Clinical trial NCT01218984: ALK21-004: Single-dose Opiate Challenge of Medisorb® Naltrexone (VIVITROL®) in Adults Who Use Opioids
Official title: A Randomized, Single-Dose Opiate Challenge Study of Medisorb® Naltrexone in Opioid-Using Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opiate Dependence
Keywords: Opiate Dependence
Lead sponsor: Alkermes, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-13
Enrollment: 27
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Slope Change From Baseline for Pupil Size
timeFrame: 4 weeks (Baseline to Day 28)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Alkermes, Inc.
name: Bernard L. Silverman, MD
role: STUDY_DIRECTOR
References:
citation: Bigelow GE, Preston KL, Schmittner J, Dong Q, Gastfriend DR. Opioid challenge evaluation of blockade by extended-release naltrexone in opioid-abusing adults: dose-effects and time-course. Drug Alcohol Depend. 2012 Jun 1;123(1-3):57-65. doi: 10.1016/j.drugalcdep.2011.10.018. Epub 2011 Nov 12.