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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PBO NTX + BUP | Active Comparator | Placebo naltrexone + buprenorphine |
|
| NTX + BUP | Experimental | Naltrexone + buprenorphine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naltrexone | Drug | daily dosing |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8 | Demonstrated by mild opioid withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] \ | 8 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maria A. Sullivan, MD, PhD | Alkermes, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Segal Institute for Clinical Research | Lauderhill | Florida | 33308 | United States | ||
| Research Centers of America, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35137481 | Derived | Mannelli P, Douaihy AB, Akerman SC, Legedza A, Fratantonio J, Zavod A, Sullivan MA. Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting. Am J Addict. 2022 Mar;31(2):142-147. doi: 10.1111/ajad.13264. Epub 2022 Feb 9. | |
| 34752714 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | NTX + BUP | Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing |
| FG001 | PBO NTX + BUP | Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 14, 2017 | Oct 31, 2018 |
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| Drug |
daily dosing |
|
| Buprenorphine | Drug | daily dosing |
|
| 1 week |
| Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | COWS score \ | Days 9-11 |
| 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). | Up to 7 days |
| 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. | The COWS was administered 4-6 times per day during the Treatment Period |
| 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." | Up to 11 days |
| Incidence of Adverse Events (AEs) | Number and percentage of subjects who experienced AEs. | Up to 42 days |
| Oakland Park |
| Florida |
| 33334 |
| United States |
| Neuroscience Research Institute, Inc. | Winfield | Illinois | 60190 | United States |
| John Hopkins School of Medicine | Baltimore | Maryland | 21205-1911 | United States |
| Hassman Research Institute | Berlin | New Jersey | 08009 | United States |
| New York State Psychiatric Institute | New York | New York | 10032 | United States |
| Duke University Medical Center | Durham | North Carolina | 27705 | United States |
| University of Pennsylvania Treatment Research Center | Philadelphia | Pennsylvania | 19104 | United States |
| Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Mannelli P, Douaihy AB, Zavod A, Legedza A, Akerman SC, Sullivan MA. Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone. Am J Drug Alcohol Abuse. 2021 Nov 2;47(6):753-759. doi: 10.1080/00952990.2021.1969659. Epub 2021 Nov 9. |
| 32777606 | Derived | Kosten T, Aharonovich E, Nangia N, Zavod A, Akerman SC, Lopez-Bresnahan M, Sullivan MA. Cognitive performance of patients with opioid use disorder transitioned to extended-release injectable naltrexone from buprenorphine: Post hoc analysis of exploratory results of a phase 3 randomized controlled trial. Addict Behav. 2020 Dec;111:106538. doi: 10.1016/j.addbeh.2020.106538. Epub 2020 Jul 3. |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NTX + BUP | Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing |
| BG001 | PBO NTX + BUP | Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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] \ | 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. | Posted | Count of Participants | Participants | 8 days |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Mean | Standard Deviation | Days | 1 week |
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| Secondary | Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | COWS score \ | 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. | Posted | Mean | Standard Deviation | Days | Days 9-11 |
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| 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). | 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. | Posted | Mean | Standard Deviation | score on a scale | Up to 7 days |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | The COWS was administered 4-6 times per day during the Treatment Period |
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| 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." | All randomized subjects who received at least 1 dose of study drug and provided at least 1 post-baseline measureable VAS assessment. | Posted | Mean | Standard Deviation | score on a scale | Up to 11 days |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Incidence of Adverse Events (AEs) | Number and percentage of subjects who experienced AEs. | 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. | Posted | Count of Participants | Participants | Up to 42 days |
|
|
Adverse event data were collected over a period of 42 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NTX + BUP | Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing | 0 | 50 | 0 | 50 | 36 | 50 |
| EG001 | PBO NTX + BUP | Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing | 0 | 51 | 1 | 51 | 34 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal Ideation | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Psychotic Disorder | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Drug Withdrawal Syndrome | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Restless Legs Syndrome | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
|
Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eva Stroynowski | Alkermes | 781-609-7000 | Eva.Stroynowski@alkermes.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 29, 2017 | Oct 31, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| D016739 | Behavior, Addictive |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D003192 | Compulsive Behavior |
| D007175 | Impulsive Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| D002047 | Buprenorphine |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
Not provided
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| Participants |
|
|
|
|
Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing |
|
|
|
|