Clinical trial NCT05435170: Food Effect Study of Linerixibat Tablets in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pruritus
Keywords: Pharmacokinetic
Pharmacodynamic
Food effect
Ileal bile acid transporter (IBAT) inhibitor
Linerixibat
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-06-28
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)]
timeFrame: Up to 36 hours post dose
measure: Maximum observed plasma concentration (Cmax) of linerixibat
timeFrame: Up to 36 hours post dose
Secondary outcomes:
measure: Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to infinite time [AUC (0-∞)]
timeFrame: Up to 36 hours post dose
measure: Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)]
timeFrame: Up to 24 hours post dose
measure: Time of occurrence of Cmax (Tmax) of linerixibat
timeFrame: Up to 36 hours post dose
measure: Delay in achieving Tmax (Tlag) of linerixibat
timeFrame: Up to 36 hours post dose
measure: Apparent terminal phase half-life (t1/2) of linerixibat
timeFrame: Up to 36 hours post dose
measure: Apparent clearance (CL/F) of linerixibat
timeFrame: Up to 36 hours post dose
measure: Apparent terminal phase volume of distribution (Vz/F) of linerixibat
timeFrame: Up to 36 hours post dose
measure: Serum C4 area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)]
timeFrame: Up to 36 hours post dose
measure: Serum C4 area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)]
timeFrame: Up to 24 hours post dose
measure: Incidence of adverse events (AEs) and of serious adverse events (SAEs)
timeFrame: Up to day 52
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinincal Trials
role: STUDY_DIRECTOR
References: