NCT05789173 · Indiana University
Interaction of CYP2B6 Genotype and Efavirenz With Methadone and Tizanidine PK
What this study is about
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).
View original scientific description
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).
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)
Primary outcome measures
Magnitude of effects of CYP2B6 genotype and multiple doses of efavirenz on the: 1) stereoselective disposition of methadone; and 2) disposition and pharmacodynamics of tizanidine
Time frame: Methadone and tizanidine plasma concentrations (0-72 hours) will be determined before (control) and after pretreatment with efavirenz (600 mg/day) for 16 days and AUC0-∞ will be estimated.
1. The primary PK interaction magnitude with R- and S-methadone will be quantified using the treatment:control \[+efavirenz:-efavirenz (baseline)\] ratios of the area under the time concentration curve to infinity (AUC0-∞) of S- and R-methadone. 2. The primary PK interaction magnitude with tizanidine will be quantified using the treatment:control \[+efavirenz:-efavirenz (baseline)\] ratios of the area under the time concentration curve to infinity (AUC0-∞) of tizanidine.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Subjects will be included in the study if participants:
- are male and female (approximately 1:1) volunteers between the age of 18 and 65 years old
- are judged healthy without any significant medical condition as determined by and decided from a pre-enrollment screening session that include medical history, laboratory tests such as blood and urine tests, vital signs, and an electrical tracing of the heartbeat (electrocardiogram, EKG). The pre-enrollment screening will be done no more than six weeks before the start of the study.
- are able and willing to adhere to the study medication restrictions two weeks before initiating the study and during the conduct of the entire study. These will include refraining from taking any prescriptions medications, over-the-counter medications, and herbal, dietary, and alternative supplements that may interact with the metabolism of those study drugs at least 2 weeks prior to the start of the study and until study completion.
- are nonsmoker or individuals willing to refrain from smoking or use of tobacco or marijuana for at least two weeks prior to and until the completion of the study.
- are willing to commit the time requested for this study.
Exclusion criteria
- Subjects will be excluded from the study if participants:
- are underweight (weigh less than 50 kg or 110 lb.) or overweight \[BMI greater than 32\]. Body mass index is calculated using height and weight to estimate how much body fat subjects have.
- have laboratory results that do not fall in a healthy range
- have an electrical tracing (baseline EKG readings) that are abnormal as decided by the study physician (medical doctor).
- have history of intolerance, allergic reactions (e.g., rash) or other forms of hypersensitivities to any of the study medications (efavirenz, tizanidine or methadone).
- Have a hemoglobin count below the normal range (male \<13.4 gm/dL: and female \<12 gm/dL)
- have a positive pregnancy urine test (if female) obtained just prior to each study.
- are sexually active, who is unable or unwilling to use an appropriate and effective method of birth control (for example barrier methods like diaphragms or condoms) to avoid the possibility of becoming pregnant
- are night shift workers in which case taking efavirenz may interfere with their work.
- have any significant health condition such heart, liver, or kidney disease
- have history or current seizures which may lead to collapse.
- have history or current mental illness (brain) such as feeling sad or unhappy, loss of interest in normal activities, worried or suicidality (thoughts about or an unusual preoccupation with ending own life) or suicide attempts.
- have gastrointestinal (digestive) disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs.
- have history or current psychiatric disorders such as depression, anxiety, or suicidality or suicide attempts that may be exacerbated by participation in the study
- have a history of or current HIV infection or have a lifestyle that places participants at a higher risk for contracting HIV (e.g., drug abuse, excessive alcohol drinking, and having multiple sexual partners).
- take more than 2 alcoholic drinks per day on a regular basis for two weeks prior to the study and unwilling to stop alcoholic drinks during the study
- unwilling or unable to stop taking drugs of abuse, including tobacco products or marijuana, two weeks prior to and during the entire study period
- have a systolic blood pressure lower than 70 mm Hg which may place subjects on high risk for tizanidine induced hypotension
- have participated in a research study involving intensive blood sampling or have donated blood within the past two months.
- are taking prescription medications, over-the-counter medications, herbal or dietary supplements, and alternative medicines that may interfere with the metabolism of the study drugs (e.g., inhibitors or inducers of CYP2B6 or CYP1A2) and are unable or unwilling to stop taking these medications two weeks prior to and during the entire study period.
- are employees or students under supervision of any of the study investigators.
- cannot state a good understanding of this study including risks and requirements
- are unable to follow the rules of this study.
- cannot or unwilling to commit the time requested for this study.
Where
- Indianapolis, Indiana
Collaborators
National Institute of General Medical Sciences (NIGMS)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 29, 2026 · Source of record for eligibility and locations