Back to resultsA Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily SL Buprenorphine to Probuphine® Subdermal Implants (PRO-814)
Primary Purpose
Opioid Dependence
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
sublingual buprenorphine tablets
Buprenorphine implant
placebo implants
sublingual placebo tablets
Sponsored by
About this trial
This is an interventional treatment trial for Opioid Dependence
Eligibility Criteria
Inclusion Criteria:
- Subject must provide written informed consent prior to the conduct of any study-related procedures.
- Male or female, 18-65 years of age, inclusive.
- Primary diagnosis of opioid dependence (DSM-IV-TR).
Subject is considered clinically stable by their treating healthcare provider and confirmed by the following:
- Subject must be on SL BPN treatment for at least 6 months.
- Subject must have been on a SL BPN dose of 8 mg or less daily for at least the last 90 days prior to Screening.
- No positive urine toxicology results for illicit opioids in the last 90 days.
- Free from significant withdrawal symptoms (score of ≤ 5 on the Clinical Opiate Withdrawal Scale [COWS]), as measured at the Screening Visit.
- Female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire study (Screening Visit to Follow-Up Visit).
Exclusion Criteria:
- Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS).
- Current diagnosis of chronic pain syndrome requiring chronic opioid treatment, or conditions associated with acute episodic flares that require opioid treatment.
- Pregnant or lactating or planning to become pregnant during the study.
- Hypersensitivity or allergy to ethylene vinyl acetate (EVA)-containing substances or naloxone.
- Recent scarring or tattoos on their upper arms, or a history of keloid scarring.
- Requires current use of agents metabolized through CYP 3A4 such as azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir).
- History of coagulopathy within the past 90 days, and/or current anti-coagulant therapy such as warfarin.
- Current DSM-IV-TR diagnosis for substance dependence on any other psychoactive substances other than opioids or nicotine (e.g., alcohol, cocaine).
- Significant symptoms or other factors which in the opinion of the Investigator would preclude compliance with the protocol, subject safety, adequate cooperation in the study, or obtaining informed consent.
- Current medical conditions such as severe respiratory insufficiency that may prevent the subject from safely participating in study.
- Any pending legal action that could prohibit participation or compliance in the study.
- Exposure to any investigational drug within the 8 weeks prior to Screening.
- Aspartate aminotransferase levels ≥3 X the upper limit of normal, alanine aminotransferase levels ≥ 3 X the upper limit of normal, total bilirubin ≥ 1.5 X the upper limit of normal, or creatinine ≥ 1.5 X upper limit of normal on the Screening laboratory assessments.
- Clinically significant low platelet count on the Screening laboratory assessments, according to the Investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
buprenorphine implants + placebo tablets
buprenorphine tablets + placebo implants
Arm Description
Four 80 mg Probuphine implants + daily SL placebo tablets
Daily SL BPN tablets (≤8 mg/daily) + four placebo implants
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
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.
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.
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02180659
Brief Title
A Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily SL Buprenorphine to Probuphine® Subdermal Implants
Acronym
PRO-814
Official Title
A Randomized, Double-Blind, Double-Dummy, Active-Controlled Multicenter Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily Maintenance Dose of 8 mg or Less of Sublingual Buprenorphine or Buprenorphine/Naloxone to Four Probuphine® Subdermal Implants
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Titan Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Dependence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
177 (Actual)
8. Arms, Groups, and Interventions
Arm Title
buprenorphine implants + placebo tablets
Arm Type
Experimental
Arm Description
Four 80 mg Probuphine implants + daily SL placebo tablets
Arm Title
buprenorphine tablets + placebo implants
Arm Type
Active Comparator
Arm Description
Daily SL BPN tablets (≤8 mg/daily) + four placebo implants
Intervention Type
Drug
Intervention Name(s)
sublingual buprenorphine tablets
Intervention Type
Drug
Intervention Name(s)
Buprenorphine implant
Intervention Type
Drug
Intervention Name(s)
placebo implants
Intervention Type
Drug
Intervention Name(s)
sublingual placebo tablets
Primary Outcome Measure Information:
Title
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.
Description
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
Secondary Outcome Measure Information:
Title
Percent of Subjects With no Urine Illicit Opioid Use by Month;
Description
The secondary outcome is the percent of subjects with no urine illicit opioid use by month.
Time Frame
24 weeks
Title
Number of Participants With Evidence of Urine Illicit Opioid Use by Month
Description
Secondary efficacy endpoint measures number of participants with evidence of urine illicit opioid use by month.
Time Frame
24 weeks
Title
Percent of Subjects With no Self-reported Illicit Drug Use by Month
Description
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
Title
Measures of Craving: Desire to Use Visual Analogue Scale (VAS)
Description
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
Title
Measures of Withdrawal: Clinical Opiate Withdrawal Scale (COWS)
Description
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.
Time Frame
24 weeks
Title
Measures of Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) (ITT Population)
Description
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
Title
Measures of Craving: Need to Use Visual Analogue Scale (VAS)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject must provide written informed consent prior to the conduct of any study-related procedures.
Male or female, 18-65 years of age, inclusive.
Primary diagnosis of opioid dependence (DSM-IV-TR).
Subject is considered clinically stable by their treating healthcare provider and confirmed by the following:
Subject must be on SL BPN treatment for at least 6 months.
Subject must have been on a SL BPN dose of 8 mg or less daily for at least the last 90 days prior to Screening.
No positive urine toxicology results for illicit opioids in the last 90 days.
Free from significant withdrawal symptoms (score of ≤ 5 on the Clinical Opiate Withdrawal Scale [COWS]), as measured at the Screening Visit.
Female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire study (Screening Visit to Follow-Up Visit).
Exclusion Criteria:
Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS).
Current diagnosis of chronic pain syndrome requiring chronic opioid treatment, or conditions associated with acute episodic flares that require opioid treatment.
Pregnant or lactating or planning to become pregnant during the study.
Hypersensitivity or allergy to ethylene vinyl acetate (EVA)-containing substances or naloxone.
Recent scarring or tattoos on their upper arms, or a history of keloid scarring.
Requires current use of agents metabolized through CYP 3A4 such as azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir).
History of coagulopathy within the past 90 days, and/or current anti-coagulant therapy such as warfarin.
Current DSM-IV-TR diagnosis for substance dependence on any other psychoactive substances other than opioids or nicotine (e.g., alcohol, cocaine).
Significant symptoms or other factors which in the opinion of the Investigator would preclude compliance with the protocol, subject safety, adequate cooperation in the study, or obtaining informed consent.
Current medical conditions such as severe respiratory insufficiency that may prevent the subject from safely participating in study.
Any pending legal action that could prohibit participation or compliance in the study.
Exposure to any investigational drug within the 8 weeks prior to Screening.
Aspartate aminotransferase levels ≥3 X the upper limit of normal, alanine aminotransferase levels ≥ 3 X the upper limit of normal, total bilirubin ≥ 1.5 X the upper limit of normal, or creatinine ≥ 1.5 X upper limit of normal on the Screening laboratory assessments.
Clinically significant low platelet count on the Screening laboratory assessments, according to the Investigator.
12. IPD Sharing Statement
Citations:
PubMed Identifier
27434441
Citation
Rosenthal RN, Lofwall MR, Kim S, Chen M, Beebe KL, Vocci FJ; PRO-814 Study Group. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA. 2016 Jul 19;316(3):282-90. doi: 10.1001/jama.2016.9382.
Results Reference
derived
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A Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily SL Buprenorphine to Probuphine® Subdermal Implants
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