Trial Outcomes & Findings for Single Dose IV Methadone for Post-Op Pain (NCT NCT05425420)

NCT ID: NCT05425420

Last Updated: 2025-02-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: 96 hours after dosing
• Results posted on: 2025-02-10

Participant Flow

Participant milestones

Measure	Open Label Methadone IV All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Overall Study STARTED	22
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Open Label Methadone IV All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Overall Study Physician Decision	1
Overall Study Failure to Meet Continuation Criteria	2

Baseline Characteristics

Single Dose IV Methadone for Post-Op Pain

Baseline characteristics by cohort

Measure	Open Label Methadone IV n=22 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Age, Continuous	29.4 years STANDARD_DEVIATION 5.05 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Systemic Clearance (CL)	6.14 liters/hour Standard Deviation 1.42

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Volume of Distribution	318.95 liters Standard Deviation 42.04

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Elimination Half-life	39.66 hours Standard Deviation 9.95

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

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

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Plasma AUC0-96	1088.9 ng*h/mL Standard Deviation 311.9

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

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

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - AUC0-inf	1363.3 ng*h/mL Standard Deviation 515.7

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

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.

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Cmax	90.92 ng/mL Standard Deviation 38.14

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

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

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Tmax	0.116 hours Standard Deviation 0.095

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

Cmin is the observed minimum concentration post-dose.

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Cmin	4.35 ng/mL Standard Deviation 2.41

PRIMARY outcome

Timeframe: 96 hours after dosing

Population: Participants with samples collected at 96 hours.

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

Outcome measures

Measure	Open Label Methadone IV n=20 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacokinetics (PK) in Adults - Elimination Rate Constant	0.018 h^-1 Standard Deviation 0.004

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Dark-adapted pupillometry measured pupil diameter using a goggle-based, camera-like device. A goggle-based system effectively allowed the participant to be in the dark while room lights were on for research staff.

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry Right pupil	7.57 mm Standard Deviation 1.29
Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry Left pupil	6.95 mm Standard Deviation 1.30

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

The thermal pain tolerance threshold is the highest tolerated temperature change. Thermal pain tolerance was measured by a 3 cm2 computer-controlled Peltier-type thermal stimulator. The stimulator delivered painful heat stimuli to the volar side of the forearm. The thermode system's baseline temperature was set at 32°C. The computer-controlled thermode system was programmed to gradually increase the stimulus (0.8°C/sec) until participants pressed a stop button, which indicates maximum tolerable temperature was reached and initiated immediate thermode cooling. The maximum tolerable temperature was recorded.

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold	46.58 degrees Celsius Standard Deviation 1.87

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for alertness/sedation ranges from 0 (almost asleep) to 100 (wide awake).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation	91.60 score on a scale Standard Deviation 16.33

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for energy level ranges from 0 (no energy) to 100 (full of energy).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level	89.60 score on a scale Standard Deviation 18.01

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for confusion ranges from 0 (clear headed) to 100 (confused).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion	1.60 score on a scale Standard Deviation 3.36

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for clumsiness ranges from 0 (well-coordinated) to 100 (extremely clumsy).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Clumsiness	2.60 score on a scale Standard Deviation 5.37

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for anxiety ranges from 0 (calm/relaxed) to 100 (extremely nervous).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Anxiety	1.50 score on a scale Standard Deviation 3.52

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for nausea ranges from 0 (no nausea) to 100 (worst nausea).

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Nausea	0.0 score on a scale Standard Deviation 0.0

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Measured in mmHg

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Maximum End-expired CO2 Concentration	37.40 mmHg Standard Deviation 1.91

SECONDARY outcome

Timeframe: 96 hours after dosing

Population: Participants who completed the study.

Maximum sedation score obtained via the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). The MOAA/S has a scale of 0 to 5, where 0 = "Does not respond to painful trapezius squeeze" and 5 = "Responds readily to name spoken in normal tone".

Outcome measures

Measure	Open Label Methadone IV n=19 Participants All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Pharmacodynamics (PD) in Adults - Maximum Sedation Score	5.0 score on a scale Standard Deviation 0.0

Adverse Events

Open Label Methadone IV

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Open Label Methadone IV n=22 participants at risk All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. Methadone hydrochloride 0.1mg/kg: Single dose of methadone hydrochloride administered via intravenous (IV)
Gastrointestinal disorders Nausea	27.3% 6/22 • Up to 96 hours (4 days)
Nervous system disorders Headache	18.2% 4/22 • Up to 96 hours (4 days)
Nervous system disorders Dizziness	4.5% 1/22 • Up to 96 hours (4 days)
Investigations Blood pressure diastolic abnormal	4.5% 1/22 • Up to 96 hours (4 days)
Investigations Blood pressure increased	4.5% 1/22 • Up to 96 hours (4 days)
Investigations Electrocardiogram QT prolonged	4.5% 1/22 • Up to 96 hours (4 days)
General disorders Injection site pain	4.5% 1/22 • Up to 96 hours (4 days)
Infections and infestations COVID-19	4.5% 1/22 • Up to 96 hours (4 days)

Additional Information

Kanecia Zimmerman

Duke University

Phone: 919-668-8651

Email: kanecia.zimmerman@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place