Single Dose IV Methadone for Post-Op Pain

Pain, Postoperative Clinical Trial

— MTH02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05425420
• Other study ID #: Pro00113821
• Secondary ID: Pro00106216
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 11, 2023
• Est. completion date: January 20, 2024

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 20, 2024
• Est. primary completion date: January 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• methadone hydrochloride 0.1mg/kg
Single dose of methadone hydrochloride administered via intravenous (IV)

Locations

Country	Name	City	State
United States	Duke Early Phase Unit (DEPRU	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Kanecia Obie Zimmerman

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK) in Adults	Systemic clearance	96 hours, after dosing
Primary	Pharmacokinetics (PK) in Adults	Volume of distribution	96 hours, after dosing
Primary	Pharmacokinetics (PK) in Adults	Elimination half-life	96 hours, after dosing
Primary	Pharmacokinetics (PK) in Adults	Plasma AUC0-96 (area under the plasma concentration versus time curve from time zero to 96 hours post-dose).	96 hours, after dosing
Primary	Pharmacokinetics (PK) in Adults	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
Primary	Pharmacokinetics (PK) in Adults	AUC0-8:the area under the curve from time 0 extrapolated to infinite time.	96 hours, after dosing
Primary	Pharmacokinetics (PK) in Adults	Time to maximum concentration (Tmax)	96 hours after dosing
Primary	Pharmacokinetics (PK) in Adults	Minimum concentration (Cmin)	96 hours after dosing
Primary	Pharmacokinetics (PK) in Adults	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	Pharmacodynamics (PD) in Adults	Dark-adapted pupillometry	96 hours, after dosing
Secondary	Pharmacodynamics (PD) in Adults	Thermal Pain tolerance thresholds (highest tolerated temperature change)	96 hours, after dosing
Secondary	Pharmacodynamics (PD) in Adults	Subjective self-assessment of methadone effects using visual analog scale (VAS)	96 hours, after dosing
Secondary	Pharmacodynamics (PD) in Adults	Maximum end-expired CO2 concentration	96 hours, after dosing
Secondary	Pharmacodynamics (PD) in Adults	Maximum sedation score, to obtain the score the Modified Observer's Assessment of Alertness/Sedation, MOAA/S using a 1-5 scale	96 hours, after dosing
Secondary	Pharmacodynamics (PD) in Adults	VAS is a self assessment that indicate levels of alertness/sedation on a scale of 0-100	96 hours, after dosing
Secondary	Characterize the tolerability	Adverse events (AEs)	24 hours of identification/site awareness
Secondary	Serious adverse events (SAEs)	Safety follow-up from baseline to the final visit (96 hours)	24 hours of identification/site awareness
Secondary	Suspected Unexpected Serious Adverse Reactions (SUSARs)	Suspected-Change in QTc, or a SAR that is both serious and unexpected	24 hours of identification/site awareness