The primary objective of the study is to demonstrate maintenance of treatment efficacy when transferring adult outpatients with opioid dependence, who are clinically stabilized on 8 mg or less of sublingual (SL) buprenorphine (BPN), to 4 Probuphine implants compared to SL BPN. The secondary objective of the study is to confirm safety of 4 Probuphine implants in adult outpatients with opioid dependence who are clinically stabilized on 8 mg or less of SL BPN.
This is a randomized, double-blind, double-dummy, active-controlled multi-center study to evaluate the efficacy of transition to four 80 mg Probuphine implants in adult outpatients with opioid dependence, who are clinically stabilized on 8 mg or less of SL BPN. The study will include 3 Phases; Screening, Maintenance and Follow-up. Medical and eligibility screening should occur within 2 weeks of the first Maintenance Phase visit. The Screening Visit will include standard medical screening procedures, complete medical/psychosocial history, urine toxicology and detailed substance use and treatment history. All subjects who have provided written informed consent and have met the other study entry criteria will be eligible for randomization. Following confirmation of eligibility, subjects will be randomized to one of two treatment groups in a 1:1 ratio: * Treatment Group A: Daily SL BPN tablets (≤8 mg/daily) + four placebo implants * Treatment Group B: Four 80 mg Probuphine implants + daily SL placebo tablets Implants will be surgically inserted on Day 1 (Baseline and Initiation of Study Drugs Visit). On Post-Implant Visit, additional follow-up safety and implant assessment procedures will be conducted. Subjects will return for monthly study visits on Weeks 4, 8, 12, 16, 20, and 24 (End of Treatment Visit). In addition to the monthly scheduled visits, subjects will provide 4 random urine toxicology samples throughout the 24-week treatment period. A total of 10 urine toxicology samples will be collected; 6 at scheduled visits (1 per month) and 4 at random urine toxicology visits throughout the 24-week treatment period. At the scheduled visits, other assessments of efficacy and safety will be collected. Implants will be removed at the End of Treatment Visit on Week 24. Following Week 24, subjects will be re-transitioned back to usual care (pre-trial), as needed. During Week 25, telephone contact will be made with all subjects. and Week 26 will include an on-site visit to the clinic for final follow-up assessments (Follow-up Visit).
Study Type
INTERVENTIONAL
Allocation
The Primary Efficacy Endpoint is a Responder Rate Analysis, Where a Responder is Defined as a Patient With no More Than 2 of 6 Months With Any Evidence of Illicit Opioid Use.
The primary efficacy endpoint is a responder analysis. A subject will be designated as a responder (meaning they have maintained stability) if they have no more than 2 of 6 months with any evidence of illicit opioid use. Evidence of illicit opioid use is defined as a positive opioid urine toxicology result or self-reported illicit opioid use.
Time frame: 24 weeks
Percent of Subjects With no Urine Illicit Opioid Use by Month;
The secondary outcome is the percent of subjects with no urine illicit opioid use by month.
Time frame: 24 weeks
Number of Participants With Evidence of Urine Illicit Opioid Use by Month
Secondary efficacy endpoint measures number of participants with evidence of urine illicit opioid use by month.
Time frame: 24 weeks
Percent of Subjects With no Self-reported Illicit Drug Use by Month
Subjects in the ITT population with no self-reported use of any illicit drugs (opioid or non-opioid) by month of evaluation
Time frame: 24 weeks
Measures of Craving: Desire to Use Visual Analogue Scale (VAS)
The secondary outcome of measures of craving: desire to use is a change from Day 1 (baseline) in the unipolar visual analogue scale (VAS), which is a 0-100 mm scale, where 0 mm is no desire, and 100 mm is strongest possible desire.
Time frame: 24 weeks
Measures of Withdrawal: Clinical Opiate Withdrawal Scale (COWS)
The secondary outcome measures the change in baseline in the Clinical opiate withdrawal scale (COWS), which is a scale consisting of 11 common opiate withdrawal signs or symptoms, rated on a numeric scale with higher scores associated with greater withdrawal symptoms. A total score was calculated as the sum of the responses to the 11 signs/symptoms for a total range of 0-48. Withdrawal severity was classified, based on the total score, as follows: 0-4=none/normal, 5-12=mild, 13-24=moderate, 25-36=moderately severe, more than 36=severe withdrawal.
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RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
177
Time frame: 24 weeks
Measures of Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) (ITT Population)
The secondary outcome measures the change in baseline in the subjective opioid withdrawal scale (SOWS), which is a scale which is a subject self-assessment of withdrawal symptoms. The scale consists of 16 questions that rate the intensity of withdrawal from 0 (not at all) to 4 (extremely) with a cumulative score ranging from 0-64 (0 =not at all, 64=extremely)
Time frame: 24 weeks
Measures of Craving: Need to Use Visual Analogue Scale (VAS)
The secondary outcome of measures of craving: Need to use is a change from Day 1 (baseline) in the unipolar visual analogue scale (VAS), which is a 0-100 mm scale, where 0 mm is no need, and 100 mm is strongest possible need.
Time frame: 24 weeks