NCT06118684

Clinical Trial to Assess Effect of Verapamil on Systemic Exposure of EP395 and Effect of EP395 on Systemic Exposure of Midazolam and Digoxin

An Open-label, Healthy Subject, Two-part Study to Assess the Effect of Verapamil on Systemic Exposure of EP395 (Part A), and to Assess the Effect of EP395 on Systemic Exposure of Midazolam and Digoxin (Part B)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: EpiEndo Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The aim of this trial is to assess the potential key drug-drug interactions with EP395 in the clinical setting.

Detailed description

This is an open-label, healthy subject, two-part study to assess the effect of verapamil on systemic exposure of EP395 (Part A), and to assess the effect of EP395 on systemic exposure of midazolam and digoxin (Part B). The overall aim of this trial is to assess the potential key drug-drug interactions (DDIs) with EP395 in the clinical setting. The trial will be in two parts: Part A will investigate EP395 as a 'victim' of DDIs. The impact of CYP3A4 and P-glycoprotein (Pgp) inhibition on the pharmacokinetics (PK) of EP395 will be assessed. Verapamil has been selected as a moderate inhibitor of CYP3A4 and an inhibitor of Pgp. Part B will investigate EP395 as a 'perpetrator' of DDIs. The impact of EP395 on the PK of a CYP3A4 substrate and a Pgp substrate will be assessed. Midazolam has been selected as the CYP3A4 substrate and digoxin as the Pgp substrate. The trial population is healthy adults.

Conditions

• Chronic Obstructive Pulmonary Disease Exacerbation
• COPD

Interventions

Type	Name	Description
DRUG	EP395 (Part A and B)	EP395 (test product) oral capsule 125 mg. Part A: Dose: 1 capsule as a single dose on Day 1 and Day 14, total daily dose: 125 mg. Part B: Dose: 3 capsules once daily on Days 9 to 28, total daily dose: 375 mg.
DRUG	Verapamil (Part A)	Verapamil (CYP3A4/Pgp inhibitor), tablet 40 mg. Part A: Dose: 3 tablets twice daily Days 10 to 18, total daily dose: 240 mg.
DRUG	Midazolam (Part B)	Midazolam (CYP3A4 substrate) oral solution 1 mg/mL. Part B: Dose: 4 mL as a single dose on Day 1 and Day 24, total daily dose: 4 mg.
DRUG	Digoxin (Part B)	Digoxin (Pgp substrate) tablet 0.25 mg. Part B: Dose: 1 tablet as a single dose on Day 1 and Day 24, total daily dose: 0.25 mg.

Timeline

• Start date: 2023-10-23
• Primary completion: 2024-01-02
• Completion: 2024-01-02
• First posted: 2023-11-07
• Last updated: 2024-02-28

Locations

1 site across 1 country: Sweden

Regulatory

• FDA-regulated drug study