Opioid Use Disorder
Conditions
Keywords
naltrexone, VIVITROL, buprenorphine, opioid, addiction
Brief summary
This study will evaluate the efficacy, safety, and tolerability of oral naltrexone used in conjunction with buprenorphine in adults with Opioid Use Disorder transitioning from buprenorphine maintenance prior to the first dose of VIVITROL.
Interventions
DRUGNaltrexone
daily dosing
DRUGPlacebo
daily dosing
DRUGBuprenorphine
daily dosing
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide informed consent * Willing and able to provide government-issued identification * Has a Body Mass Index (BMI) of 18.0-40.0 kg/m\^2 * Has a history of opioid use disorder diagnosis for at least 6 months * Has a history of prescribed buprenorphine (or buprenorphine/naloxone) maintenance for the prior 3 or more consecutive months and is currently buprenorphine-maintained * Must be voluntarily seeking treatment for opioid use disorder and be motivated to receive antagonist therapy * Willing to abide by the contraception requirements for the duration of the study * Additional criteria may apply
Exclusion criteria
* Is pregnant, planning to become pregnant or breastfeeding during the study * Has a positive urine drug screen for opiates or oxycodone at screening * Has used methadone within 30 days prior to study Day -5 * Has used naltrexone (oral or VIVITROL) within the 90 days prior to Day -5 * Has a history of seizures or has received anticonvulsant therapy within the past 5 years for treatment of seizures (use of anticonvulsant during the past detoxification is not exclusionary) * 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 * 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, VIVITROL, or naloxone * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8 | 8 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | Days 9-11 | COWS score \</=12; 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). |
| Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7) | Up to 7 days | 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). |
| Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection | 1 week | 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). |
| Mean Score for Desire for Opioids Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | Up to 11 days | The Desire for Opioids 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. |
| Incidence of Adverse Events (AEs) | Up to 42 days | Number and percentage of subjects who experienced AEs. |
| Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | The COWS was administered 4-6 times per day during the Treatment Period | 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). The daily AUC COWS score is derived based on the actual time (unit in minutes) COWS administered on each day by using the linear trapezoidal rule, and then divided by the COWS administration duration (last COWS administration time minus first COWS administration time) for that day. The normalized AUC COWS score is the summation of daily AUC COWS score during the relevant period divided by the number of days with daily AUC COWS score. |
Countries
United States
Participant flow
Pre-assignment details
There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
Participants by arm
| Arm | Count |
|---|---|
| NTX + BUP Naltrexone + buprenorphine
Naltrexone: daily dosing
Buprenorphine: daily dosing | 50 |
| PBO NTX + BUP Placebo naltrexone + buprenorphine
Placebo: daily dosing
Buprenorphine: daily dosing | 51 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 12 |
Baseline characteristics
| Characteristic | NTX + BUP | Total | PBO NTX + BUP |
|---|---|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 9.41 | 35.6 years STANDARD_DEVIATION 8.53 | 34.8 years STANDARD_DEVIATION 7.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 96 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 93 Participants | 47 Participants |
| Region of Enrollment United States | 50 participants | 101 participants | 51 participants |
| Sex: Female, Male Female | 14 Participants | 30 Participants | 16 Participants |
| Sex: Female, Male Male | 36 Participants | 71 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 |
| other Total, other adverse events | 36 / 50 | 34 / 51 |
| serious Total, serious adverse events | 0 / 50 | 1 / 51 |
Outcome results
Primary
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8
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).
Time frame: 8 days
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NTX + BUP | Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8 | 35 Participants |
| PBO NTX + BUP | Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8 | 38 Participants |
p-value: 0.40795% CI: [0.28, 1.68]Regression, Logistic
Secondary
Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
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). The daily AUC COWS score is derived based on the actual time (unit in minutes) COWS administered on each day by using the linear trapezoidal rule, and then divided by the COWS administration duration (last COWS administration time minus first COWS administration time) for that day. The normalized AUC COWS score is the summation of daily AUC COWS score during the relevant period divided by the number of days with daily AUC COWS score.
Time frame: The COWS was administered 4-6 times per day during the Treatment Period
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTX + BUP | Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | 4.5 score on a scale | Standard Deviation 3.11 |
| PBO NTX + BUP | Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | 3.9 score on a scale | Standard Deviation 2.29 |
Secondary
Incidence of Adverse Events (AEs)
Number and percentage of subjects who experienced AEs.
Time frame: Up to 42 days
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. All the efficacy analyses are summarized by the planned treatment assignment, and all the safety analyses are summarized by actual treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NTX + BUP | Incidence of Adverse Events (AEs) | 38 Participants |
| PBO NTX + BUP | Incidence of Adverse Events (AEs) | 37 Participants |
Secondary
Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7)
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).
Time frame: Up to 7 days
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTX + BUP | Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7) | 6.0 score on a scale | Standard Deviation 3.71 |
| PBO NTX + BUP | Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7) | 5.0 score on a scale | Standard Deviation 2.78 |
Secondary
Mean Score for Desire for Opioids Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
The Desire for Opioids 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.
Time frame: Up to 11 days
Population: All randomized subjects who received at least 1 dose of study drug and provided at least 1 post-baseline measureable VAS assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTX + BUP | Mean Score for Desire for Opioids Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | 6.3 score on a scale | Standard Deviation 12.62 |
| PBO NTX + BUP | Mean Score for Desire for Opioids Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | 8.3 score on a scale | Standard Deviation 14.43 |
Secondary
Proportion of Days With COWS Peak Score </=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).
Time frame: 1 week
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTX + BUP | Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection | 5.8 Days | Standard Deviation 1.61 |
| PBO NTX + BUP | Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection | 6.3 Days | Standard Deviation 1.36 |
Secondary
Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal
COWS score \</=12; 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).
Time frame: Days 9-11
Population: There is one subject who was randomized to the naltrexone + buprenorphine treatment arm, but mistakenly received placebo naltrexone + buprenorphine treatment. This subject is categorized in the PBO NTX+BUP arm in the participant flow and safety analyses, but in the efficacy analyses the subject is categorized as NTX+BUP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTX + BUP | Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | 2.4 Days | Standard Deviation 0.87 |
| PBO NTX + BUP | Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | 2.6 Days | Standard Deviation 0.81 |