Opioid DependencePhase 3PRO-814NCT02180659
A Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily SL Buprenorphine to Probuphine® Subdermal Implants
A Phase 3 study testing sublingual buprenorphine tablets and Buprenorphine implant in people with Opioid Dependence, run by Titan Pharmaceuticals.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Dependence
- What is being tested?
- sublingual buprenorphine tablets and Buprenorphine implant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 177 participants
- Where
- No sites listed yet
- Study dates
- Jul 2014to May 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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).
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- 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.
About this study
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
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.
Read the 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).
- Conditions
- Opioid Dependence
- Being tested
- sublingual buprenorphine tablets, Buprenorphine implant, placebo implants, sublingual placebo tablets
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sublingual buprenorphine tabletsDrug
Buprenorphine implantDrug
placebo implantsDrug
sublingual placebo tabletsDrug
| Study group | Role | What they receive |
|---|---|---|
| buprenorphine implants + placebo tablets | Experimental | Four 80 mg Probuphine implants + daily SL placebo tablets Receives: Drug: Buprenorphine implant; Drug: sublingual placebo tablets |
| buprenorphine tablets + placebo implants | Active comparator | Daily SL BPN tablets (≤8 mg/daily) + four placebo implants Receives: Drug: sublingual buprenorphine tablets; Drug: placebo implants |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Titan Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02180659
- Sponsor's protocol ID
- PRO-814
- Acronym
- PRO-814
- Status last verified
- Nov 2018
- First submitted
- 1 Jul 2014
- Last updated
- 11 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27434441
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02180659
- Acronym / sponsor ID
- PRO-814 / PRO-814
- Conditions
- Opioid Dependence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Titan PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 3 Jul 2014 (estimated)
- Results
- Posted 5 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| buprenorphine implants + placebo tablets | Experimental | Drug: Buprenorphine implant, Drug: sublingual placebo tabletsFour 80 mg Probuphine implants + daily SL placebo tablets |
| buprenorphine tablets + placebo implants | Active comparator | Drug: sublingual buprenorphine tablets, Drug: placebo implantsDaily SL BPN tablets (≤8 mg/daily) + four placebo implants |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Free from significant withdrawal symptoms (score of ≤ 5 on the Clinical Opiate Withdrawal Scale [COWS]), as measured at the Screening Visit.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sublingual buprenorphine tablets | Drug | buprenorphine tablets + placebo implants |
| Buprenorphine implant | Drug | buprenorphine implants + placebo tablets |
| placebo implants | Drug | buprenorphine tablets + placebo implants |
| sublingual placebo tablets | Drug | buprenorphine implants + placebo tablets |
Primary outcome
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.
Time frame: 24 weeks
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.
7 secondary outcomes
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
Time frame: 24 weeks
Percent of Subjects With no Self-reported Illicit Drug Use by Month
Time frame: 24 weeks
Measures of Craving: Desire to Use Visual Analogue Scale (VAS)
Time frame: 24 weeks
Measures of Withdrawal: Clinical Opiate Withdrawal Scale (COWS)
Time frame: 24 weeks
Measures of Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) (ITT Population)
Time frame: 24 weeks
Measures of Craving: Need to Use Visual Analogue Scale (VAS)
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27434441Rosenthal 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sublingual buprenorphine tablets and Buprenorphine implant in people with Opioid Dependence, run by Titan Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02180659, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2019.