ALK21-004: Single-dose Opiate Challenge of Medisorb® Naltrexone (VIVITROL®) in Adults Who Use Opioids

Study Overview
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Brief Summary
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This was a Phase 2, multicenter, randomized, double-blind pilot study in opioid-using adults to assess the presence, duration, and degree of opiate blockade as well as the safety and tolerability of Medisorb® naltrexone (VIVITROL®). Subjects were randomized in a 1:1:1 ratio to receive a single gluteal intramuscular (IM) injection of Medisorb naltrexone 75, 150, or 300 mg.

Detailed Description
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Potential subjects were screened within 21 days prior to dosing of study drug (Medisorb naltrexone or placebo) on Day 0. Screening evaluations included a baseline hydromorphone challenge session in which increasing doses of hydromorphone (0 mg [placebo], 3 mg, 4.5 mg, and 6 mg) were administered at hourly intervals to produce a cumulative dose-response curve. Throughout the 4-hour challenge period, subject-rated measures (Visual Analog Scale [VAS] questions) and physiological measures (ie, pupil size) were recorded. As a safety measure, at least 7 days after the baseline hydromorphone challenge, a naloxone challenge was performed followed by a 1-day oral naltrexone tolerability assessment. On Day 0, eligible subjects were administered a single dose of study drug. To assess the level of opiate blockade and surmountability attributable to Medisorb naltrexone, experimental hydromorphone challenge sessions were conducted postdose at Days 7, 14, 21, 28, 42, and 56, with a single placebo hydromorphone challenge administered at a randomly selected visit. Pupil size was measured 15 minutes prior to the first hydromorphone dose and at 15, 30, 45, and minutes after each ascending hydromorphone/placebo for hydromorphone dose. Blood samples for measurement of naltrexone and 6B-naltrexol were obtained at screening and before hydromorphone/placebo administration on Days 7, 14, 21, 28, 42, and 56. Subjects were monitored for safety through Day 56.

Official Title
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A Randomized, Single-Dose Opiate Challenge Study of Medisorb® Naltrexone in Opioid-Using Adults

Conditions
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Opiate Dependence

Intervention / Treatment
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* Drug: Medisorb naltrexone 75 mg
* Drug: Medisorb naltrexone 150 mg
* Drug: Medisorb naltrexone 300 mg
* Drug: Hydromorphone (10 mg/mL)
* Drug: Naloxone Challenge and Oral Naltrexone Tolerability Testing


Participation Criteria
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Eligibility Criteria
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Primary Inclusion Criteria: Adults who had used opioids: non-medically for at least 1 year; at least once per week for at least some period during their use history; and fewer than 3 times per week on average for the 30 days prior to screening. Provided written informed consent Demonstrated a positive response to hydromorphone challenge during screening Willing to use contraception for study duration if of childbearing potential Primary Exclusion Criteria: Any clinically significant medical condition or laboratory abnormality at screening Participated in a clinical trial within prior 30 days Dependent on opioids Seeking treatment for opioid abuse Psychosis or any major mood or anxiety disorder Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medisorb naltrexone 75 mg<br> | Drug: Medisorb naltrexone 75 mg<br>* Single administration via intramuscular (IM) injection.<br>* Other names: Naltrexone for extended-release injectable suspension;Drug: Hydromorphone (10 mg/mL)<br>* Increasing doses of 0, 3, 4.5, and 6 mg were administered at baseline (pre-study drug administration). After study drug administration, additional hydromorphone challenge sessions consisting of administering 0, 3, 4.5, and 6 mg were administered at 1-hr intervals at each of the postdose evaluation visits. In addition, at a randomly selected evaluation visit, subjects received four 0 mg (placebo) doses at 1-hour intervals.<br>* Other names: opioid agonist;Drug: Naloxone Challenge and Oral Naltrexone Tolerability Testing<br>* Administered according to the instructions provided by the respective manufacturer. Testing occurred at least 7 days after the baseline hydromorphone challenge and prior to study drug administration.<br>* Other names: ReVia® (oral naltrexone);|
| Experimental: Medisorb naltrexone 150 mg<br> | Drug: Medisorb naltrexone 150 mg<br>* Single administration via IM injection.<br>* Other names: Naltrexone for extended-release injectable suspension;Drug: Hydromorphone (10 mg/mL)<br>* Increasing doses of 0, 3, 4.5, and 6 mg were administered at baseline (pre-study drug administration). After study drug administration, additional hydromorphone challenge sessions consisting of administering 0, 3, 4.5, and 6 mg were administered at 1-hr intervals at each of the postdose evaluation visits. In addition, at a randomly selected evaluation visit, subjects received four 0 mg (placebo) doses at 1-hour intervals.<br>* Other names: opioid agonist;Drug: Naloxone Challenge and Oral Naltrexone Tolerability Testing<br>* Administered according to the instructions provided by the respective manufacturer. Testing occurred at least 7 days after the baseline hydromorphone challenge and prior to study drug administration.<br>* Other names: ReVia® (oral naltrexone);|
| Experimental: Medisorb naltrexone 300 mg<br> | Drug: Medisorb naltrexone 300 mg<br>* Single administration via IM injection.<br>* Other names: Naltrexone for extended-release injectable suspension;Drug: Hydromorphone (10 mg/mL)<br>* Increasing doses of 0, 3, 4.5, and 6 mg were administered at baseline (pre-study drug administration). After study drug administration, additional hydromorphone challenge sessions consisting of administering 0, 3, 4.5, and 6 mg were administered at 1-hr intervals at each of the postdose evaluation visits. In addition, at a randomly selected evaluation visit, subjects received four 0 mg (placebo) doses at 1-hour intervals.<br>* Other names: opioid agonist;Drug: Naloxone Challenge and Oral Naltrexone Tolerability Testing<br>* Administered according to the instructions provided by the respective manufacturer. Testing occurred at least 7 days after the baseline hydromorphone challenge and prior to study drug administration.<br>* Other names: ReVia® (oral naltrexone);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope Change From Baseline for Pupil Size | Photographs of subjects' pupils were measured horizontally and vertically, 15 minutes before the first hydromorphone dose and every 15 minutes after each hydromorphone/placebo for hydromorphone dose, for up to 1 hour. Size was the product of vertical and horizontal measures. The slope, determined by linear regression, was used as a summary measure of the dose-response relationship between the hydromorphone dose and pupil size. The steeper the slope, the greater the hydromorphone effect. A slope of zero indicated no evidence of a hydromorphone effect. | 4 weeks (Baseline to Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opiate Dependence