Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis

April 8, 2021 updated by: GlaxoSmithKline

A Randomized, Double-blind, Multi-dose, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of GSK2330672 Administration for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis (GLIMMER: GSK2330672 triaL of IBAT Inhibition With Multidose Measurement for Evaluation of Response)

This study is being conducted to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus (itch) in participants with primary biliary cholangitis (PBC). Participants will receive either placebo or one of the 4 dose regimens of GSK2330672 (20 milligram [mg], 90 mg or 180 mg taken once daily or 90 mg twice daily). Participants on GSK2330672 will also receive placebo tablets to maintain blinding. The study has a prospectively defined adaptive design that will utilize interim data to further inform and potentially optimize the doses under investigation. Hence, additional dose regimen may be added during study. The total duration of a participant in the study will be up to 45 days of screening and 24 weeks of study including follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
147

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • GSK Investigational Site
    • Queensland
      • Herston, Queensland, Australia, 4029
        • GSK Investigational Site
    • Victoria
      • Prahran, Victoria, Australia, 3181
        • GSK Investigational Site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • GSK Investigational Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • GSK Investigational Site
      • Edmonton, Alberta, Canada, T6G 2C8
        • GSK Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • GSK Investigational Site
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • GSK Investigational Site
      • Toronto, Ontario, Canada, M5G 2C4
        • GSK Investigational Site
    • Quebec
      • Montréal, Quebec, Canada, H2X 0A9
        • GSK Investigational Site
  • France
      • Clermont-Ferrand, France, 63003
        • GSK Investigational Site
      • Grenoble Cedex 9, France, 38043
        • GSK Investigational Site
      • Lille cedex, France, 59037
        • GSK Investigational Site
      • Paris cedex 12, France, 75571
        • GSK Investigational Site
      • Pessac cedex, France, 33604
        • GSK Investigational Site
  • Germany
      • Hamburg, Germany, 20246
        • GSK Investigational Site
    • Bayern
      • Erlangen, Bayern, Germany, 91054
        • GSK Investigational Site
    • Saarland
      • Homburg, Saarland, Germany, 66421
        • GSK Investigational Site
  • Italy
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • GSK Investigational Site
    • Lombardia
      • Milano, Lombardia, Italy, 20142
        • GSK Investigational Site
      • Monza (MB), Lombardia, Italy, 20900
        • GSK Investigational Site
    • Toscana
      • Firenze, Toscana, Italy, 50134
        • GSK Investigational Site
    • Veneto
      • Padova, Veneto, Italy, 35128
        • GSK Investigational Site
  • Japan
      • Chiba, Japan, 270-1694
        • GSK Investigational Site
      • Fukui, Japan, 918-8503
        • GSK Investigational Site
      • Gunma, Japan, 371-8511
        • GSK Investigational Site
      • Hiroshima, Japan, 730-8619
        • GSK Investigational Site
      • Hokkaido, Japan, 006-8555
        • GSK Investigational Site
      • Kagawa, Japan, 760-8557
        • GSK Investigational Site
      • Kanagawa, Japan, 252-0375
        • GSK Investigational Site
      • Nagasaki, Japan, 856-8562
        • GSK Investigational Site
      • Osaka, Japan, 545-8586
        • GSK Investigational Site
      • Osaka, Japan, 591-8025
        • GSK Investigational Site
      • Tokyo, Japan, 173-8606
        • GSK Investigational Site
      • Tokyo, Japan, 105-8471
        • GSK Investigational Site
      • Tokyo, Japan, 181-8611
        • GSK Investigational Site
  • Poland
      • Czestochowa, Poland, 42-217
        • GSK Investigational Site
      • Katowice, Poland, 40-506
        • GSK Investigational Site
      • Myslowice, Poland, 41-400
        • GSK Investigational Site
      • Warszawa, Poland, 00-332
        • GSK Investigational Site
      • Wroclaw, Poland, 50-349
        • GSK Investigational Site
  • Spain
      • Barcelona, Spain, 08036
        • GSK Investigational Site
      • Madrid, Spain, 28007
        • GSK Investigational Site
      • Madrid, Spain, 28034
        • GSK Investigational Site
      • Sevilla, Spain, 41013
        • GSK Investigational Site
      • Valencia, Spain, 46026
        • GSK Investigational Site
  • United Kingdom
      • Basingstoke, United Kingdom, RG24 9NA
        • GSK Investigational Site
      • Edgbaston, United Kingdom, B15 2GW
        • GSK Investigational Site
      • Glasgow, United Kingdom, G31 2ER
        • GSK Investigational Site
      • Liverpool., United Kingdom, L7 8XP
        • GSK Investigational Site
      • London, United Kingdom, NW3 2QG
        • GSK Investigational Site
      • Manchester, United Kingdom, M13 9WU
        • GSK Investigational Site
      • Middlesbrough, United Kingdom, TS4 3BW
        • GSK Investigational Site
      • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
        • GSK Investigational Site
      • Nottingham, United Kingdom, NG7 2UH
        • GSK Investigational Site
      • Plymouth, United Kingdom, PL6 8DH
        • GSK Investigational Site
      • Sheffield, United Kingdom, S5 7AU
        • GSK Investigational Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • GSK Investigational Site
    • California
      • Sacramento, California, United States, 95817
        • GSK Investigational Site
    • Florida
      • Miami, Florida, United States, 33136
        • GSK Investigational Site
    • Michigan
      • Novi, Michigan, United States, 48377
        • GSK Investigational Site
    • New Jersey
      • Manhasset, New Jersey, United States, 11030
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10032
        • GSK Investigational Site
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18104
        • GSK Investigational Site
    • Texas
      • Dallas, Texas, United States, 75390-8887
        • GSK Investigational Site
    • Washington
      • Seattle, Washington, United States, 981104
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
  • Participants who have proven PBC, as demonstrated by having at least 2 of the following: History of sustained increased ALP levels >ULN first recognized at least 6 months prior to the Screening Visit (Sustained ALP elevations at the time of Screening is not required, recognizing that the ALP may have decreased after institution of ursodeoxycholic acid (UDCA) therapy as described in inclusion number 4). Documented positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and/or nuclear rim positive). Liver biopsy (at any time in the past) consistent with PBC.
  • Participants must rate their itch severity as being >=4 on a 0 to 10 point scale for the majority of time (at least half the days, as recalled by the participant) during the 8 weeks prior to the Screening Visit. Periods of low itch or no itch are acceptable as long as the worst daily itch score is >=4 on the majority of days.
  • Participants who are currently taking UDCA should be on stable doses of UDCA for >8 weeks at time of screening. Participants not taking UDCA due to intolerance may be enrolled 8 weeks after their last dose of UDCA. No changes or discontinuation is permitted until completion of the Main Study Period.
  • Male and/or female: Female participants- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

  • Screening total bilirubin >2x ULN. Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent (%).
  • Screening ALT or AST >6x ULN.
  • Screening eGFR <45 milliliter (mL)/minute/1.73 square meter (m^2) based on the CKD-EPI.
  • History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
  • Presence of actively replicating viral hepatitis due to hepatitis B or C virus (HBV, HCV) infection, and/or confirmed hepatocellular carcinoma or biliary cancer. Other hepatic conditions ( e.g., primary sclerosing cholangitis [PSC], alcoholic liver disease, autoimmune hepatitis, non-alcoholic steatohepatitis [NASH] ) are permitted if PBC is the dominant liver injury in the investigator's opinion.
  • Current diarrhea.
  • Current symptomatic cholelithiasis or inflammatory gall bladder disease. Participants with history of cholecystectomy >=3 months before screening may be eligible for enrolment.
  • Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures.
  • Initiation or increase in dose of colchicine, methotrexate, azathioprine, or systemic corticosteroids in the 2 months prior to screening. If a change in dose in any of these medications is anticipated during the course of the study, the participant should be excluded.
  • Initiation or increase in dose of bezafibrate or fenofibrate at any time during the 3 months prior to screening. Participants may join the study on stable doses of these medications, but no change or discontinuation is permitted until completion of the Main Study Period.
  • Initiation or increase in dose of any of the following in the 8 weeks prior to screening: rifampicin, naltrexone, naloxone, nalfurafine, or sertraline. Participants may join the study on stable or decreased doses of these medications, but no change in dose is permitted until completion of the Main Study Period.
  • Bile acid binding resin use: a participant must discontinue use of cholestyramine, colesevelam, colestipol or colestimide prior to the start of the Initial Study Period (no later than Day-2). Note: these drugs may be administered after completion of the Main Study Period, if clinically indicated.
  • Obeticholic acid use: a participant must discontinue use of obeticholic acid at least 8 weeks prior to the start of the Initial Study Period and may not restart until after the end of the study.
  • Administration of any other Inhibitor of the Human Ileal Bile Acid Transporter (IBAT) in the 3 months prior to screening.
  • Current enrolment or participation within the 8 weeks before start of the Initial Study Period, in any other clinical study involving an investigational study treatment.
  • QT interval corrected for heart rate QTc >480 millisecond (msec).
  • History of sensitivity to the study treatment or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation in the study.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants will receive matching placebo
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Experimental: GSK2330672 20 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Drug: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Experimental: GSK2330672 90 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Drug: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Experimental: GSK2330672 180 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Drug: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Experimental: GSK2330672 40 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Drug: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Experimental: GSK2330672 90 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Drug: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score
Time Frame: Baseline and Week 16
Participants were required to score the severity of their itching using a 0-10 numerical rating scale (NRS) where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the average of the scores in the 7 days prior to the Week 4 (Visit 3 [V3]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was done using Analysis of covariance (ANCOVA) including treatment group and centered Mean Worst Daily Itch score at Baseline.
Baseline and Week 16

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) Scale
Time Frame: Baseline and at Week 16
PBC-40 is a disease-specific health-related quality of life (HRQoL) questionnaire for use in PBC participants. It consists of 40 questions arranged in 6 domains with 3 to 11 questions in each domain. Each question is scored from 1 (least impact) to 5 (greatest impact). All questions within a domain are summed to obtain individual domain score. Domains were: Symptoms (7 questions) with score range 7-35, Itch (3 questions) with score range 3-15, Fatigue (11 questions) with score range 11-55, Cognitive (6 questions) with score range 6-30, Emotional (3 questions) with score range 3-15, and Social (10 questions) with score range 10-50. Higher scores for individual domains represent a poor quality of life. Baseline is the assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Serum Alkaline Phosphatase (ALP) Concentrations, in Participants With High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Criteria for high risk of PBC progression is defined as serum ALP concentrations more than or equal to (>=)1.67 times upper limit of normal (ULN) range and/or total bilirubin concentrations more than (>)ULN at Day 1. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
Baseline and at Week 16
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
Time Frame: At Week 16
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.
At Week 16
Mean Change From Baseline at Week 16 in Serum Alanine Aminotransferase (ALT) Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Serum Aspartate Aminotransferase (AST) Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Serum Gamma Glutamyl Transferase (GGT), Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Total Bilirubin Concentration, Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Albumin Concentration, Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Prothrombin International Normalized Ratio (INR), Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Prothrombin Time, Among Those With a High Risk of PBC Progression
Time Frame: Baseline and at Week 16
Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
Baseline and at Week 16
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) -Main Study Period
Time Frame: Up to 12 weeks
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.
Up to 12 weeks
Number of Participants With Non-SAEs and SAEs -Final Study Period
Time Frame: Up to 4 weeks
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.
Up to 4 weeks
Number of Participants With Non-SAEs and SAEs - Follow-up Period
Time Frame: Up to 4 weeks
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.
Up to 4 weeks
Number of Participants With Clinical Chemistry Data of Potential Clinical Importance
Time Frame: At Weeks 8, 12, 16 and 20
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 "To Low" and/or "To High" categories with potential clinical importance data have been presented.
At Weeks 8, 12, 16 and 20
Number of Participants With Hematology Data of Potential Clinical Importance
Time Frame: At Weeks 8, 12, 16 and 20
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 "To Low" and/or "To High" categories with potential clinical importance data have been presented.
At Weeks 8, 12, 16 and 20
Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Parameters
Time Frame: At Weeks 8, 12, 16 and 20
A 12-lead ECG was recorded with the participant in a semi-supine position. 12-lead ECGs were obtained by using an automated ECG machine. Data for abnormal, not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
At Weeks 8, 12, 16 and 20
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time Frame: Baseline and Week 20
SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Baseline and Week 20
Change From Baseline in Pulse Rate
Time Frame: Baseline and Week 20
Pulse rate was measured in a semi-supine position after 5 minutes of rest. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Baseline and Week 20
Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Assessment
Time Frame: Baseline and Week 20
GSRS is a validated scale used to assess gastrointestinal symptoms experienced by participants over the preceding 5 to 7 days. GSRS was measured for all 5 domains: Average Diarrhea Syndrome Score, Average Indigestion Syndrome Score, Average Constipation Syndrome Score, Average Abdominal Pain Syndrome Score, Average Reflux Syndrome Score. All individual domains are scored on a 7-point Likert scale ranging from 1(not at all) to 7(extremely). Higher score indicate more severe symptoms. The Average Total GSRS score was mean of these 5 domains and ranges from 1 to 7. Higher score indicates worst possible degree of symptoms. The responses summarized at each visit are those given during the week prior to the visit, with exception of Day 1. Baseline is the most recent assessment completed by participant prior to randomization. Change from Baseline was calculated as post-Baseline value minus the Baseline value. Data has been presented for each domain along with the average Total GSRS score.
Baseline and Week 20
Number of Participants With Mean Worst Daily Itch Score of <4 at Week 16
Time Frame: At Week 16
Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 is presented.
At Week 16
Number of Participants With Improvement of >= 30 Percent (%) in the Mean Worst Daily Itch Score at Week 16 From Baseline
Time Frame: Baseline and At Week 16
Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
Baseline and At Week 16
Number of Participants With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
Time Frame: Baseline and At Week 16
Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
Baseline and At Week 16
Percentage of Responder Days With Worst Daily Itch Score of <4
Time Frame: Up to Week 16
Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Percentage of responder days with Worst Daily Itch Score of <4 is presented.
Up to Week 16
Percentage of Responder Days With Improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 From Baseline
Time Frame: Baseline and at Week 16
Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented..
Baseline and at Week 16
Percentage of Responder Days With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
Time Frame: Baseline and at Week 16
Percentage of Responder Days with Worst Daily Itch was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
Baseline and at Week 16
Change From Baseline in the Mean Daily Sleep Score at Week 16
Time Frame: Baseline and at Week 16
Mean Daily Sleep Score is defined as the average of the daily sleep scores provided in the 7 days prior to the relevant visit. Participants sleep quality was recorded in an electronic diary each morning using a 0-10 NRS in which 0: good sleep to 10:worst possible sleep. Higher score indicates worse possible sleep. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
Baseline and at Week 16
Change From Baseline in the Mean Daily Fatigue Score at Week 16
Time Frame: Baseline and at Week 16
Mean Daily Fatigue Score is defined as the average of the daily fatigue scores provided in the 7 days prior to the relevant visit. Participants fatigue level was recorded in an electronic diary each evening using a 0-10 NRS in which 0: no fatigue to 10:worst possible fatigue. Higher score indicates worse possible fatigue. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
Baseline and at Week 16
Change From Baseline in the Five-Dimensional (5-D) Itch Scale at Week 16
Time Frame: Baseline and at Week 16
The 5-D itch scale had been developed as a brief, single page, instrument for the multidimensional quantification of itch that is sensitive to change over time. It has data to support its validity in a population of participants with pruritus and covers five dimensions of itch experienced by participants: duration, degree, direction, disability and distribution. Each domain was scored on a 5-point scale, ranging from 1 (Not present/resolved/never) to 5 (unbearable/getting worse/always), higher scores indicates worst itching. The scores of each of five domains were achieved separately and then summed together to obtain a total 5-D score. A total 5-D scores potentially ranged between 5 (no pruritus) and 25 (most severe pruritus) where higher score indicates worse possible itching. Baseline is assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Serum Total Bile Acid Concentration
Time Frame: Baseline and at Week 16
Blood samples were collected for evaluating total bile acid concentration as a biomarker of PBC. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Baseline and at Week 16
Mean Change From Baseline at Week 16 in Serum 7-alpha Hydroxy-4-cholesten-3-one (C4)
Time Frame: Baseline and at Week 16
Blood samples were collected for evaluating C4 concentration as a marker of bile acid synthesis. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Baseline and at Week 16
Plasma Concentration of GSK2330672 After Sparse Sampling
Time Frame: At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)
Blood samples were collected for measurement of plasma GSK2330672 concentration.
At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 15, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 15, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 15, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 17, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201000
  • 2016-002416-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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