Drug Dependence, Opiate Dependence
Conditions
Brief summary
Post-marketing commitment to the European Medicines Agency to conduct a prospective, controlled study of the transfer from Subutex to Suboxone.
Interventions
DRUGSuboxone, Buprenorphine Hydrochloride + Naloxone, SCH 484
Suboxone sublingual tablet 4 mg/1 mg - 24 mg/6 mg, daily for 28 days
DRUGSubutex, Buprenorphine Hydrochloride, SCH 28444
Subutex sublingual tablet 4-24 mg, daily for 28 days
Sponsors
Indivior Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be males or non-pregnant, non-lactating females. * Subjects must be at least 15 years of age, of either sex, and any race. * Subjects (and/or the parent or guardian for subjects under the age of legal consent or who otherwise are unable to provide independent consent) must demonstrate willingness to participate in the study and to adhere to dose and visit schedules. * Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria(18) for opioid dependence. * Subjects must have been receiving maintenance treatment with Subutex at doses ranging from 4 mg to the maximum dose permitted by country labeling requirements, but not to exceed 24 mg/day, for at least 1 month prior to screening. * Subjects must not, according to self-report, have injected opioids more than four times in the month prior to screening. * Subjects must have an opioid-negative urine drug screening (UDS) result prior to randomization. * Each subject must confirm that he or she is practicing adequate contraception. * Female subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (β-hCG) test prior to enrollment in the study.
Exclusion criteria
* Subjects for whom treatment with either Subutex or Suboxone as required in the protocol would be inconsistent with national labeling. * Subjects who are unwilling or unable to comply with the requirements of the protocol (eg, pending incarceration) or are in a situation or condition that, in the opinion of the investigator, may interfere with participation in the study. * Subjects who are participating in any other clinical study in which medication(s) are being delivered. * Subjects with known allergy or sensitivity to naloxone. * Subjects who are on the staff, affiliated with, or a family member of the staff personnel directly involved with this study. * Subjects must not have serious untreated Axis I DSM-IV-TR psychiatric comorbidity (eg, those who are actively suicidal or homicidal, have untreated schizophrenia, etc). Polysubstance abuse or dependence will not exclude subjects except in the case of unauthorized and significant benzodiazepine use requiring medical detoxification or alcohol dependence requiring medical detoxification. * Human immunodeficiency virus (HIV)-positive subjects with clinical acquired immunodeficiency syndrome (AIDS). * Subjects treated with generic buprenorphine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Assessed by Day 7 of double-blind, double-dummy treatment period. | Response rate was defined as the percentage of participants who did not receive a dose increase from the dose given at the first dosing date by Day 7 of a one-week, randomized, double-blind, double-dummy treatment transfer phase. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Suboxone Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone during Weeks 2-4 with weekly access to take-home doses as of Week 2. | 143 |
| Subutex Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex during Weeks 2-4 with weekly access to take-home doses as of Week 2. | 97 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Suboxone | Subutex | Total |
|---|---|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 8.2 | 35.5 years STANDARD_DEVIATION 8.7 | 35.7 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 30 Participants | 22 Participants | 52 Participants |
| Sex: Female, Male Male | 113 Participants | 75 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 143 | 52 / 97 |
| serious Total, serious adverse events | 2 / 143 | 4 / 97 |
Outcome results
Primary
Response Rate
Response rate was defined as the percentage of participants who did not receive a dose increase from the dose given at the first dosing date by Day 7 of a one-week, randomized, double-blind, double-dummy treatment transfer phase.
Time frame: Assessed by Day 7 of double-blind, double-dummy treatment period.
Population: Analysis of primary outcome was done on the intention-to-treat (ITT) population, defined as all randomized subjects who took at least one dose of study medication and provided at least one valid post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suboxone | Response Rate | 83.2 Percentage of participants |
| Subutex | Response Rate | 88.7 Percentage of participants |
95% CI: [-0.142, 0.034]Binomial approximation