Opioid Dependence, on Agonist TherapyPhase 3ISTARTNCT01908842
Efficacy of BNX Sublingual Tablets Versus BNX Sublingual Film for Treatment of Opioid-Dependent Adults
A Phase 3 study testing BNX sublingual tablets, BNX sublingual film and Buprenorphine in people with Opioid Dependence, on Agonist Therapy, run by Orexo AB at 36 sites in United States.
Trial summary
The purpose of this study was to assess retention in treatment after induction with buprenorphine/naloxone (BNX) sublingual tablets compared with generic buprenorphine and after stabilization with BNX sublingual tablets compared with BNX film. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Dependence, on Agonist Therapy
- What is being tested?
- BNX sublingual tablets, BNX sublingual film and Buprenorphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 759 participants
- Where
- 36 sitesUnited States
- Study dates
- Aug 2013to Apr 2014
- 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
- Male/female 18-65 years old
- Able to read, comprehend \& sign the informed consent form
- Meet opioid dependence criteria in DSM-IV-TR the past 12 months
- Have a buprenorphine-negative UDS \&/or urine dipstick
- Prepared to abstain from opioids other than the study drug \& from other addictive drugs
- Negative urine pregnancy test
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- Females of childbearing potential who use a reliable method of contraception. Females of non-childbearing potential; surgically sterile or post-menopausal as defined by being at least 50 years of age \& having an absence of menses for at least 2 years
- Clearance from the prescribing MD to be withdrawn from their prescribed opioids for subjects receiving opioids for pain
- Lack of clinically significant abnormalities in health assessments performed at screening. Unclear cases should be approved by the medical monitor
- At least mild withdrawal symptoms (COWS ≥9)
Who cannot join
- Pregnant, lactating or planning to be pregnant during study
- Unwilling/unable to comply with the requirements of the protocol (e.g., pending incarceration) are in a situation/condition that may interfere with participation in the study
- Prescribed treatment with generic buprenorphine monotherapy within 90 days prior start of treatment
- Daily dose of methadone over 30 mg during the past week or who received the last dose of methadone less than 30 hours prior to treatment
- Participating in other clinical studies in which medications is delivered or who have used an investigational drug/device within the last 30 days
- Allergy, sensitivity or intolerance to BUP, NAL or any related drug; history of drug hypersensitivity or intolerance which, in the opinion of the investigator, would compromise the safety of the subject/study
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- Staff, affiliated with, or family member of the staff directly involved with this study
- Serious untreated Axis I DSM-IV-TR psychiatric comorbidity (actively suicidal or homicidal, have untreated schizophrenia)
- Tongue/oral deformities that may affect the absorption of the drug products
- Current/history of clinically significant medical disorder or condition which would jeopardize the safety or impact the validity of the results. Unclear cases should be discussed with \& approved by the medical monitor
- HIV-seropositive with a CD4+ count <200, active AIDS defining infection in the last 120 days
- Have Class III/IV congestive heart failure, symptomatic myocardial ischemia or history of long QT syndrome (or an immediate family member with this condition)
- Currently taking Class 1A antiarrhythmic medications (e.g., quinidine, procainamide, \& disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, \& dofetilide)
- Have uncontrolled hypertension, pulse oximetry ≤92%or clinically significant abnormality on 12-lead ECG, including a corrected QT (QTc) interval >450 ms
- Severe liver disease
Trial locations and contacts
36 sites in 1 country.
36 sites in 1 country
United States36 sites
Study site
Allegheny County, Pennsylvania
Study site
Baldwin County, Alabama
Study site
Baltimore County, Maryland
Study site
Benton County, Washington
Study site
Beverly Hills, California
Study site
Bristol County, Massachusetts
Study site
Broward County, Florida
Study site
Caddo Parish, Louisiana
Study site
Camden County, New Jersey
Study site
Charleston County, South Carolina
Study site
Charlottesville Metropolitan Area, Virginia
Study site
Chicagoland, Illinois
Study site
Colombia County, Florida
Study site
Dallas County, Texas
Study site
DeKalb County, Georgia
Study site
Delaware County, Pennsylvania
Study site
Duval County, Florida
Study site
Greater Metro Orlando, Florida
Study site
Houston County, Alabama
Study site
Johnson County, Kansas
Study site
Kenton County, Kentucky
Study site
Lake County, Florida
Study site
Los Angeles County, California
Study site
Maricopa, Arizona
Study site
Miami-Dade County, Florida
Study site
Oklahoma County, Oklahoma
Study site
Osceola County, Florida
Study site
Palm Beach County, Florida
Study site
Philadelphia County, Pennsylvania
Study site
Portland Metropolitan Area, Oregon
Study site
Riverside County, California
Study site
Saint Louis Metro Area, Missouri
Study site
Salt Lake County, Utah
Study site
San Diego County, California
Study site
Warren County, New Jersey
Study site
Warren County, Ohio
About this study
Official title: Induction, STabilization, Adherence, and Retention Trial (ISTART) - A Randomized, Non-inferiority, Multicenter Study to Assess Early Treatment Efficacy of OX219 Versus SUBOXONE Film and to Explore Switching Between Treatments
The purpose of this study was to assess retention in treatment after induction with buprenorphine/naloxone (BNX) sublingual tablets compared with generic buprenorphine and after stabilization with BNX sublingual tablets compared with BNX film. Secondary objectives included assessment of treatment effects on opioid withdrawal symptoms, opioid cravings, and safety.
Read the detailed description
This prospective, randomized, multicenter, parallel-group, non-inferiority study was conducted at 43 centers in the United States from August 2013 to April 2014. A non-inferior design was used because both products contain the same active components, and it was considered unethical to include a placebo arm. The study comprised an induction phase of 2 days and a stabilization phase of 20 days, with study visits scheduled on Days 1, 2, 3, 4, 8, 15, and 22. Eligible opioid-dependent patients were randomly assigned within 14 days of screening to induction with either the BNX sublingual tablets or generic buprenorphine tablets for 2 days. On Day 3, patients initially allocated to buprenorphine were switched to BNX film, whereas those allocated to BNX sublingual tablets continued on the same treatment. On Day 15, patients receiving BNX film were switched to BNX sublingual tablets, and those on BNX sublingual tablets were switched to BNX film. At the final study visit on Day 22, patients were offered the option of continuing in an open-label follow-up study of BNX sublingual tablets.
- Conditions
- Opioid Dependence, on Agonist Therapy
- Being tested
- BNX sublingual tablets, BNX sublingual film, Buprenorphine
- Keywords
- Opioid, Dependence, agonist, buprenorphine, naloxone, BUP/NAL
- 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.
BNX sublingual tabletsDrug
Also called OX219, Zubsolv
Buprenorphine/naloxone sublingual tablets
BNX sublingual filmDrug
Also called Suboxone film
Buprenorphine/naloxone sublingual film
BuprenorphineDrug
Also called Generic buprenorphine
Buprenorphine sublingual tablets
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine; then OL BNX film, then BNX tablets | Active comparator | Days 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets Receives: Drug: BNX sublingual tablets; Drug: BNX sublingual film; Drug: Buprenorphine |
| BNX tablets, then OL BNX tablets, then BNX film | Experimental | Days 1-2: BNX sublingual tablets (blinded); Days 3 to 14: BNX sublingual tablets (open-label); Days 15-21: Buprenorphine/naloxone sublingual film (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets Receives: Drug: BNX sublingual tablets; Drug: BNX sublingual film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoints of Retention in Treatment at Days 3 and 15
Retention rates (number of patients retained) for the primary efficacy endpoints of retention in treatment at Days 3 and 15, which was defined as the number of patients who received treatment on Days 3 and 15.
Measured: Day 3 and Day 15
Secondary outcomes (6)
Clinical Opiate Withdrawal Scale (COWS) Scores: Induction
Absolute ± mean standard deviation values for COWS total scores at baseline; 0.5 h, 1.5 h, 3 h, and 6 h post dose on Day 1, and Day 2; COWS scores range from 0-48, with a lower score being more favorable
Measured: Days 1 and 2
COWS Total Scores: Stabilization/Maintenance
Absolute ± mean standard deviation values for COWS total scores at Days 3, 4, 8, 15, and 22; COWS scores range from 0-48, with a lower score being more favorable
Measured: Days 3 through 22
Subjective Opiate Withdrawal Scale (SOWS) Scores: Induction
Absolute ± mean standard deviation values for SOWS total scores at baseline, 0.5 h, 1.5 h, 3 h, and 6 h post dose on Day 1, and Day 2; SOWS score ranges from 0-64, with a lower score being more favorable
Measured: Days 1 and 2
SOWS Total Scores: Stabilization/Maintenance
Absolute ± mean standard deviation values for SOWS total scores on Days 2, 3, 4, 8, 15, and 22; SOWS scores ranged from 0-64, with a lower score being more favorable
Measured: Days 3 through 22
Visual Analog Scale (VAS) Cravings: Induction
Absolute mean ± standard deviation values for VAS cravings at baseline, 0.5 h, 1.5 h, 3 h, and 6 post dose on Day 1, and Day 2; the VAS craving scores range from 0 ("no cravings") to 100 ("most intense craving I have ever had")
Measured: Days 1 and 2
VAS Craving Scores: Stabilization/Maintenance
Absolute mean ± standard deviation values for VAS cravings scores on Days 3, 4, 8, 15, and 22; the VAS craving scores range from 0 ("no cravings") to 100 ("most intense craving I have ever had")
Measured: Days 3 through 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionApr 2014
- Study completionApr 2014
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 Dependence, on Agonist TherapyStudies 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
- 759 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orexo AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Responsible party
- Sponsor
- Investigators
- Erik Gunderson, Principal investigator, University of Virginia, PO Box 800623, Charlottesville, VA 22911
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01908842
- Sponsor's protocol ID
- OX219-006 Protocol Amendment 4
- Acronym
- ISTART
- Status last verified
- Apr 2017
- First submitted
- 19 Jul 2013
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gunderson EW, Hjelmstrom P, Sumner M; 006 Study Investigators. Effects of a higher-bioavailability buprenorphine/naloxone sublingual tablet versus buprenorphine/naloxone film for the treatment of opioid dependence during induction and stabilization: a multicenter, randomized trial. Clin Ther. 2015 Oct 1;37(10):2244-55. doi: 10.1016/j.clinthera.2015.08.025. Epub 2015 Sep 26.
PubMed 26412801
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction, STabilization, Adherence, and Retention Trial (ISTART) - A Randomized, Non-inferiority, Multicenter Study to Assess Early Treatment Efficacy of OX219 Versus SUBOXONE Film and to Explore Switching Between Treatments
- ClinicalTrials.gov ID
- NCT01908842
- Acronym / sponsor ID
- ISTART / OX219-006 Protocol Amendment 4
- Conditions
- Opioid Dependence, on Agonist Therapy
- Keywords
- Opioid, Dependence, agonist, buprenorphine, naloxone, BUP/NAL
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 759 participants (actual)
- Lead sponsor
- Orexo ABIndustry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Study start
- Aug 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 26 Jul 2013 (estimated)
- Results
- Posted 22 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to assess retention in treatment after induction with buprenorphine/naloxone (BNX) sublingual tablets compared with generic buprenorphine and after stabilization with BNX sublingual tablets compared with BNX film. Secondary objectives included assessment of treatment effects on opioid withdrawal symptoms, opioid cravings, and safety.
Detailed description
This prospective, randomized, multicenter, parallel-group, non-inferiority study was conducted at 43 centers in the United States from August 2013 to April 2014. A non-inferior design was used because both products contain the same active components, and it was considered unethical to include a placebo arm. The study comprised an induction phase of 2 days and a stabilization phase of 20 days, with study visits scheduled on Days 1, 2, 3, 4, 8, 15, and 22. Eligible opioid-dependent patients were randomly assigned within 14 days of screening to induction with either the BNX sublingual tablets or generic buprenorphine tablets for 2 days. On Day 3, patients initially allocated to buprenorphine were switched to BNX film, whereas those allocated to BNX sublingual tablets continued on the same treatment. On Day 15, patients receiving BNX film were switched to BNX sublingual tablets, and those on BNX sublingual tablets were switched to BNX film. At the final study visit on Day 22, patients were offered the option of continuing in an open-label follow-up study of BNX sublingual tablets.
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; then OL BNX film, then BNX tablets | Active comparator | Drug: BNX sublingual tablets, Drug: BNX sublingual film, Drug: BuprenorphineDays 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets |
| BNX tablets, then OL BNX tablets, then BNX film | Experimental | Drug: BNX sublingual tablets, Drug: BNX sublingual filmDays 1-2: BNX sublingual tablets (blinded); Days 3 to 14: BNX sublingual tablets (open-label); Days 15-21: Buprenorphine/naloxone sublingual film (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male/female 18-65 years old
- Able to read, comprehend \& sign the informed consent form
- Meet opioid dependence criteria in DSM-IV-TR the past 12 months
- Have a buprenorphine-negative UDS \&/or urine dipstick
- Prepared to abstain from opioids other than the study drug \& from other addictive drugs
Key exclusion criteria (15 listed)
- Pregnant, lactating or planning to be pregnant during study
- Unwilling/unable to comply with the requirements of the protocol (e.g., pending incarceration) are in a situation/condition that may interfere with participation in the study
- Prescribed treatment with generic buprenorphine monotherapy within 90 days prior start of treatment
- Daily dose of methadone over 30 mg during the past week or who received the last dose of methadone less than 30 hours prior to treatment
- Participating in other clinical studies in which medications is delivered or who have used an investigational drug/device within the last 30 days
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 |
|---|---|---|
| BNX sublingual tabletsAlso: OX219, ZubsolvBuprenorphine/naloxone sublingual tablets | Drug | BNX tablets, then OL BNX tablets, then BNX film, Buprenorphine; then OL BNX film, then BNX tablets |
| BNX sublingual filmAlso: Suboxone filmBuprenorphine/naloxone sublingual film | Drug | BNX tablets, then OL BNX tablets, then BNX film, Buprenorphine; then OL BNX film, then BNX tablets |
| BuprenorphineAlso: Generic buprenorphineBuprenorphine sublingual tablets | Drug | Buprenorphine; then OL BNX film, then BNX tablets |
Primary outcome
Primary Endpoints of Retention in Treatment at Days 3 and 15
Time frame: Day 3 and Day 15
Retention rates (number of patients retained) for the primary efficacy endpoints of retention in treatment at Days 3 and 15, which was defined as the number of patients who received treatment on Days 3 and 15.
6 secondary outcomes
Clinical Opiate Withdrawal Scale (COWS) Scores: Induction
Time frame: Days 1 and 2
COWS Total Scores: Stabilization/Maintenance
Time frame: Days 3 through 22
Subjective Opiate Withdrawal Scale (SOWS) Scores: Induction
Time frame: Days 1 and 2
SOWS Total Scores: Stabilization/Maintenance
Time frame: Days 3 through 22
Visual Analog Scale (VAS) Cravings: Induction
Time frame: Days 1 and 2
VAS Craving Scores: Stabilization/Maintenance
Time frame: Days 3 through 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26412801Gunderson EW, Hjelmstrom P, Sumner M; 006 Study Investigators. Effects of a higher-bioavailability buprenorphine/naloxone sublingual tablet versus buprenorphine/naloxone film for the treatment of opioid dependence during induction and stabilization: a multicenter, randomized trial. Clin Ther. 2015 Oct 1;37(10):2244-55. doi: 10.1016/j.clinthera.2015.08.025. Epub 2015 Sep 26.
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.
Erik Gunderson principal investigator
University of Virginia, PO Box 800623, Charlottesville, VA 22911
36 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 BNX sublingual tablets, BNX sublingual film and Buprenorphine in people with Opioid Dependence, on Agonist Therapy, run by Orexo AB at 36 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 10 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 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 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. 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 22 May 2015). 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?
Primary Endpoints of Retention in Treatment at Days 3 and 15 (time frame: Day 3 and Day 15). 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 NCT01908842, 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 10 May 2017.