A Two-part, Randomized, Placebo Controlled, Double Blind, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis (PBC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 238
- 试验地点
- 6
- 主要终点
- Part A: Mean Change From Baseline in Monthly Itch Scores Over 24 Weeks Using Numerical Rating Scale (NRS)
研究概览
简要总结
This is a 2-part study in PBC participants with cholestatic pruritus and will evaluate the efficacy, safety and impact on health-related quality of life of linerixibat compared with placebo.
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)
盲法说明
Participants and investigator will be blinded to the study treatment.
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
- •Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
- •Participants who have documented PBC.
- •Participants who have moderate to severe itch.
排除标准
- •Total bilirubin >2.0 times Upper Limit of Normal (ULN) using the average of two Baseline measures.
- •Screening Alanine Aminotransferase (ALT) > 6 times ULN in a single Baseline measure or ALT > 5 times ULN using the average of two Baseline measures.
- •Screening estimated glomerular filtration rate (eGFR) <30 milliliter per minute per 1.73 square meter (mL/min/1.73m^2).
- •History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
- •Presence of HBsAg positive hepatitis B or hepatitis C (HCV) (anti-HCV and Ribonucleic acid [RNA] detected) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
- •Current clinically significant diarrhea or active inflammatory ileal disease according to Investigator´s clinical judgment.
- •Current symptomatic cholelithiasis or cholecystitis.
- •Current diagnosis of primary skin disorders with itch as a characteristic feature (e.g., atopic dermatitis, psoriasis).
- •Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia.
- •Initiation, discontinuation or change in dose of ursodeoxycholic acid (UDCA), bezafibrate or fenofibrate in the 8 weeks prior to Screening.
- •Use of obeticholic acid: within 8 weeks prior to Screening. (Participants may not initiate or restart during the study).
- •Initiation, discontinuation, or change in dose of any of the following in the 8 weeks prior to Screening: bile acid binding resins, rifampicin, naltrexone, naloxone, nalfurafine, pregabalin, gabapentin, sertraline or other selective serotonin reuptake inhibitor (SSRIs), antihistamines used for the treatment of itching.
- •Administration of any other human ileal bile acid transporter (IBAT) inhibitor in the 12 weeks prior to screening.
- •Any planned procedures intended to treat cholestatic pruritus such as nasobiliary drainage or ultraviolet light therapy from Screening and throughout the study.
- •History of sensitivity or intolerance to the study treatment.
研究组 & 干预措施
Part A: Linerixibat 40 milligrams (mg)
Participants were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) in Part A (up to Week 24).
干预措施: Linerixibat (Drug)
Part A: Placebo
Participants were randomized to receive Placebo orally twice a day (BID) in Part A (up to Week 24).
干预措施: Linerixibat (Drug)
Part B: Placebo in Part A and Linerixibat 40 mg in Part B
Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, switched to receive linerixibat 40 mg tablet orally twice a day (BID) (from Week 24 to Week 32) in Part B.
干预措施: Linerixibat (Drug)
Part B: Linerixibat 40 mg in Part A and Placebo in Part B
Participants who were randomized to receive linerixibat 40 mg tablet orally BID (up to Week 24) in Part A, switched to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.
干预措施: Linerixibat (Drug)
Part B: Linerixibat 40 mg in Part A and Part B
Participants who were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) (up to Week 24) in Part A, continued to receive linerixibat 40 mg twice a day (BID) (from Week 24 to Week 32) in Part B.
干预措施: Linerixibat (Drug)
Part A: Placebo
Participants were randomized to receive Placebo orally twice a day (BID) in Part A (up to Week 24).
干预措施: Placebo (Drug)
Part B: Placebo in Part A and Part B
Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, continued to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.
干预措施: Placebo (Drug)
Part B: Placebo in Part A and Linerixibat 40 mg in Part B
Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, switched to receive linerixibat 40 mg tablet orally twice a day (BID) (from Week 24 to Week 32) in Part B.
干预措施: Placebo (Drug)
Part B: Linerixibat 40 mg in Part A and Placebo in Part B
Participants who were randomized to receive linerixibat 40 mg tablet orally BID (up to Week 24) in Part A, switched to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Mean Change From Baseline in Monthly Itch Scores Over 24 Weeks Using Numerical Rating Scale (NRS)
时间窗: Baseline and up to Week 24
Itch Scores were assessed using a NRS twice daily, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching. The worst daily itch score was defined as the worst of the two scores recorded daily. The weekly itch score was defined as the average of the worst daily itch scores in one week. The monthly itch score was defined as the worst weekly itch score for the month (4 weeks). Higher monthly itch scores indicate worse itching. Baseline is the worst weekly itch score in the 28 days prior to randomization (Day 1). Change from Baseline is defined as the post dose value minus baseline value. Least-squares (LS) means and the corresponding 95% confidence intervals are reported by taking average of LS means of change from baseline in monthly itch scores obtained over 24 weeks using equal weighting for all time points. Analyzed using Mixed Model Repeated Measures (MMRM) method.
次要结局
- Part A: Mean Change From Baseline in Weekly Itch Score at Week 2 Using NRS(Baseline and at Week 2)
- Part A: Mean Change From Baseline in Monthly Sleep Score Over 24 Weeks Using NRS(Baseline up to Week 24)
- Part A: Percentage of Responders Defined as Achieving More Than or Equal to (>=) 2-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Percentage of Responders Achieving >=3-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Percentage of Responders as Achieving a >=4-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Mean Change From Baseline in Primary Biliary Cholangitis-40 (PBC-40) Domain Scores at Week 24(Baseline up to Week 24)
- Part A: Mean Change From Baseline in Patient's Global Impression of Severity (PGI-S) Over 24 Weeks(Baseline and up to Week 24)
- Part A: Patient's Global Impression of Change (PGI-C) Scores Over 24 Weeks(Week 4 up to Week 24)
- Part A: Mean Change From Baseline in Alkaline Phosphatase (ALP) at Week 24(Baseline and Week 24)
- Part A: Mean Change From Baseline in Bilirubin at Week 24(Baseline and Week 24)
- Part A: Percentage of Responders Defined as Achieving More Than or Equal to (>=) 2-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Percentage of Responders Achieving >=3-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Percentage of Responders as Achieving a >=4-point Reduction From Baseline in the Monthly Itch Score at Week 24(At Week 24)
- Part A: Mean Change From Baseline in Primary Biliary Cholangitis-40 (PBC-40) Domain Scores at Week 24(Baseline up to Week 24)
- Part A: Mean Change From Baseline in Patient's Global Impression of Severity (PGI-S) Over 24 Weeks(Baseline and up to Week 24)
- Part A: Patient's Global Impression of Change (PGI-C) Scores Over 24 Weeks(Week 4 up to Week 24)
- Part A: Mean Change From Baseline in Alkaline Phosphatase (ALP) at Week 24(Baseline and Week 24)
- Part A: Mean Change From Baseline in Bilirubin at Week 24(Baseline and Week 24)