Food Effect Study of Linerixibat Tablets in Healthy Adult Participants

NCT05435170 | Completed Phase 1 FDA Drug

• 1 other identifier: 214656
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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

Conditions

Pruritus

Keywords

Pharmacokinetic; Pharmacodynamic; Food effect; Ileal bile acid transporter (IBAT) inhibitor; Linerixibat

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• 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

Study Arms (2)

Treatment sequence AB

EXPERIMENTAL

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

Treatment sequence BA

EXPERIMENTAL

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

Interventions

linerixibat DRUG

linerixibat will be administered per the treatment sequence

Treatment sequence AB; Treatment sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Location

MeSH Terms

Conditions

Pruritus

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinincal Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label study
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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.

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: June 28, 2022
• Study Start: August 11, 2022
• Primary Completion: October 10, 2022
• Study Completion: October 10, 2022
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)