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Methadone

Phase 1

Human Immunodeficiency Virus (HIV) Infection | Small molecule | Infectious Disease |Merck & Company, Inc.|Last Updated: Jun 25, 2019

Target and mechanism

Molecular targetOPRM1
Target classAgonist
ModalitySmall molecule
ChEMBLCHEMBL651

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment14

FDA Designations

No designations recorded

Clinical trial landscape

Methadone · 1 trial · 1 indication

Phase 1 1
NCT02715700Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)Human Immunodeficiency Virus (HIV) Infection
COMPLETED14 Analytics
PHASE1COMPLETED
Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)
Human Immunodeficiency Virus (HIV) InfectionUnlock trial analytics

Study Endpoints

Primary Endpoints

Area Under the Concentration-Time Curve From Zero to 24 Hours After Dosing (AUC0-24) of R-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The AUC0-24 of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by liquid chromatographic-tandem mass spectrometric (LC-MS/MS) detection. The lower limit of quantification (LLoQ) was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Plasma Concentration at 24 Hours After Dosing (C24) of R-Methadone
24 hours postdose on Day 1 and Day 6

The C24 of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Maximum Plasma Concentration (Cmax) of R-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Cmax of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Time to Maximum Plasma Concentration (Tmax) of R-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Tmax of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

AUC0-24 of S-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The AUC0-24 of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

C24 of S-Methadone
24 hours postdose on Day 1 and Day 6

The C24 of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Cmax of S-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Cmax of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Tmax of S-Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Tmax of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

AUC0-24 of Total Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The AUC0-24 of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

C24 of Total Methadone
24 hours postdose on Day 1 and Day 6

The C24 of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Cmax of Total Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Cmax of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

Tmax of Total Methadone
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6

The Tmax of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine). Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada). The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection. The LLoQ was 0.0250 ng/mL for each enantiomer. The analytical range was 0.0250 - 15.0 ng/mL.

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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Maintenance Methadone and MK-1439EXPERIMENTALParticipants maintained on a stable methadone regimen (20 to 200 mg once daily) for ≥14 days prior to Day 1 will continue to receive methadone maintenance once per day on Days 1 to 7. From Day 2 to 6, participants will also receive doravirine 100 mg once daily.

Interventions

NameTypeDescription
MethadoneDRUGMethadone 20 to 200 mg (10 mg/mL if oral solution concentrate) oral tablet once per day.
DoravirineDRUGDoravirine 100 mg oral tablet once per day.
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersYes

Inclusion Criteria: * 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 aft...

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Frequently asked questions about Methadone

What is Methadone used for in HIV infection?

Methadone is a small molecule being studied for use in Human Immunodeficiency Virus (HIV) Infection. It is in Phase 1 clinical development as an investigational drug. The study focuses on how methadone interacts with the HIV treatment doravirine in participants who are already maintained on methadone.

Who makes Methadone?

Methadone is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical research on methadone in the context of HIV infection, with the drug currently in Phase 1 development.

What phase is Methadone in?

Methadone is in Phase 1 clinical development for HIV Infection. It is an investigational drug and has not been approved for this use. One Phase 1 clinical trial has been completed, and the drug remains in early-stage clinical research.

What clinical trials is Methadone in?

Methadone has one completed clinical trial, NCT02715700, titled "Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)." This Phase 1 study enrolled 14 participants and was an uncontrolled, open-label trial in healthy volunteers.

Is Methadone FDA approved?

Methadone is not FDA approved for the treatment of HIV Infection. It is an investigational drug in Phase 1 clinical development for this indication. The completed trial was a pharmacokinetic study, and the drug has not yet progressed to later-stage clinical trials for HIV.

What does the Methadone clinical trial evaluate?

The completed clinical trial for Methadone, NCT02715700, evaluated the effects of doravirine on methadone pharmacokinetics in participants maintained on methadone. The study was Phase 1, uncontrolled, and enrolled 14 healthy volunteers aged 18 years and older.