Food Effect Study of Linerixibat Tablets in Healthy Adult Participants

Pruritus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05435170
• Other study ID #: 214656
• Status: Completed
• Phase: Phase 1
• Start date: August 11, 2022
• Est. completion date: October 10, 2022

Study information

• Verified date: November 2022
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 10, 2022
• Est. primary completion date: October 10, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pruritus

Intervention

Drug:
• linerixibat
linerixibat will be administered per the treatment sequence

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum observed plasma concentration (Cmax) of linerixibat		Up to 36 hours post dose
Secondary	Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to infinite time [AUC (0-8)]		Up to 36 hours post dose
Secondary	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
Secondary	Time of occurrence of Cmax (Tmax) of linerixibat		Up to 36 hours post dose
Secondary	Delay in achieving Tmax (Tlag) of linerixibat		Up to 36 hours post dose
Secondary	Apparent terminal phase half-life (t1/2) of linerixibat		Up to 36 hours post dose
Secondary	Apparent clearance (CL/F) of linerixibat		Up to 36 hours post dose
Secondary	Apparent terminal phase volume of distribution (Vz/F) of linerixibat		Up to 36 hours post dose
Secondary	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
Secondary	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
Secondary	Incidence of adverse events (AEs) and of serious adverse events (SAEs)		Up to day 52