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

A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of PBI-4050 on the Pharmacokinetics of Midazolam, a Sensitive Cytochrome P450 3A Substrate, in Healthy Adult Subjects

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

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

Exclusion Criteria:

1. Significant medical history or physical findings.

2. History or presence of drug allergy or hypersensitivity to treatment ingredients.

3. Gastrointestinal surgery.

4. Pregnant or lactating.

5. Positive urine drug or alcohol screen.

6. Abnormal heart rate or blood pressure.

7. 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.

8. Has been on a diet incompatible with the on-study diet.

9. Recent blood donation or significant blood loss.

10. Recent blood received.

11. Participation in another clinical study within 30 days prior to the first.