Effect of PBI-4050 on the Pharmacokinetics of Midazolam in Heathy Adult Subjects

NCT03637049 | Completed Phase 1 FDA Drug

• 2 other identifiers: PBI-4050-CT-9-16CA25590
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of PBI-4050 combined with midazolam in healthy adult subjects.

Conditions

Healthy

Keywords

PBI-4050; drug-drug interaction; CYP3A; midazolam; healthy subjects

Outcome Measures

Primary Outcomes (4)

• Change in area under the concentration-time curve (AUC0-t) for midazolam and 1-OH-midazolam in presence of PBI-4050

  AUC0-t (AUC from time 0 to last observed non-zero concentration) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)

  PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2

• Change in area under the concentration-time curve (AUC0-inf) for midazolam and 1-OH-midazolam in presence of PBI-4050

  AUC0-inf (AUC from time 0 extrapolated to infinity) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)

  PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2

• Change in maximum plasma concentration (Cmax) for midazolam and 1-OH-midazolam in presence of PBI-4050

  Cmax of midazolam and 1-OH-midazolam assessed on Day 1(Period 1) and Day 5 (Period 2)

  PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2

• Change in concentration observed at the end of the dosing interval (Ctrough) for plasma PBI-4050 and its major metabolite

  Ctrough is the concentration observed at the end of the dosing interval in Period 2.

  PK sampling for PBI-4050 and its metabolite done at pre-dose on Days 3, 4, and 5 of Peiod 2

Secondary Outcomes (1)

• Adverse Events (AEs) and Serious Adverse Events (SAEs)

  10 days

Study Arms (1)

PBI-4050 and midazolam

EXPERIMENTAL

Midazolam 2 mg solution once (Period 1), PBI-4050 1200 mg (3 x 400 mg tablets) once per day for 5 days and midazolam 2 mg solution once on last day (Period 2).

Drug: PBI-4050 and midazolam

Interventions

PBI-4050 and midazolam DRUG

A single oral dose of midazolam (1 mL of 2mg/mL syrup) will be given to all subjects in Period 1 and on Day 5 of Period 2. 1200 mg of PBI-4050 (3 X 400 mg tablets) will be administered for 5 days (Day 1 to Day 5) of Period 2 and a single dose of midazolam (1 mL of 2mg/mL) on Day 5.

PBI-4050 and midazolam

Eligibility Criteria

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

You may qualify if:

• Males or females (WONCBP only).
• Age 18-65 years.
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
• Generally good health.
• Males willing to use appropriate contraception.

You may not qualify if:

• Significant medical history or physical findings.
• History or presence of drug allergy or hypersensitivity to treatment ingredients.
• Gastrointestinal surgery.
• Pregnant or lactating.
• Positive urine drug or alcohol screen.
• Abnormal heart rate or blood pressure.
• Prescribed systemic or topical medication taken recently, or supplements/remedies interfering with study procedures or safety.
• Receiving drugs known as significant inducers of CYP2C9, CYP3A4, CYP2C8 and/or CYP1A2 enzymes and/or P-glycoprotein, including St. John's Wort, for 28 days prior to the first dosing and throughout the study.
• Has been on a diet incompatible with the on-study diet.
• Recent blood donation or significant blood loss.
• Recent blood received.
• Participation in another clinical study within 30 days prior to the first.

Sponsors & Collaborators

• Liminal BioSciences Ltd.: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

setogepram; Midazolam

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 17, 2018
• Study Start: July 17, 2018
• Primary Completion: August 9, 2018
• Study Completion: August 22, 2018
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

US (1)