Clinical trial NCT05425420: Single Dose IV Methadone for Post-Op Pain
Official title: Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers (MTH02)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pain, Postoperative
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2022-06-21
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: OTHER

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

Detailed description: The Adult Methadone study will be conducted at a single site, Duke Early Phase Research Unity (DEPRU), to enroll 24 participants. Participants will be treated/monitored overnight with Methadone hydrochloride IV (FDA approved and commercially available), with daily follow-up visits for 1 week total. The study aims to provide information on the disposition and clinical effects of intravenous methadone to update the drug label.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK) in Adults - Systemic Clearance (CL)
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Volume of Distribution
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Elimination Half-life
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Plasma AUC0-96
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - AUC0-inf
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Cmax
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Tmax
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Cmin
timeFrame: 96 hours after dosing
measure: Pharmacokinetics (PK) in Adults - Elimination Rate Constant
timeFrame: 96 hours after dosing
Secondary outcomes:
measure: Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Clumsiness
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Anxiety
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Nausea
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Maximum End-expired CO2 Concentration
timeFrame: 96 hours after dosing
measure: Pharmacodynamics (PD) in Adults - Maximum Sedation Score
timeFrame: 96 hours after dosing
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Early Phase Unit (DEPRU
state: North Carolina
Study officials:
affiliation: DUMC, DCRI
name: Kanecia Zimmerman, MD, MPH,PhD
role: PRINCIPAL_INVESTIGATOR
References: