A Phase 2a, Double-Blind, Randomized, Active Controlled, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Bezafibrate Administered in Combination With Obeticholic Acid in Subjects With Primary Biliary Cholangitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 42
- 主要终点
- Change in Alkaline Phosphatase (ALP) from Baseline to Week 12
研究概览
简要总结
Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) 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
- •Presence of clinical complications of PBC
- •History or presence of 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 participation in a previous study involving OCA, or other farnesoid X receptor (FXR) agonists, or peroxisome proliferator activated receptor (PPAR)-agonists within 3 months before Screening
- •Unable to tolerate BZF or other fibrates, treatment with commercially available fibrates, or participation in a previous study involving fibrate within 3 months before Screening.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet
Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily.
干预措施: Bezafibrate 100 mg (Drug)
Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet
Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily.
干预措施: Obeticholic Acid placebo (Drug)
Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet
Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily.
干预措施: Bezafibrate Placebo (Drug)
Double Blind (DB) Phase Treatment B: BZF 400 mg IR tablet
Each Participant will take one OCA placebo tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Bezafibrate 200 mg (Drug)
Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR
Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily.
干预措施: Bezafibrate 100 mg (Drug)
Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR
Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily.
干预措施: Bezafibrate Placebo (Drug)
Double Blind (DB) Phase Treatment B: BZF 400 mg IR tablet
Each Participant will take one OCA placebo tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Obeticholic Acid placebo (Drug)
Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR
Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily.
干预措施: Obeticholic Acid 5 mg (Drug)
Double Blind (DB) Phase Treatment D: OCA 5 mg + BZF 400 mg IR
Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Bezafibrate 200 mg (Drug)
Long Term Safety Extension (LTSE) Phase Treatment D of the DB phase: OCA 5 mg + BZF 400 mg IR
Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Bezafibrate 200 mg (Drug)
Long Term Safety Extension (LTSE) Phase Treatment D of the DB phase: OCA 5 mg + BZF 400 mg IR
Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Obeticholic Acid 5 mg (Drug)
Double Blind (DB) Phase Treatment D: OCA 5 mg + BZF 400 mg IR
Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.
干预措施: Obeticholic Acid 5 mg (Drug)
结局指标
主要结局
Change in Alkaline Phosphatase (ALP) from Baseline to Week 12
时间窗: Baseline, and at Weeks 2, 4, 6, 8, 10 and 12
Change From Baseline in Alkaline Phosphatase (ALP)
时间窗: Baseline to Week 12
Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP were evaluated using a mixed-effects repeated-measures model (MMRM) to assess the effects of treatment groups over time. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product. Change from Baseline was calculated as post Baseline value minus Baseline value.
次要结局
- Change from Baseline in biochemical disease markers, total & conjugated bilirubin(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline in lipid panel(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline of the plasma value of 7 alpha (α) hydroxy 4 cholesten-3 one (C4)(Baseline and at Weeks 2, 4, 6, 8, 10, and 12)
- Change from Baseline in response rates of ≥10 percent, ≥20 percent, ≥30 percent and ≥40 percent reduction and normalization rates of biochemical disease marker ALP(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline in biochemical disease marker ALT(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline in biochemical disease marker AST(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline of the plasma value of bile acids, in unit of nanograms per milliliter (ng/ml)(Baseline and at Weeks 2, 4, 6, 8, 10, and 12)
- Number of participants with normalization rates of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alanine aminotransferase (AST), total and conjugated bilirubin and lipid panel(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Change from Baseline in biochemical disease marker GGT(Baseline and at Weeks 2, 4, 6, 8, 10 and 12)
- Number of Participants With Clinically Significant Changes From Baseline in Bile Acids(At Week 12)
- Percentage of Participants With Response Rates of ≥10%, ≥20%, ≥30% and ≥40% Reduction From Baseline in ALP(At Week 12)
- Normalization Rates of ALP at Week 12(At Week 12)
- Normalization Rates of Biochemical Disease Markers(At Week 12)
- Change From Baseline in in GGT, ALT and AST Levels(Baseline and At Week 12)
- Change From Baseline in Total and Conjugated Bilirubin(Baseline and At Week 12)
- Change From Baseline in Lipid Panel(Baseline and At Week 12)
- Change From Baseline of the Plasma Value of 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4)(Baseline and At Week 12)