Cocaine Dependence
Conditions
Keywords
Cocaine-Related disorders, Cocaine, Substance-Related disorders, Opioid abuse, Opioid dependence, abuse, addiction, treatment, buprenorphine, naltrexone, Suboxone, Vivitrol
Brief summary
The aim of this study is to investigate the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence.
Detailed description
This project will assess the utility of buprenorphine in the presence of naltrexone as a potential medication useful in reducing cocaine use, commencing a research direction of great importance to both theoretical and practical addiction medicine. Buprenorphine will be provided as sublingual buprenorphine+naloxone tablets (Suboxone®, BUP). Naltrexone will be provided as extended-release (XR) naltrexone by injection (Vivitrol®, XR-NTX). In this multi-center, double-blind, placebo-controlled trial, participants will randomly assigned to one of three medication conditions: 4mg buprenorphine plus naltrexone (BUP4+XR-NTX), 16mg buprenorphine plus naltrexone (BUP16+XR-NTX), or placebo plus naltrexone (PLB+XR-NTX) for 8 weeks of treatment. Participants will be scheduled for clinic visits three times weekly (for a total of 24 visits across the 8-week treatment period) for observed medication administration, provision of take-home medication, collection of safety, medical, drug use, psychological, and compliance measures. In addition, all participants will be scheduled for once-weekly individual Cognitive Behavioral Therapy (CBT) sessions. This protocol will explore the effects of these three medication conditions to test buprenorphine as a possible treatment for cocaine dependence. This study will advance the science, provide dosing information, and characterize the effects of the combination of the two medications in this population.
Interventions
DRUGBuprenorphine + Naltrexone
Following a successful naloxone challenge, induction onto extended-release naltrexone by injection (Vivitrol®), and a final assessment of eligibility, participants will be randomly assigned to one of the three conditions: 4mg buprenorphine plus naltrexone, 16 mg buprenorphine plus naltrexone, or placebo plus naltrexone for 8 weeks of treatment. Random assignment will be on a 1:1:1 ratio to one of three conditions. Randomization will be stratified according to site and opioid use levels.
DRUGPlacebo + Naltrexone
Following a successful naloxone challenge, induction onto extended-release naltrexone by injection (Vivitrol®), and a final assessment of eligibility, participants will be randomly assigned to one of the three conditions: 4mg buprenorphine plus naltrexone, 16 mg buprenorphine plus naltrexone, or placebo plus naltrexone for 8 weeks of treatment. Random assignment will be on a 1:1:1 ratio to one of three conditions. Randomization will be stratified according to site and opioid use levels.
Sponsors
National Institute on Drug Abuse (NIDA)
The Emmes Company, LLC
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 65 years of age * In good general health * Meet Diagnostic and Statistical Manual (DSM)-IV criteria for cocaine dependence * Meet DSM-IV criteria for past-year opioid dependence OR past-year opioid abuse OR have past-year opioid use and a history of opioid dependence during the lifetime * Interested in receiving treatment for cocaine dependence * Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study * Able to satisfy and comply with study procedures and requirements * If female of childbearing potential, willing to practice and effective method of birth control for the duration of the study
Exclusion criteria
* Pregnant or breastfeeding females * Known allergy or sensitivity to study medications * Recent or ongoing treatment with medications that, in the judgment of the study medical clinician, could interact adversely with study drugs or interfere with study participation * Have a current pattern of alcohol, benzodiazepine, or other sedative-hypnotic use, as determined by the study medical clinician, which would preclude safe participation * Liver function test results greater than 5 times the upper limit of normal or other exclusionary clinical lab test values * Serious medical condition or acute psychiatric disorder that would make study participation difficult or unsafe * Pending action or situation that might prevent remaining in the area for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens | final 30 days of Treatment Phase, study days 25-54 | Self-reported days of cocaine use corroborated with urine drug screens (UDS). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BUP4+XR-NTX 4mg buprenorphine plus naltrexone for 8 weeks of treatment | 100 |
| BUP16+XR-NTX 16mg buprenorphine plus naltrexone for 8 weeks of treatment | 100 |
| PLB+XR-NTX Placebo plus naltrexone for 8 weeks of treatment | 102 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 4 |
| Overall Study | Incarcerated (N=3) | 2 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 11 | 11 |
Baseline characteristics
| Characteristic | PLB+XR-NTX | Total | BUP4+XR-NTX | BUP16+XR-NTX |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 102 Participants | 302 Participants | 100 Participants | 100 Participants |
| Age, Continuous | 46.5 years STANDARD_DEVIATION 7.68 | 46.3 years STANDARD_DEVIATION 8.63 | 46.8 years STANDARD_DEVIATION 8 | 45.8 years STANDARD_DEVIATION 10.08 |
| Age, Customized 18-24 | 0 years | 3 years | 0 years | 3 years |
| Age, Customized 25-34 | 7 years | 30 years | 9 years | 14 years |
| Age, Customized 35-44 | 26 years | 72 years | 27 years | 19 years |
| Age, Customized 45-54 | 55 years | 146 years | 46 years | 45 years |
| Age, Customized 55-64 | 14 years | 51 years | 18 years | 19 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 31 Participants | 12 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants | 271 Participants | 88 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 65 Participants | 191 Participants | 58 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 16 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 12 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) White | 27 Participants | 78 Participants | 26 Participants | 25 Participants |
| Region of Enrollment United States | 102 participants | 302 participants | 100 participants | 100 participants |
| Sex: Female, Male Female | 23 Participants | 65 Participants | 20 Participants | 22 Participants |
| Sex: Female, Male Male | 79 Participants | 237 Participants | 80 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 100 | 64 / 100 | 61 / 102 |
| serious Total, serious adverse events | 13 / 100 | 8 / 100 | 12 / 102 |
Outcome results
Primary
Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens
Self-reported days of cocaine use corroborated with urine drug screens (UDS).
Time frame: final 30 days of Treatment Phase, study days 25-54
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BUP4+XR-NTX | Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens | 6.6 days of cocaine use | Standard Deviation 5.25 |
| BUP16+XR-NTX | Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens | 7.2 days of cocaine use | Standard Deviation 6.77 |
| PLB+XR-NTX | Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens | 7.7 days of cocaine use | Standard Deviation 6.16 |