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Efficacy of BNX Sublingual Tablets Versus BNX Sublingual Film for Treatment of Opioid-Dependent Adults (ISTART)

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ClinicalTrials.gov Identifier: NCT01908842
Recruitment Status : Completed
First Posted : July 26, 2013
Results First Posted : May 22, 2015
Last Update Posted : May 10, 2017
Sponsor:
Collaborator:
Worldwide Clinical Trials
Information provided by (Responsible Party):
Orexo AB

Brief 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. Secondary objectives included assessment of treatment effects on opioid withdrawal symptoms, opioid cravings, and safety.

Condition or disease Intervention/treatment Phase
Opioid Dependence, on Agonist Therapy Drug: BNX sublingual tablets Drug: BNX sublingual film Drug: Buprenorphine Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 759 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : August 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Buprenorphine; then OL BNX film, then BNX tablets
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
Drug: BNX sublingual tablets
Buprenorphine/naloxone sublingual tablets
Other Names:
  • OX219
  • Zubsolv

Drug: BNX sublingual film
Buprenorphine/naloxone sublingual film
Other Name: Suboxone film

Drug: Buprenorphine
Buprenorphine sublingual tablets
Other Name: Generic buprenorphine

Experimental: BNX tablets, then OL BNX tablets, then BNX film
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
Drug: BNX sublingual tablets
Buprenorphine/naloxone sublingual tablets
Other Names:
  • OX219
  • Zubsolv

Drug: BNX sublingual film
Buprenorphine/naloxone sublingual film
Other Name: Suboxone film




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Clinical Opiate Withdrawal Scale (COWS) Scores: Induction [ Time Frame: Days 1 and 2 ]
    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

  2. COWS Total Scores: Stabilization/Maintenance [ Time Frame: Days 3 through 22 ]
    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

  3. Subjective Opiate Withdrawal Scale (SOWS) Scores: Induction [ Time Frame: Days 1 and 2 ]
    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

  4. SOWS Total Scores: Stabilization/Maintenance [ Time Frame: Days 3 through 22 ]
    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

  5. Visual Analog Scale (VAS) Cravings: Induction [ Time Frame: Days 1 and 2 ]
    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")

  6. VAS Craving Scores: Stabilization/Maintenance [ Time Frame: Days 3 through 22 ]
    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")



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male/female 18-65 years old
  2. Able to read, comprehend & sign the informed consent form
  3. Meet opioid dependence criteria in DSM-IV-TR the past 12 months
  4. Have a buprenorphine-negative UDS &/or urine dipstick
  5. Prepared to abstain from opioids other than the study drug & from other addictive drugs
  6. Negative urine pregnancy test
  7. 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
  8. Clearance from the prescribing MD to be withdrawn from their prescribed opioids for subjects receiving opioids for pain
  9. Lack of clinically significant abnormalities in health assessments performed at screening. Unclear cases should be approved by the medical monitor
  10. At least mild withdrawal symptoms (COWS ≥9)

Exclusion Criteria:

  1. Pregnant, lactating or planning to be pregnant during study
  2. 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
  3. Prescribed treatment with generic buprenorphine monotherapy within 90 days prior start of treatment
  4. 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
  5. Participating in other clinical studies in which medications is delivered or who have used an investigational drug/device within the last 30 days
  6. 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
  7. Staff, affiliated with, or family member of the staff directly involved with this study
  8. Serious untreated Axis I DSM-IV-TR psychiatric comorbidity (actively suicidal or homicidal, have untreated schizophrenia)
  9. Tongue/oral deformities that may affect the absorption of the drug products
  10. 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
  11. HIV-seropositive with a CD4+ count <200, active AIDS defining infection in the last 120 days
  12. Have Class III/IV congestive heart failure, symptomatic myocardial ischemia or history of long QT syndrome (or an immediate family member with this condition)
  13. Currently taking Class 1A antiarrhythmic medications (e.g., quinidine, procainamide, & disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, & dofetilide)
  14. Have uncontrolled hypertension, pulse oximetry ≤92%or clinically significant abnormality on 12-lead ECG, including a corrected QT (QTc) interval >450 ms
  15. Severe liver disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01908842


  Show 36 Study Locations
Sponsors and Collaborators
Orexo AB
Worldwide Clinical Trials
Investigators
Principal Investigator: Erik Gunderson University of Virginia, PO Box 800623, Charlottesville, VA 22911

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Orexo AB
ClinicalTrials.gov Identifier: NCT01908842     History of Changes
Other Study ID Numbers: OX219-006 Protocol Amendment 4
First Posted: July 26, 2013    Key Record Dates
Results First Posted: May 22, 2015
Last Update Posted: May 10, 2017
Last Verified: April 2017

Keywords provided by Orexo AB:
Opioid
Dependence
agonist
buprenorphine
naloxone
BUP/NAL

Additional relevant MeSH terms:
Buprenorphine
Buprenorphine, Naloxone Drug Combination
Naloxone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists