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RECRUITING
NCT05789173
EARLY_PHASE1

Interaction of CYP2B6 Genotype and Efavirenz With Methadone and Tizanidine PK

Sponsor: Indiana University

View on ClinicalTrials.gov

Summary

The main goal of this clinical study is to test how CYP2B6 genetic variations and efavirenz (cornerstone in HIV-1 therapy) dictate the disposition (PK) of CYP2B6 substrate (methadone) and PK and effect (PD) of CYP1A2 substrate (tizanidine). Specifically, the investigators will test whether efavirenz produces CYP2B6 genotype dependent unanticipated DDIs with CYP2B6 (methadone) and CYP1A2 (tizanidine), leading to lack of efficacy or increased toxicity. Healthy volunteers genotyped for CYP2B6\*6 and \*18 alleles will be grouped in to three genotype predicted phenotype groups: 20 normal metabolizer (NM) (CYP2B6\*1/\*1); 20 intermediate metabolizer (IM) (\*1/\*6, or \*1/\*18); and 20 poor metabolizer (PM) (\*6/\*6, \*6/\*18 or \*18/\*18). Each phenotype group will receive methadone and tizanidine (separated by a washout period) on two occasions: at baseline (control) and after treatment with efavirenz (600 mg/day for 17 days).

Official title: Effect of CYP2B6 Genotype and Efavirenz on the Disposition and Pharmacodynamic of Methadone and Tizanidine in Healthy Volunteers

Key Details

Gender

All

Age Range

18 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

60

Start Date

2023-10-06

Completion Date

2026-04-15

Last Updated

2026-02-12

Healthy Volunteers

Yes

Interventions

DRUG

Methadone and Tizanidine

Each CYP2B6 genotype predicted phenotypes will receive methadone (10 mg) and tizanidine (4 mg) by mouth at baseline (control)

DRUG

Efavirenz, Methadone and Tizanidine

Each CYP2B6 genotype predicted phenotypes will receive methadone (10 mg) and tizanidine (4 mg) by mouth after pretreatment with efavirenz (600 mg PO for 16 days)

Locations (1)

Indiana University School of Medicine

Indianapolis, Indiana, United States