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

This is a Phase 1, single-center, open-label, 2-period, fixed sequence study to investigate the effect of multiple doses of PBI-4050 on the PK of midazolam, a cytochrome P450 (CYP) 3A substrate, in healthy adult men and healthy women of non-childbearing potential (WONCBP), and to determine the safety and tolerability of PBI-4050, when co-administered with midazolam.

On Day 1 of Period 1, subjects will receive a single oral dose of midazolam followed by PK sampling of midazolam and its metabolite 1-hydroxymidazolam (1-OH-midazolam). In Period 2, subjects will receive multiple daily doses of PBI-4050 for 5 consecutive days (Day 1 to Day 5) with a single oral dose of midazolam co-administered on Day 5. PK sampling for midazolam and 1-OH-midazolam will be collected for 24 hours following dosing on Day 5. PK sampling for PBI-4050 and its major metabolite will be collected at pre-dose on Days 3, 4, and 5.

There will be a washout period of at least 2 days between midazolam dose in Period 1 and the first PBI-4050 dose in Period 2.

Inclusion criteria

• 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.

Exclusion criteria

• 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.