Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)
- Registration Number
- NCT04950127
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 238
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Participants receiving linerixibat Linerixibat - Participants receiving linerixibat followed by placebo Linerixibat - Participants receiving linerixibat followed by placebo Placebo - Participants receiving placebo Placebo - Participants receiving placebo followed by linerixibat Linerixibat - Participants receiving placebo followed by linerixibat Placebo -
- Primary Outcome Measures
Name Time Method Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS) Baseline and up to 24 weeks Monthly Itch Score will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching.
- Secondary Outcome Measures
Name Time Method Change from Baseline in Weekly Itch Score at Week 2 Baseline and Week 2 Weekly Itch Score will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching.
Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks Baseline and up to 24 weeks Monthly Sleep Score will be assessed using an NRS scale, ranging from 0 to 10, where 0 represents no sleep interference and 10 is complete sleep interference.
Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score at Week 24 Baseline and Week 24 Number of participants achieving a \>=2-point reduction from Baseline in the Monthly Itch Score will be assessed.
Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score at Week 24 Baseline and Week 24 Number of participants achieving a \>=3-point reduction from Baseline in the Monthly Itch Score will be assessed.
Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score at Week 24 Baseline and Week 24 Number of participants as achieving a \>=4-point reduction from Baseline in the Monthly Itch Score will be assessed.
Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks Baseline and up to 24 weeks Participant-reported overall impression of itch severity will be assessed by PGI-S questionnaire using a 5-level response scale, ranging from absent to very severe.
Patient's Global Impression of Change (PGI-C) scores over 24 weeks Up to 24 weeks Participant-reported change in itch severity will be assessed by PGI-C questionnaire using a 7-level response scale, ranging from very much improved to very much worse.
Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24 Baseline and Week 24 PBC-40 questionnaire measure is comprised of 40 questions, each scored on a scale of 1 to 5 (where 1 = least impact, 5 = greatest impact) grouped into six domains.
Change from Baseline in alkaline phosphatase (ALP) at Week 24 Baseline and Week 24 Change from Baseline in ALP at Week 24 will be evaluated.
Change from Baseline in bilirubin at Week 24 Baseline and Week 24 Change from Baseline in bilirubin at Week 24 will be evaluated.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Surrey, United Kingdom