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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo
Participants will receive matching placebo
干预措施: Placebo (Drug)
GSK2330672 20 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: Placebo (Drug)
GSK2330672 20 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: GSK2330672 (Drug)
GSK2330672 90 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: Placebo (Drug)
GSK2330672 90 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: GSK2330672 (Drug)
GSK2330672 180 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: Placebo (Drug)
GSK2330672 180 mg once daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: GSK2330672 (Drug)
GSK2330672 40 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: Placebo (Drug)
GSK2330672 40 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: GSK2330672 (Drug)
GSK2330672 90 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: Placebo (Drug)
GSK2330672 90 mg twice daily
Participants will receive GSK2330672 and matching placebo to maintain blind
干预措施: GSK2330672 (Drug)
结局指标
主要结局
Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score
时间窗: 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.
次要结局
- Mean Change From Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) Scale(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(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(At Week 16)
- Mean Change From Baseline at Week 16 in Serum Aspartate Aminotransferase (AST) Among Those With a High Risk of PBC Progression(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(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(Baseline and at Week 16)
- Mean Change From Baseline at Week 16 in Serum Alanine Aminotransferase (ALT) Among Those With a High Risk of PBC Progression(Baseline and at Week 16)
- Mean Change From Baseline at Week 16 in Albumin Concentration, Among Those With a High Risk of PBC Progression(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(Baseline and at Week 16)
- Mean Change From Baseline at Week 16 in Prothrombin Time, Among Those With a High Risk of PBC Progression(Baseline and at Week 16)
- Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) -Main Study Period(Up to 12 weeks)
- Number of Participants With Non-SAEs and SAEs -Final Study Period(Up to 4 weeks)
- Number of Participants With Non-SAEs and SAEs - Follow-up Period(Up to 4 weeks)
- Number of Participants With Clinical Chemistry Data of Potential Clinical Importance(At Weeks 8, 12, 16 and 20)
- Number of Participants With Hematology Data of Potential Clinical Importance(At Weeks 8, 12, 16 and 20)
- Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Parameters(At Weeks 8, 12, 16 and 20)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline and Week 20)
- Change From Baseline in Pulse Rate(Baseline and Week 20)
- Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Assessment(Baseline and Week 20)
- Number of Participants With Mean Worst Daily Itch Score of <4 at Week 16(At Week 16)
- Mean Change From Baseline at Week 16 in Serum Total Bile Acid Concentration(Baseline and at Week 16)
- Mean Change From Baseline at Week 16 in Serum 7-alpha Hydroxy-4-cholesten-3-one (C4)(Baseline and at Week 16)
- Plasma Concentration of GSK2330672 After Sparse Sampling(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))
- Number of Participants With Improvement of >= 30 Percent (%) in the Mean Worst Daily Itch Score at Week 16 From Baseline(Baseline and At Week 16)
- Percentage of Responder Days With Worst Daily Itch Score of <4(Up to Week 16)
- Number of Participants With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline(Baseline and At Week 16)
- Change From Baseline in the Five-Dimensional (5-D) Itch Scale at Week 16(Baseline and at Week 16)
- Percentage of Responder Days With Improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 From Baseline(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(Baseline and at Week 16)
- Change From Baseline in the Mean Daily Sleep Score at Week 16(Baseline and at Week 16)
- Change From Baseline in the Mean Daily Fatigue Score at Week 16(Baseline and at Week 16)