Single Dose IV Methadone for Post-Op Pain

NCT05425420 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: Pro00113821Pro00106216
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Single-center, open label, single-session study to evaluate methadone pharmacokinetics and pharmacodynamic in adults.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetics (PK) in Adults - Systemic Clearance (CL)

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Volume of Distribution

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Elimination Half-life

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Plasma AUC0-96

  Plasma AUC0-96 is the area under the plasma concentration versus time curve from time zero to 96 hours post-dose.

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - AUC0-inf

  AUC0-inf is the area under the curve from time 0 extrapolated to infinite time.

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Cmax

  Cmax: A pharmacokinetic measure used to determine drug dosing. Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Tmax

  Tmax is the time corresponding to maximum concentration post-dose.

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Cmin

  Cmin is the observed minimum concentration post-dose.

  96 hours after dosing

• Pharmacokinetics (PK) in Adults - Elimination Rate Constant

  Elimination rate constant (ke)-s a value used in pharmacokinetics to describe the rate at which a drug is removed from the human system.

  96 hours after dosing

Secondary Outcomes (10)

• Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry

  96 hours after dosing

• Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold

  96 hours after dosing

• Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation

  96 hours after dosing

• Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level

  96 hours after dosing

• Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion

  96 hours after dosing

Study Arms (1)

Single arm, Open label Methadone IV

EXPERIMENTAL

All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight.

Drug: methadone hydrochloride 0.1mg/kg

Interventions

methadone hydrochloride 0.1mg/kg DRUG

Single dose of methadone hydrochloride administered via intravenous (IV)

Single arm, Open label Methadone IV

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to \< 40 years of age at the time of enrollment
• Provide informed consent

You may not qualify if:

• History of cardiac dysfunction
• History of or current QTc prolongation, defined as \> 470 ms in males and \> 480 ms in females
• Known hypersensitivity to methadone hydrochloride or any other ingredient in the methadone hydrochloride injection
• Known acute bronchial asthma or hypercarbia (known history of known PaCO2 above 45 mm HG)
• Receipt of a serotonergic drug or buproprion within 7 days prior to study enrollment
• Receipt of benzodiazepines, muscle relaxants, or other opioids within 7 days prior to study enrollment
• Receipt of a moderate or strong CYP2B6 inhibitor or inducer - either prescription or non-prescription medications, herbals,34 or foods known to be metabolized by or affecting CYP2B6 - within 30 days prior to study enrollment
• CYP2B6 inhibitors include clopidogrel, prasugrel, thioTEPA, ticlopidine, voriconazole, macrolide antibiotics, azole-antifungal agents, fluconazole, Alstonia boonei, Mangifera indica, and Picralima nitida
• CYP2B6 inducers include artemisinin antimalarials, barbiturates, carbamazepine, cyclophosphamide, efavirenz, lopinavir, methimazole, nelfinavir, phenobarbital, phenytoin, primidone, rifampicin/rifampin, ritonavir, abacavir, amprenavir, nevirapine, telaprevir
• Receipt of zidovudine, desipramine, or other drugs that may increase serum concentration when combined with methadone within 30 days prior to study enrollment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Significant respiratory depression (respiratory rate less than 8 breaths/min or oxygen saturation (SpO2) \<95%)
• BMI ≥ 33 and BMI ≤ 17
• Known history of moderate-to-severe liver (Child Class B or C) or kidney disease (serum creatinine \> 1.5)
• Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)

Sponsors & Collaborators

• Kanecia Obie Zimmerman: lead

Study Sites (1)

Duke Early Phase Unit (DEPRU

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Methadone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Results Point of Contact

• Title: Kanecia Zimmerman
• Organization: Duke University

kanecia.zimmerman@duke.edu

919-668-8651

Study Officials

• Kanecia Zimmerman, MD, MPH,PhD

  DUMC, DCRI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: Subjects will be studied on one occasion in the Early Phase Research Unit at Duke University Medical Center for administration of drug, collection of blood samples, and measurements of drug effect. Study drug is intravenous methadone hydrochloride Plasma samples collections are obtained up to 96 hr after dosing. Dark-adapted pupil diameter is measured by infrared camera. Responses to thermal skin stimulation are recorded. Respiratory rate and end-tidal carbon dioxide concentrations are measured. Subject self-assessment of methadone effect is performed using verbal analog scales. Blood samples obtained during the study will be analyzed for plasma concentrations of methadone.

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: June 21, 2022
• Study Start: August 11, 2023
• Primary Completion: January 20, 2024
• Study Completion: January 20, 2024
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)