Drug Interaction Assessment of GSK3882347 in Healthy Participants Aged 18 to 65 Years

NCT05760261 | Completed Phase 1

• 1 other identifier: 213252
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine the magnitude and clinical relevance of a potential drug-drug interaction of GSK3882347 with midazolam (MDZ) in healthy participants. This study assesses the effect of GSK3882347 as an inducer of Cytochrome P450 3A4 (CYP3A4) using MDZ, a sensitive substrate of hepatic and intestinal CYP3A4. The study will investigate MDZ pharmacokinetic (PK) effect in two dosing periods: Period 1: A single dose of MDZ Period 2: 14-days of once daily repeat dosing of GSK3882347 followed by single dose of MDZ co-administered with GSK3882347 on Day 15 (14-days has been selected as this duration is required in order to maximize any potential CYP3A4 enzyme induction).

Conditions

Urinary Tract Infections

Keywords

Drug-drug interaction; Cytochrome P450 3A4 (CYP3A4); 1-hydroxymidazolam; Hormonal contraceptive agent

Outcome Measures

Primary Outcomes (28)

• Period 1: Area under the curve from time zero to 24 hours (AUC [0-24]) for plasma concentration of MDZ

  Up to 24 hours

• Period 1: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ

  Up to 24 hours

• Period 2: AUC (0-24) for plasma concentration of MDZ

  Up to 24 hours

• Period 2: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ

  Up to 24 hours

• Period 1: AUC from time zero to last time of quantifiable concentration (AUC [0-tau]) for plasma concentration of MDZ

  Up to Day 2

• Period 1: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: AUC (0-tau) for plasma concentration of MDZ

  Up to Day 15

• Period 2: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ

  Up to Day 15

• Period 1: AUC from time zero extrapolated to infinite time (AUC [0-inf]) for plasma concentration of MDZ

  Up to Day 2

• Period 1: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: AUC (0-inf) for plasma concentration of MDZ

  Up to Day 15

• Period 2: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ

  Up to Day 15

• Period 1: Maximum plasma concentration (Cmax) of MDZ

  Up to Day 2

• Period 1: Cmax of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: Cmax of MDZ

  Up to Day 15

• Period 2: Cmax of 1-hydroxy-MDZ

  Up to Day 15

• Period 1: Time to Cmax (Tmax) of MDZ

  Up to Day 2

• Period 1: Tmax of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: Tmax of MDZ

  Up to Day 15

• Period 2: Tmax of 1-hydroxy-MDZ

  Up to Day 15

• Period 1: Time lag before observation of measurable concentrations (Tlag) of MDZ

  Up to Day 2

• Period 1: Tlag of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: Tlag of MDZ

  Up to Day 15

• Period 2: Tlag of 1-hydroxy-MDZ

  Up to Day 15

• Period 1: Time to half-life (T1/2) of MDZ

  Up to Day 2

• Period 1: T1/2 of 1-hydroxy-MDZ

  Up to Day 2

• Period 2: T1/2 of MDZ

  Up to Day 15

• Period 2: T1/2 of 1-hydroxy-MDZ

  Up to Day 15

Secondary Outcomes (19)

• Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  Up to Day 15

• Number of participants with clinically significant changes in hematology laboratory values

  Up to Day 15

• Number of participants with clinically significant changes in chemistry laboratory values

  Up to Day 15

• Number of participants with clinically significant changes in urinalysis laboratory values

  Up to Day 15

• Number of participants with clinically significant changes in vital sign values

  Up to Day 15

Study Arms (1)

GSK3882347 and MDZ

EXPERIMENTAL

Period 1: Participants will receive MDZ on Day 1. Period 2: Participants will receive 14-days of repeat dosing of GSK3882347 Followed by one dose of MDZ co-administered with GSK3882347 on Day 15.

Drug: Midazolam; Drug: GSK3882347

Interventions

Midazolam DRUG

Midazolam will be administered.

GSK3882347 and MDZ

GSK3882347 DRUG

GSK3882347 will be administered.

GSK3882347 and MDZ

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Body weight at least 50.0 kilogram (kg) (110 pound \[lbs.\]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5 - 32.0 kg per meter square (kg/m\^2) (inclusive).
• Male participants are eligible to participate if they agree to the following during the study intervention Period and for at least 3 days, after the last dose of study intervention:
• Refrain from donating fresh unwashed semen
• Plus, either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
• Must agree to use contraception/barrier.
• 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 lesser than (\<) 1 percent (%).
• A WOCBP must have a negative highly sensitive pregnancy test \[urine or serum\] as required by local regulations) within 24h before the first dose of study intervention.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
• History or presence of significant cardiovascular, respiratory, hepatic, renal, urological, gastrointestinal, metabolic, endocrinological, hematological, immunologic, dermatologic, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data or in the opinion of the investigator places the participants at unacceptable risk or would make adhering to study procedures for the duration of the study difficult. Participants who have had a gastric bypass or a cholecystectomy are excluded from the study.
• Abnormal blood pressure, as determined by the investigator.
• Alanine transferase (ALT) value greater than (\>)1.5 × upper limit of normal (ULN).
• Bilirubin value \>1.5 × ULN (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Location

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 8, 2023
• Study Start: April 11, 2023
• Primary Completion: August 13, 2024
• Study Completion: August 20, 2024
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

GB (1)