A Study to Evaluate Withdrawal Effects Following Dosing of Oxycodone/Naltrexone in Methadone-Maintained Subjects
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|ClinicalTrials.gov Identifier: NCT02391571|
Recruitment Status : Completed
First Posted : March 18, 2015
Last Update Posted : August 10, 2016
|Condition or disease||Intervention/treatment||Phase|
|Withdrawal Symptoms||Drug: Oxycodone/Naltrexone Capsules Drug: Oxycodone Drug: Placebo||Phase 3|
Approximately 34 methadone-maintained opioid-dependent subjects will be enrolled in the study. All subjects will be admitted to the clinical study unit (CSU; Visit 2) for a 15-day (with 14 overnight stays) inpatient Treatment Phase visit. Subjects will first undergo a 3-day methadone stabilization period (Days 1 to 3) in which all subjects' methadone administration time will be gradually shifted to the time of dosing that will be used throughout the Treatment Phase (approximately 8 am daily). Following the methadone dosing-time stabilization period, subjects will begin a 2-day oxycodone placebo administration period. On Day 4 and Day 5, all subjects will receive a total of 3 oxycodone placebo doses, separated by 6 hours each, starting from approximately one hour following methadone dose administration. Placebo will be administered in a single-blind manner. Starting on Day 6, subjects will be randomized in a 2:1 (Oxycodone/Naltrexone or Oxycodone) fashion to receive one of the following treatments in a double-blinded manner:
- Oxycodone/Naltrexone, multiple oral daily dosing for 5 days
- Oxycodone, multiple oral daily dosing for 5 days Subjects will receive one of the above-listed treatments three times daily, beginning approximately 1 hour following methadone dosing and every 6 hours until 3 doses have been administered. Subjects will be dosed in this manner for 5 consecutive days (Days 6 to 10). All subjects will remain confined in the CSU for 4 days after the first of three doses of study drug is administered on Day 10 for the safety/washout period, during which they will continue to be assessed and monitored for withdrawal effects. Subjects will be discharged approximately 96 hours after the first dose of study drug (oxycodone/naltrexone or oxycodone) administered on the morning of Day 10, if medically acceptable according to the investigator or designee. All subjects will receive daily phone calls until the Follow-up Phase during which subjects will be asked about the presence of withdrawal symptoms and any other adverse events (AEs).
On Days 4 to 9, safety, withdrawal, pharmacokinetic and pharmacodynamic assessments will be performed up to 13 hours after the first of the three daily study drug doses is administered. Following Day 10 study drug administration, assessments will be completed until 96 hours after the first of the three daily study drug doses is administered on the morning of Day 10.
The Follow-up Phase will be conducted approximately 10 to 14 days after the last drug administration on Day 10 or after early withdrawal from the study and will include standard safety assessments.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Multiple-Dose, Parallel Group Study to Evaluate the Potential of Withdrawal Effects Following Administration of Oxycodone/Naltrexone Capsules and Oxycodone in Methadone-Maintained Opioid-Dependent Subjects|
|Study Start Date :||February 2015|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||March 2015|
Oxycodone/Naltrexone Capsules (over-encapsulated), on days 6-10, every 6 hours (at 09:00, 15:00, 21:00)
Drug: Oxycodone/Naltrexone Capsules
Oxycodone/Naltrexone to be taken with stable dose of Methadone
Active Comparator: Oxycodone
Oxycodone Tablets (Over-encapsulated), on Days 6-10, every 6 hours (at 09:00, 15:00, 21:00)
Oxycodone to be taken with stable dose of Methadone
Placebo Lead-In: Placebo Capsules (matching to Active and Experimental) on days 4-5, every 6 hours (at 09:00, 15:00, 21:00)
2 day placebo run in prior to test and active drug phase of study
- Primary: Onset of Withdrawal measured by Subjective Opioid Withdrawal Scale(SOWS) [ Time Frame: up to 10 days ]To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Subjective Opioid Withdrawal Scale(SOWS), a set of 16 questions scored on a scale of 0-4 (not at all to extremely) according to how the subject feels at that moment to the questions asked about withdrawal symptoms. The questions are asked during the placebo period 9 times daily , and daily during treatment administration 9 times a day.
- Primary: Onset of Withdrawal measured by Clinician-Rated Opioid Withdrawal Scale (COWS) [ Time Frame: up to 10 days ]To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Clinician-Rated Opioid Withdrawal Scale (COWS), a set of 11 questions scored by a trained clinician that best describes the subject's signs or symptoms of withdrawal at that time. Each are rated on the apparent relationship to opiate withdrawal. These are assessed during the placebo period 9 times daily , and daily during treatment administration 9 times a day. A total score is tallied that determines mild, moderate, moderately severe or severe withdrawal.
- Secondary: Pharmacokinetic Profile of Naltrexone and 6β-Naltrexol in Subjects receiving Oxycodone/Naltrexone [ Time Frame: up to 14 days ]To investigate the multiple dose pharmacokinetics of naltrexone, and 6β-naltrexol following repeated daily administration of Oxycodone/Naltrexone in methadone-maintained opioid dependent subjects. All subjects enrolled will have 3 PK samples taken during the placebo period and 3-13 samples taken during days 6-10 of the study. Samples will also be taken during the wash-out period, 2 on Day 11, then daily through Day 14. T max, Cmax AUC Ctrough and apparent first-order terminal elimination half-life will be calculated as part of the PK profile.
- Secondary: Subjective Pharmacodynamic Effects through the use of Visual Analog Scales (VAS) [ Time Frame: up to 14 days ]To explore the pharmacodynamic effects of Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone maintained opioid-dependent subjects through the use of Visual Analog Scales (VAS) to rate Bad Effects, Feeling Sick and Any Effects at the moment of the scale being administered, with 0 mm being "Not At All" and 100 mm being "Extremely". These are administered during the placebo period 9 times daily , and daily during treatment administration 9 times a day. Also, the measurement will be taken during the wash-out period daily. All enrolled subjects will have the VAS measurements administered.
- Secondary: Objective Pharmacodynamic Effects through the use of Pupillometry measurements [ Time Frame: up to 14 days ]To explore the physiological effects of Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone maintained opioid-dependent subjects through the use of Pupillometry measurements. An electronic pupillometry will be used, and every effort will be made to use the same eye for each measurement. Measurements will be taken during the placebo period 9 times daily , and daily during treatment administration 9 times a day. Also, the measurement will be taken daily during the wash-out period. All enrolled subjects will have the pupillometry measurements taken.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02391571
|United States, Kansas|
|Vince and Associates|
|Overland Park, Kansas, United States, 66212|
|Principal Investigator:||Debra Kelsh, MD||Vince and Associates|