NCT03234699

Assess the Influence of Cenobamate on the PK of Cytochrome P450 (CYP) Probe Drugs As a Means of Predicting Drug-drug Interactions

The Effect of Multiple Doses of Cenobamate (YKP3089) on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (midazolam, Warfarin, Omeprazole and Bupropion) Administered Orally in an Open-label, One-sequence Study in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: SK Life Science, Inc. · Industry
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments. The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes. The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Cenobamate	12.5 mg q.d.(Days 13-26), 25 mg q.d. (Days 27-40), 50 mg q.d. (Days 41-54), 100 mg q.d. (Days 55-70), 150 mg q.d. (Days 71-84), 200 mg q.d. (Days 85-110)
DRUG	midazolam	2 mg midazolam syrup (Days 7, 69, 105)
DRUG	Warfarin Pill	5 mg (Days 7 and 105)
DRUG	Omeprazole Pill	20 mg (Days 7 and 105)
DRUG	Bupropion Pill	150 mg (Days 1 and 99)

Timeline

• Start date: 2017-02-22
• Primary completion: 2017-07-03
• Completion: 2017-07-31
• First posted: 2017-07-31
• Last updated: 2024-09-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study