Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| Pro00106216 | Other Identifier | Duke site IRB# |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Single-center, open label, single-session study to evaluate methadone pharmacokinetics and pharmacodynamic in adults.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm, Open label Methadone IV | Experimental | All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| methadone hydrochloride 0.1mg/kg | Drug | Single dose of methadone hydrochloride administered via intravenous (IV) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry | 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. | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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
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)
Females who are pregnant or nursing
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kanecia Zimmerman, MD, MPH,PhD | DUMC, DCRI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke Early Phase Unit (DEPRU | Durham | North Carolina | 27710 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetics (PK) in Adults - Systemic Clearance (CL) | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | liters/hour | 96 hours after dosing |
|
|
Up to 96 hours (4 days)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kanecia Zimmerman | Duke University | 919-668-8651 | kanecia.zimmerman@duke.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 27, 2023 | Jan 13, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 18, 2023 | Mar 20, 2024 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
Not provided
Not provided
| ID | Term |
|---|---|
| D008691 | Methadone |
| ID | Term |
|---|---|
| D007659 | Ketones |
| D009930 | Organic Chemicals |
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| 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 |
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. |
| 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation | 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). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level | 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). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion | Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for confusion ranges from 0 (clear headed) to 100 (confused). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Clumsiness | 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). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Anxiety | 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). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Nausea | 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). | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Maximum End-expired CO2 Concentration | Measured in mmHg | 96 hours after dosing |
| Pharmacodynamics (PD) in Adults - Maximum Sedation Score | 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". | 96 hours after dosing |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
| Primary | Pharmacokinetics (PK) in Adults - Volume of Distribution | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | liters | 96 hours after dosing |
|
|
|
| Primary | Pharmacokinetics (PK) in Adults - Elimination Half-life | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | hours | 96 hours after dosing |
|
|
|
| Primary | 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. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | ng*h/mL | 96 hours after dosing |
|
|
|
| Primary | Pharmacokinetics (PK) in Adults - AUC0-inf | AUC0-inf is the area under the curve from time 0 extrapolated to infinite time. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | ng*h/mL | 96 hours after dosing |
|
|
|
| Primary | 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. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | ng/mL | 96 hours after dosing |
|
|
|
| Primary | Pharmacokinetics (PK) in Adults - Tmax | Tmax is the time corresponding to maximum concentration post-dose. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | hours | 96 hours after dosing |
|
|
|
| Primary | Pharmacokinetics (PK) in Adults - Cmin | Cmin is the observed minimum concentration post-dose. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | ng/mL | 96 hours after dosing |
|
|
|
| Primary | 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. | Participants with samples collected at 96 hours. | Posted | Mean | Standard Deviation | h^-1 | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | mm | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold | 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. | Participants who completed the study. | Posted | Mean | Standard Deviation | degrees Celsius | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation | 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). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level | 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). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion | Subjective self-assessment of methadone effects using a visual analog scale (VAS). The score for confusion ranges from 0 (clear headed) to 100 (confused). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Clumsiness | 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). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Anxiety | 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). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Nausea | 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). | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Maximum End-expired CO2 Concentration | Measured in mmHg | Participants who completed the study. | Posted | Mean | Standard Deviation | mmHg | 96 hours after dosing |
|
|
|
| Secondary | Pharmacodynamics (PD) in Adults - Maximum Sedation Score | 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". | Participants who completed the study. | Posted | Mean | Standard Deviation | score on a scale | 96 hours after dosing |
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 10 |
| 22 |
| Headache | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
|
| Blood pressure diastolic abnormal | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |