Opioid Use DisorderPhase 3NCT02537574
Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension)
A Phase 3 study testing NTX/BUP, NTX/PBO-B and PBO-N/PBO-B in people with Opioid Use Disorder, run by Alkermes, Inc. at 20 sites in United States.
Trial summary
This study will evaluate the safety, effectiveness and tolerance of low doses of oral naltrexone along with buprenorphine to treat opioid use disorder prior to the first injection of VIVITROL. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- NTX/BUP, NTX/PBO-B and PBO-N/PBO-B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 380 participants
- Where
- 20 sitesUnited States
- Study dates
- Aug 2015to 9 Jan 2017
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Willing and able to provide informed consent
- Willing and able to provide government-issued identification
- Has a BMI of 18.0-40.0 kg/m^2
- Has a physiologic dependence on opioids
- Is voluntarily seeking treatment for opioid use disorder and willing to completely withdraw from his/her opioid use throughout the study with desire for or motivation for antagonist therapy
- Wiling to abide by the contraception requirements for the duration of the study
- Additional criteria may apply
Who cannot join
- Is pregnant, planning to become pregnant or breastfeeding during the study
- Has used Buprenorphine within 7 days prior to randomization
- Has used Methadone within 14 days prior to randomization
- Has a history of VIVITROL use within 90 days prior to screening or has used oral naltrexone within 14 days prior to randomization
- Has a history of seizures or has received anticonvulsant therapy within the past 5 years
- Has a condition, disease state, or previous medical history that would preclude safe participation in the study or affect the ability to adhere to the protocol visit schedule, requirements, or assessments
Show all 15Show fewer
- Has a current diagnosis of schizoaffective disorder, bipolar disorder, or untreated and unstable major depressive disorder
- Is currently physiologically dependent on any psychoactive substance (except opioids, caffeine, or nicotine) requiring medical intervention for detoxification
- Has a history of hypersensitivity or adverse reaction to Buprenorphine, Naltrexone, or Naloxone
- Has a history of more than 3 unsuccessful inpatient or medically assisted outpatient opioid detoxifications during his/her lifetime
- Has significant suicidal ideation or behavior within the past year
- Is currently participating, or has participated, in a clinical trial of an investigational drug, device, or biologics within 3 months prior to screening
- Has a history of accidental opioid drug overdose in the past 3 years whether or not medical treatment was sought or received
- Is court mandated to receive treatment for opioid use disorder
- Additional criteria may apply
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
Community Clinical Research, Inc.
Austin, Texas, 78754
John Hopkins University School of Medicine
Baltimore, Maryland, 21224
Comprehensive Clinical Research
Berlin, New Jersey, 08009
Neuro-Behavioral Clinical Research, Inc.
Canton, Ohio, 44718
Midwest Clinical Research Center, LLC
Dayton, Ohio, 45417
Insite Clinical Research
DeSoto, Texas, 75115
Duke University Medical Center
Durham, North Carolina, 27705
Baylor College of Medicine
Houston, Texas, 77030
Atlantic Shores Hospital
Lauderhill, Florida, 33308
TRY Research
Maitland, Florida, 84107
PRA Health Sciences
Marlton, New Jersey, 08053
New York State Psychiatric Institute/ Columbia University
New York, New York, 10032
Research Centers of America
Oakland Park, Florida, 33334
North Country Clinical Research
Oceanside, California, 92056
NRC Research Institute
Orange, California, 92868
CNS Healthcare
Orlando, Florida, 32801
University Of Pennsylvania - Treatment Research Center
Philadelphia, Pennsylvania, 19104
Western Psychiatric Institute and Clinic of UPMC
Pittsburgh, Pennsylvania, 15213
Pharmaceutical Research Associates Inc.
Salt Lake City, Utah, 32751
Neuroscience Research Institute
Winfield, Illinois, 60190
About this study
Official title: A Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL®
This study will evaluate the safety, effectiveness and tolerance of low doses of oral naltrexone along with buprenorphine to treat opioid use disorder prior to the first injection of VIVITROL.
- Conditions
- Opioid Use Disorder
- Being tested
- NTX/BUP, NTX/PBO-B, PBO-N/PBO-B
- Keywords
- Alkermes, Buprenorphine, Naltrexone, Vivitrol, Opioid Use, Opiates, Dependence, Abuse, Heroin, Painkillers, Substance Abuse
- Medical subject headings
- Opioid-Related Disorders, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTX/BUPDrug
Daily doses
NTX/PBO-BDrug
Daily doses
PBO-N/PBO-BDrug
Daily doses
| Study group | Role | What they receive |
|---|---|---|
| NTX/BUP | Experimental | Oral naltrexone + sublingual buprenorphine Receives: Drug: NTX/BUP |
| NTX/PBO-B | Active comparator | Oral naltrexone + sublingual placebo Receives: Drug: NTX/PBO-B |
| PBO-N/PBO-B | Placebo comparator | Oral placebo naltrexone + sublingual placebo buprenorphine Receives: Drug: PBO-N/PBO-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection
Toleration to the injection was demonstrated by mild opioid withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] </=12 or Subjective Opiate Withdrawal Scale [SOWS] </=10) following VIVITROL administration. The COWS is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal. The SOWS is a 16-item self-report questionnaire designed to measure the severity of opioid withdrawal symptoms. The subject rates the intensity of symptoms using a 5-point scale. The range of SOWS scores is 1-10 (mild); 11-20 (moderate); and 21-30 (severe).
Measured: 1 week
Secondary outcomes (6)
Proportion of Days With COWS Peak Score of Less Than or Equal to 12 During the Treatment Period Prior to the VIVITROL Injection
The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal.
Measured: 1 week
Mean Peak COWS Score During Treatment Period Prior to VIVITROL Injection
The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal.
Measured: 1 week
Area Under the Curve (AUC) COWS Score During the Treatment Period Prior to VIVITROL Injection
The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal. To determine the daily AUC COWS score, a curve was generated by plotting the COWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC COWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC COWS score was then divided by the number of days with daily AUC COWS score during the treatment period. The AUC COWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Measured: The COWS was administered 4-6 times per day during the Treatment Period (Days 1-7)
Mean Score for Desire of Opioids During Treatment Period Prior to VIVITROL Injection
The Desire for Opioids Visual Analog Scale (VAS) uses a 100-mm, horizontal linear scale, with 0 anchored on the left representing "no desire for opioids" and 100 anchored on the right representing "strongest imaginable desire for opioids". Subjects placed a vertical line on the scale to indicate their desire for opioids at that particular time.
Measured: 1 week
Incidence of Adverse Effects
The number of subjects who experienced treatment-emergent Adverse Events.
Measured: Up to 92 days
Area Under the Curve SOWS Score During the Treatment Period Prior to the VIVITROL Injection
The Subjective Opiate Withdrawal Scale (SOWS) is a 16-item self-report questionnaire designed to measure the severity of opioid withdrawal symptoms. The subject rates the intensity of symptoms using a 5-point scale. The range of SOWS scores is 1-10 (mild); 11-20 (moderate); and 21-30 (severe). To determine the daily AUC SOWS score, a curve was generated by plotting the SOWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC SOWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC SOWS score was then divided by the number of days with daily AUC SOWS score during the treatment period. The AUC SOWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Measured: The SOWS was administered 4-6 times per day during the Treatment Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2015 (estimated)
- Study startAug 2015
- Primary completion27 Oct 2016
- Study completion9 Jan 2017
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 (2)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 380 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alkermes, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maria A. Sullivan, MD, PhD, Study director, Alkermes, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537574
- Sponsor's protocol ID
- ALK6428-A301
- Status last verified
- Mar 2019
- First submitted
- 31 Aug 2015
- Last updated
- 6 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bisaga A, Mannelli P, Yu M, Nangia N, Graham CE, Tompkins DA, Kosten TR, Akerman SC, Silverman BL, Sullivan MA. Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial. Drug Alcohol Depend. 2018 Jun 1;187:171-178. doi: 10.1016/j.drugalcdep.2018.02.023. Epub 2018 Apr 10.
PubMed 29674251Mannelli P, Douaihy AB, Zavod A, Legedza A, Akerman SC, Sullivan MA. Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone. Am J Drug Alcohol Abuse. 2021 Nov 2;47(6):753-759. doi: 10.1080/00952990.2021.1969659. Epub 2021 Nov 9.
PubMed 34752714
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL®
- ClinicalTrials.gov ID
- NCT02537574
- Acronym / sponsor ID
- ALK6428-A301
- Conditions
- Opioid Use Disorder
- Keywords
- Alkermes, Buprenorphine, Naltrexone, Vivitrol, Opioid Use, Opiates, Dependence, Abuse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 380 participants (actual)
- Lead sponsor
- Alkermes, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2015 (actual)
- Primary completion
- 27 Oct 2016 (actual)
- Study completion
- 9 Jan 2017 (actual)
- First posted
- 1 Sep 2015 (estimated)
- Results
- Posted 9 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, effectiveness and tolerance of low doses of oral naltrexone along with buprenorphine to treat opioid use disorder prior to the first injection of VIVITROL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NTX/BUP | Experimental | Drug: NTX/BUPOral naltrexone + sublingual buprenorphine |
| NTX/PBO-B | Active comparator | Drug: NTX/PBO-BOral naltrexone + sublingual placebo |
| PBO-N/PBO-B | Placebo comparator | Drug: PBO-N/PBO-BOral placebo naltrexone + sublingual placebo buprenorphine |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Willing and able to provide informed consent
- Willing and able to provide government-issued identification
- Has a BMI of 18.0-40.0 kg/m^2
- Has a physiologic dependence on opioids
- Is voluntarily seeking treatment for opioid use disorder and willing to completely withdraw from his/her opioid use throughout the study with desire for or motivation for antagonist therapy
Key exclusion criteria (15 listed)
- Is pregnant, planning to become pregnant or breastfeeding during the study
- Has used Buprenorphine within 7 days prior to randomization
- Has used Methadone within 14 days prior to randomization
- Has a history of VIVITROL use within 90 days prior to screening or has used oral naltrexone within 14 days prior to randomization
- Has a history of seizures or has received anticonvulsant therapy within the past 5 years
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 |
|---|---|---|
| NTX/BUPDaily doses | Drug | NTX/BUP |
| NTX/PBO-BDaily doses | Drug | NTX/PBO-B |
| PBO-N/PBO-BDaily doses | Drug | PBO-N/PBO-B |
Primary outcome
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection
Time frame: 1 week
Toleration to the injection was demonstrated by mild opioid withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] </=12 or Subjective Opiate Withdrawal Scale [SOWS] </=10) following VIVITROL administration. The COWS is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal. The SOWS is a 16-item self-report questionnaire designed to measure the severity of opioid withdrawal symptoms. The subject rates the intensity of symptoms using a 5-point scale. The range of SOWS scores is 1-10 (mild); 11-20 (moderate); and 21-30 (severe).
6 secondary outcomes
Proportion of Days With COWS Peak Score of Less Than or Equal to 12 During the Treatment Period Prior to the VIVITROL Injection
Time frame: 1 week
Mean Peak COWS Score During Treatment Period Prior to VIVITROL Injection
Time frame: 1 week
Area Under the Curve (AUC) COWS Score During the Treatment Period Prior to VIVITROL Injection
Time frame: The COWS was administered 4-6 times per day during the Treatment Period (Days 1-7)
Mean Score for Desire of Opioids During Treatment Period Prior to VIVITROL Injection
Time frame: 1 week
Incidence of Adverse Effects
Time frame: Up to 92 days
Area Under the Curve SOWS Score During the Treatment Period Prior to the VIVITROL Injection
Time frame: The SOWS was administered 4-6 times per day during the Treatment Period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29674251Bisaga A, Mannelli P, Yu M, Nangia N, Graham CE, Tompkins DA, Kosten TR, Akerman SC, Silverman BL, Sullivan MA. Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial. Drug Alcohol Depend. 2018 Jun 1;187:171-178. doi: 10.1016/j.drugalcdep.2018.02.023. Epub 2018 Apr 10.
- Derived from this study: PubMed 34752714Mannelli P, Douaihy AB, Zavod A, Legedza A, Akerman SC, Sullivan MA. Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone. Am J Drug Alcohol Abuse. 2021 Nov 2;47(6):753-759. doi: 10.1080/00952990.2021.1969659. Epub 2021 Nov 9.
Related trials for Opioid Use Disorder
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitationObservational study
Development of an Interview-Informed Timeline Follow-Back (TLFB) for Opioid Use in the Era of Fentanyl
Substance Use Disorders (SUDs)
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
Active, not recruitingPhase 2
Wellcome Leap Psilocybin for OUD
Opioid Use Disorder
Recruiting
Opioid and Pain Treatment in Indigenous Communities (OPTIC) Trial
Opioid Use Disorder, Opioid Misuse
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.
Maria A. Sullivan, MD, PhD study director
Alkermes, Inc.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NTX/BUP, NTX/PBO-B and PBO-N/PBO-B in people with Opioid Use Disorder, run by Alkermes, Inc. at 20 sites in United States.
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 7 inclusion and 15 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 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 9 Jan 2019). 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?
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection (time frame: 1 week). 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 NCT02537574, which also lists 2 linked publications.
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 6 Mar 2019.