A Phase 2, Double-Blind, Randomized, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Obeticholic Acid Administered in Combination With Bezafibrate in Subjects With Primary Biliary Cholangitis Who Had an Inadequate Response or Who Were Unable to Tolerate Ursodeoxycholic Acid
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 75
- 试验地点
- 62
- 主要终点
- Change in Alkaline Phosphatase (ALP) from baseline to Week 12 in the DB Treatment Period
研究概览
简要总结
Study to evaluate the efficacy, safety, and tolerability of investigational drug obeticholic acid (OCA) in combination with the investigational drug bezafibrate (BZF) in participants with Primary Biliary Cholangitis (PBC).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A definite or probable diagnosis of PBC
- •Qualifying ALP and/or bilirubin liver biochemistry values
- •Taking Ursodeoxycholic Acid (UDCA) for at least 12 months or no UDCA for 3 months before Day 1
排除标准
- •History or presence of other concomitant liver diseases
- •Clinical complications of PBC
- •History or presence of hepatic decompensating events
- •Current or history of gallbladder disease
- •If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
- •Treatment with commercially available OCA or other farnesoid X receptor (FXR) agonists, or participation in a previous study involving OCA within 3 months before Screening.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Treatment A: BZF 200 milligrams (mg) Immediate release (IR)
Participants will receive Bezafibrate (BZF) 200 mg IR + OCA Placebo + BZF 400 mg Placebo
干预措施: Bezafibrate 200 MG (Drug)
Treatment B: BZF 400 mg SR
Participants will receive BZF 400 mg SR + OCA Placebo + BZF 200 mg Placebo
干预措施: Bezafibrate 400 MG (Drug)
Treatment C: OCA 5 mg to 10 mg + BZF 200 mg IR
Participants will receive OCA 5 mg to 10 mg + BZF 200 mg IR + BZF 400 mg Placebo
干预措施: Obeticholic acid (Drug)
Treatment C: OCA 5 mg to 10 mg + BZF 200 mg IR
Participants will receive OCA 5 mg to 10 mg + BZF 200 mg IR + BZF 400 mg Placebo
干预措施: Bezafibrate 200 MG (Drug)
Treatment A: BZF 200 milligrams (mg) Immediate release (IR)
Participants will receive Bezafibrate (BZF) 200 mg IR + OCA Placebo + BZF 400 mg Placebo
干预措施: OCA Placebo (Drug)
Treatment A: BZF 200 milligrams (mg) Immediate release (IR)
Participants will receive Bezafibrate (BZF) 200 mg IR + OCA Placebo + BZF 400 mg Placebo
干预措施: Bezafibrate 400 mg Placebo (Drug)
Treatment D: OCA 5 mg to 10 mg + BZF 400 mg SR
Participants will receive OCA 5 mg to 10 mg + BZF 400 mg SR + BZF 200 mg Placebo
干预措施: Obeticholic acid (Drug)
Treatment D: OCA 5 mg to 10 mg + BZF 400 mg SR
Participants will receive OCA 5 mg to 10 mg + BZF 400 mg SR + BZF 200 mg Placebo
干预措施: Bezafibrate 400 MG (Drug)
Long-term safety extension (LTSE) phase: OCA + BZF
Participants will continue the original treatment assignment allocated during the DB Period. The OCA and BZF dose may be optimized based on safety and efficacy during the DB period.
干预措施: OCA (Drug)
Long-term safety extension (LTSE) phase: OCA + BZF
Participants will continue the original treatment assignment allocated during the DB Period. The OCA and BZF dose may be optimized based on safety and efficacy during the DB period.
干预措施: Bezafibrate (Drug)
Treatment B: BZF 400 mg SR
Participants will receive BZF 400 mg SR + OCA Placebo + BZF 200 mg Placebo
干预措施: OCA Placebo (Drug)
Treatment C: OCA 5 mg to 10 mg + BZF 200 mg IR
Participants will receive OCA 5 mg to 10 mg + BZF 200 mg IR + BZF 400 mg Placebo
干预措施: Bezafibrate 400 mg Placebo (Drug)
Treatment D: OCA 5 mg to 10 mg + BZF 400 mg SR
Participants will receive OCA 5 mg to 10 mg + BZF 400 mg SR + BZF 200 mg Placebo
干预措施: Bezafibrate 200 mg Placebo (Drug)
Treatment B: BZF 400 mg SR
Participants will receive BZF 400 mg SR + OCA Placebo + BZF 200 mg Placebo
干预措施: Bezafibrate 200 mg Placebo (Drug)
结局指标
主要结局
Change in Alkaline Phosphatase (ALP) from baseline to Week 12 in the DB Treatment Period
时间窗: Baseline, Day 1, and Weeks 4, 8, and 12
Change in Alkaline Phosphatase (ALP) From Baseline in the Double-Blind Treatment Period
时间窗: Baseline to Week 12
Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP over time will be analyzed using a mixed model for repeated measures (MMRM) to assess treatment group effects across study visits. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from Baseline was calculated as post Baseline value minus Baseline value.
次要结局
- Number of participants with normalization rates of biochemical disease marker Alanine Aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), Aspartate Aminotransferase (AST), total and conjugated bilirubin and lipid panel(Baseline, Day 1, and Weeks 2, 4, 6, 8, and 12)
- Change in ALT from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Change in GGT from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Response rates of ≥10%, ≥20%, ≥30% and ≥40% reduction, and normalization of biochemical disease marker Alkaline Phosphatase (ALP)(Baseline, Day 1, and Weeks 2, 4, 6, 8, and 12)
- Change in AST from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Change in total and conjugated bilirubin from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Change in 7 alpha (α) hydroxy 4 cholesten-3 one (C4) from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Change in lipid panel from baseline to Week 12(Baseline, Day 1, and Weeks 4, 8, and 12)
- Change in bile acid from baseline to Week 12(Baseline, Day 1, and Weeks 4,8, and 12)
- Percentage of Participants With Response Rates of ≥10%, ≥20%, ≥30% and ≥40% Reduction From Baseline in ALP in the Double-Blind Treatment Period(Week 12)
- Normalization Rates of ALP at Week 12 in the Double-Blind Treatment Period(Week 12)
- Normalization Rates of Biochemical Disease Markers in the Double-Blind Treatment Period(Week 12)
- Change From Baseline in GGT, ALT and AST Levels in the Double-Blind Treatment Period(Baseline and at Week 12)
- Change From Baseline in Total and Conjugated Bilirubin in the Double-Blind Treatment Period(Baseline and at Week 12)
- Change From Baseline in Lipid Panel in the Double-Blind Treatment Period(Baseline and at Week 12)
- Change From Baseline in 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4) in the Double-Blind Treatment Period(Baseline and at Week 12)
- Change From Baseline in Bile Acid in the Double-Blind Treatment Period(Baseline and at Week 12)