Food Effect Study of Linerixibat Tablets in Healthy Adult Participants

Study Overview
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Brief Summary
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This study will evaluate the effect of food on the Pharmacokinetic (PK) and Pharmacodynamic (PD) parameters of linerixibat administered in fed and fasted states in heathy adult participants

Official Title
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A Phase I, Randomized, Open-label, Single Dose, 2 Period, Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of Linerixibat Tablets in Healthy Adult Participants

Conditions
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Pruritus

Intervention / Treatment
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* Drug: linerixibat


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Overtly healthy male or female participants 18 to 55 years of age inclusive, at the time of signing the informed consent. Participants' age greater than (>) 50 years old, must have had at least 3 weeks elapsed after the completion of an approved primary SARS-CoV-2 vaccination course. Body weight >50 kg and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m2) (inclusive). Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP). OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year). Capable of giving signed informed consent. Exclusion Criteria: History of cholecystectomy. Current symptomatic cholelithiasis or inflammatory gall bladder disease. Significant history of or current disorders capable of significantly altering the absorption, metabolism, or elimination of drugs. Current clinically significant diarrhea. History of gastrointestinal surgery with ileal resection or ileal bypass at any time. Any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Administration of any other Ileal Bile Acid Transport (IBAT) inhibitor (including linerixibat) in the 3 months prior to screening. Past or intended use of over the counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GSK Medical Monitor. Current enrollment in a clinical trial or recent participation in a clinical trial and has received an investigational product within the following time period prior to study drug administration: 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer). Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5x upper limit of normal (ULN). Bilirubin >1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody test or hepatitis C Ribonucleic acid (RNA) test at screening or within 3 months prior to first dose of study intervention. Positive human immunodeficiency virus (HIV) antibody test Fridericia's QT correction formula (QTcF) >450 msec on ECG performed at screening. Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study. Regular alcohol consumption within 6 months prior to signing the informed consent. Regular use of tobacco- or nicotine-containing products in the 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be randomized to one of the 2 sequences. In sequence AB, participants will receive linerixibat under fed state (Treatment A) in Period 1, then linerixibat under fasted state (Treatment B) in Period 2. In Sequence BA, the 2 treatments will be reversed. The washout period will be of at least 7 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence AB<br>Participants will receive linerixibat in fed state (Treatment A) in period 1 followed by linerixibat in fasted state (Treatment B) in period 2. The washout period will be of at least 7 days. | Drug: linerixibat<br>* linerixibat will be administered per the treatment sequence<br>|
| Experimental: Treatment sequence BA<br>Participants will receive linerixibat in fasted state (Treatment B) in period 1 followed by linerixibat in fed state (Treatment A) in period 2. The washout period will be of at least 7 days. | Drug: linerixibat<br>* linerixibat will be administered per the treatment sequence<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] |  | Up to 36 hours post dose | 
| Maximum observed plasma concentration (Cmax) of linerixibat |  | Up to 36 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to infinite time [AUC (0-∞)] |  | Up to 36 hours post dose | 
| Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)] |  | Up to 24 hours post dose | 
| Time of occurrence of Cmax (Tmax) of linerixibat |  | Up to 36 hours post dose | 
| Delay in achieving Tmax (Tlag) of linerixibat |  | Up to 36 hours post dose | 
| Apparent terminal phase half-life (t1/2) of linerixibat |  | Up to 36 hours post dose | 
| Apparent clearance (CL/F) of linerixibat |  | Up to 36 hours post dose | 
| Apparent terminal phase volume of distribution (Vz/F) of linerixibat |  | Up to 36 hours post dose | 
| Serum C4 area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] |  | Up to 36 hours post dose | 
| Serum C4 area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)] |  | Up to 24 hours post dose | 
| Incidence of adverse events (AEs) and of serious adverse events (SAEs) |  | Up to day 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetic, Pharmacodynamic, Food effect, Ileal bile acid transporter (IBAT) inhibitor, Linerixibat