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

Phase 2

Completed

Interventions: 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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Medisorb naltrexone 75 mg	Hydromorphone (10 mg/mL)	-
Medisorb naltrexone 150 mg	Hydromorphone (10 mg/mL)	-
Medisorb naltrexone 150 mg	Naloxone Challenge and Oral Naltrexone Tolerability Testing	-
Medisorb naltrexone 75 mg	Medisorb naltrexone 75 mg	-
Medisorb naltrexone 75 mg	Naloxone Challenge and Oral Naltrexone Tolerability Testing	-
Medisorb naltrexone 150 mg	Medisorb naltrexone 150 mg	-
Medisorb naltrexone 300 mg	Medisorb naltrexone 300 mg	-
Medisorb naltrexone 300 mg	Hydromorphone (10 mg/mL)	-
Medisorb naltrexone 300 mg	Naloxone Challenge and Oral Naltrexone Tolerability Testing	-

Primary Outcome Measures

Name	Time	Method
Slope Change From Baseline for Pupil Size	4 weeks (Baseline to Day 28)	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.

Secondary Outcome Measures