ratio  
Point estimate 
0.967


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.635  
upper limit 
1.471  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
1.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.712  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
60


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
0.909


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.627  
upper limit 
1.316  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
0.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.474  
upper limit 
1.005  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
0.825


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.564  
upper limit 
1.207 


End point title 
Ratio to Baseline in serum 7alphahydroxy4cholesten3one (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 postBaseline visit value divided by the geometric mean of Baseline value. Values were logtransformed and mean change from Baseline on the logscale was calculated over the 12 week treatment period. Analysis was performed on change in C4 on the logscale over the 12 week treatment period using Mixed model repeated measures (MMRM) with logtransformed Baseline C4, visit, treatment group, a logtransformed Baseline C4*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were backtransformed 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 
Posthoc


End point timeframe 
Baseline and up to Week 12




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

Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
Placebo v GSK2330672 20 mg QD


Number of subjects included in analysis 
52


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
1.363


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.932  
upper limit 
1.995  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
Placebo v GSK2330672 90 mg QD


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
2.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.456  
upper limit 
2.887  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
Placebo v GSK2330672 180 mg QD


Number of subjects included in analysis 
60


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
2.457


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.758  
upper limit 
3.436  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
Placebo v GSK2330672 40 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
3.128


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.206  
upper limit 
4.435  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
Placebo v GSK2330672 90 mg BID


Number of subjects included in analysis 
58


Analysis specification 
Posthoc


Analysis type 
other  
Method 

Parameter type 
LS mean ratio  
Point estimate 
2.701


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.915  
upper limit 
3.81 


Adverse events information


Timeframe for reporting adverse events 
Nonserious adverse events (NonSAEs) 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 Followup 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 used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
23.0


Reporting groups


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  Followup


Reporting group description 
Placebo  Followup  
Reporting group title 
GSK2330672 20 mg QD  Followup


Reporting group description 
GSK2330672 20 mg QD  Followup  
Reporting group title 
GSK2330672 90 mg QD  Followup


Reporting group description 
GSK2330672 90 mg QD  Followup  
Reporting group title 
GSK2330672 180 mg QD  Followup


Reporting group description 
GSK2330672 180 mg QD  Followup  
Reporting group title 
GSK2330672 40 mg BID  Followup


Reporting group description 
GSK2330672 40 mg BID  Followup  
Reporting group title 
GSK2330672 90 mg BID  Followup


Reporting group description 
GSK2330672 90 mg BID  Followup  
