A Study to Evaluate the Effects of Multiple Doses of MK-1439 (Doravirine) on Pharmacokinetics of Methadone in Participants Requiring Methadone Maintenance Therapy (MK-1439-045)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party)
Merck Sharp & Dohme Corp.
First received: March 17, 2016
Last updated: September 1, 2016
Last Verified: August 2016
History of Changes
This study will evaluate the effects of multiple doses of MK-1439 (doravirine) on the pharmacokinetics of methadone in participants requiring methadone maintenance therapy. The primary hypothesis is that the Area Under the Concentration-Time curve to 24 hours (AUC0-24) of (R)-methadone is similar when a maintenance regimen of methadone is administered with or without multiple daily doses of MK-1439.
Human Immunodeficiency Virus (HIV) Infection
Drug : Maintenance Methadone
Drug : MK-1439
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Multiple-Dose Clinical Trial to Study the Effect of MK-1439 (Doravirine) on Methadone Pharmacokinetics|
Further study details as provided by Merck Sharp & Dohme Corp.:
Primary Outcome Measures
- Area Under the Concentration-Time Curve from Time Zero to 24 Hours (AUC0-24) of Methadone [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6 ]
- Concentration at 24-Hours After Dosing (C24) of Methadone [ Time Frame: Predose and 24 hours postdose on Day 1 and Day 6 ]
- Maximum Concentration (Cmax) of Methadone [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6 ]
|Study Start Date:||September 2015|
|Study Completion Date:||August 2016|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Maintenance Methadone and MK-1439
Participants receiving a stable methadone maintenance regimen for at least 2 weeks will receive the same formulation and dose of methadone at the study site from Day 1 through Day 7, and will then continue receiving their maintenance methadone at their usual clinic through the end of the study. Beginning on Day 2, participants will receive once daily MK-1439 tablet co-administered (within 5 minutes) with their methadone, for 5 days.
Methadone 20 - 200 mg (10 mg/mL if oral solution concentrate) oral tablets once daily. Participants will receive their stable maintenance methadone at their usual clinic for at least 2 weeks before Day 1. Beginning on Day 1, participants will receive the same formulation and dose of methadone (after an overnight fast) at the study site. On Day 6, participants will be discharged from the study site and resume their maintenance methadone therapy at their usual clinic.
MK-1439 100 mg oral tablet once daily after an overnight fast from Day 2 to Day 6
Other Name: Doravirine
|Ages Eligible for Study:||18 Years to 65 Years|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- If female with reproductive potential: must demonstrate a serum β-human chorionic gonadotropin (β -hCG) level consistent with the nongravid state and agree to use (and/or have their partner use) two acceptable methods of birth control throughout the trial and until 2 weeks after the last dose of trial drug.
- If postmenopausal female: must be without menses for at least 1 year.
- If surgically sterile female: must have a status of post hysterectomy, oophorectomy or tubal ligation.
- Body Mass Index (BMI) of 18-35 kg/m^2 (inclusive).
- Able to comply with the smoking restrictions, including <=10 cigarettes per day while in the Clinical Research Unit, and no smoking from 2 hours predose to 2 hours postdose on Days 1 and 6.
- Reliably participating in a methadone maintenance program for at least two months prior to Day 1. Required to be on a documented stable dose of methadone for at least 14 days prior to Day 1.
- Agree not to change current maintenance methadone dose of 20-200 mg once daily (unless for safety reasons) from screening until the end of the study. Must agree to observation and documentation of daily methadone dose administration during the period of the study during which they are domiciled.
- Mentally or legally incapacitated, have significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or have a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the trial at the discretion of the investigator.
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the trial at the discretion of the investigator.
- History of cancer (malignancy) - exceptions apply.
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
- Positive for Human Immunodeficiency Virus (HIV).
- Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
- Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit.
- Nursing mother.
- Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to the first dose of the 14 day methadone maintenance phase prior to Day 1, throughout the trial, until the post-trial visit - exceptions apply.
- Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day - exceptions apply.
- Consumes excessive amounts of caffeine, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
- Has a positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines (exceptions apply), or opiates/opioids (apart from methadone as assigned maintenance therapy) on Day 1 that cannot be explained by concomitant medications, unless at the discretion of the principal investigator and the sponsor. Must have a negative Urine Drug Screen prior to randomization, with the exception of tetrahydrocannabinol (THC) and prescription benzodiazepines.
- Clinical Opiate Withdrawal Scale (COWS) score of >=5 prior to randomization.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02715700
Sponsors and CollaboratorsMerck Sharp & Dohme Corp.
|Study Director:||Medical Director||Merck Sharp & Dohme Corp.|
|Responsible Party:||Merck Sharp & Dohme Corp.|
|ClinicalTrials.gov Identifier:||NCT02715700 History of Changes|
|Other Study ID Numbers:||1439-045|
|Study First Received:||March 17, 2016|
|Last Updated:||September 1, 2016|
Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.