Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers (MTH02)

Pro00113821

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

2023-08-11

2024-01-20

2024-01-20

Completed

Early phase I

22

Inclusion Criteria: 1. 18 to \< 40 years of age at the time of enrollment 2. Provide informed consent Exclusion Criteria: 1. History of cardiac dysfunction 2. History of or current QTc prolongation, defined as \> 470 ms in males and \> 480 ms in females 3. Known hypersensitivity to methadone hydrochloride or any other ingredient in the methadone hydrochloride injection 4. Known acute bronchial asthma or hypercarbia (known history of known PaCO2 above 45 mm HG) 5. Receipt of a serotonergic drug or buproprion within 7 days prior to study enrollment 6. Receipt of benzodiazepines, muscle relaxants, or other opioids within 7 days prior to study enrollment 7. 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 1. CYP2B6 inhibitors include clopidogrel, prasugrel, thioTEPA, ticlopidine, voriconazole, macrolide antibiotics, azole-antifungal agents, fluconazole, Alstonia boonei, Mangifera indica, and Picralima nitida 2. CYP2B6 inducers include artemisinin antimalarials, barbiturates, carbamazepine, cyclophosphamide, efavirenz, lopinavir, methimazole, nelfinavir, phenobarbital, phenytoin, primidone, rifampicin/rifampin, ritonavir, abacavir, amprenavir, nevirapine, telaprevir 8. Receipt of zidovudine, desipramine, or other drugs that may increase serum concentration when combined with methadone within 30 days prior to study enrollment 9. Known or suspected gastrointestinal obstruction, including paralytic ileus 10. Significant respiratory depression (respiratory rate less than 8 breaths/min or oxygen saturation (SpO2) \<95%) 11. BMI ≥ 33 and BMI ≤ 17 12. Known history of moderate-to-severe liver (Child Class B or C) or kidney disease (serum creatinine \> 1.5) 13. Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction) 14. Females who are pregnant or nursing

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '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.', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 22, 'type': 'ACTUAL'}}

2024-04-19