Trial Outcomes & Findings for Evaluating Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL (NCT NCT02696434)

Last Updated: 2019-02-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

101 participants

Primary outcome timeframe

8 days

Results posted on

2019-02-12

Participant Flow

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.

Participant milestones

Participant milestones
Measure	NTX + BUP Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Overall Study STARTED	50	51
Overall Study COMPLETED	28	33
Overall Study NOT COMPLETED	22	18

Reasons for withdrawal

Reasons for withdrawal
Measure	NTX + BUP Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Overall Study Adverse Event	3	1
Overall Study Lost to Follow-up	5	4
Overall Study Withdrawal by Subject	14	12
Overall Study Physician Decision	0	1

Baseline Characteristics

Evaluating Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NTX + BUP n=50 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=51 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing	Total n=101 Participants Total of all reporting groups
Age, Continuous	36.3 years STANDARD_DEVIATION 9.41 • n=5 Participants	34.8 years STANDARD_DEVIATION 7.58 • n=7 Participants	35.6 years STANDARD_DEVIATION 8.53 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	48 Participants n=7 Participants	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	47 Participants n=7 Participants	93 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants	51 participants n=7 Participants	101 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	NTX + BUP n=51 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=50 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8	35 Participants	38 Participants

SECONDARY outcome

Timeframe: 1 week

Outcome measures

Outcome measures
Measure	NTX + BUP n=51 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=50 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection	5.8 Days Standard Deviation 1.61	6.3 Days Standard Deviation 1.36

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	NTX + BUP n=51 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=50 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
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	2.6 Days Standard Deviation 0.81

SECONDARY outcome

Timeframe: Up to 7 days

Outcome measures

Outcome measures
Measure	NTX + BUP n=51 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=50 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7)	6.0 score on a scale Standard Deviation 3.71	5.0 score on a scale Standard Deviation 2.78

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	NTX + BUP n=51 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=50 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
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	3.9 score on a scale Standard Deviation 2.29

SECONDARY outcome

Timeframe: 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.

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."

Outcome measures

Outcome measures
Measure	NTX + BUP n=45 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=46 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
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	8.3 score on a scale Standard Deviation 14.43

SECONDARY outcome

Timeframe: 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.

Number and percentage of subjects who experienced AEs.

Outcome measures

Outcome measures
Measure	NTX + BUP n=50 Participants Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=51 Participants Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Incidence of Adverse Events (AEs)	38 Participants	37 Participants

Adverse Events

NTX + BUP

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

PBO NTX + BUP

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NTX + BUP n=50 participants at risk Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=51 participants at risk Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Psychiatric disorders Suicidal Ideation	0.00% 0/50 • Adverse event data were collected over a period of 42 days	2.0% 1/51 • Number of events 1 • Adverse event data were collected over a period of 42 days
Psychiatric disorders Psychotic Disorder	0.00% 0/50 • Adverse event data were collected over a period of 42 days	2.0% 1/51 • Number of events 2 • Adverse event data were collected over a period of 42 days

Other adverse events

Additional Information

Eva Stroynowski

Alkermes

Phone: 781-609-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	NTX + BUP n=50 participants at risk Naltrexone + buprenorphine Naltrexone: daily dosing Buprenorphine: daily dosing	PBO NTX + BUP n=51 participants at risk Placebo naltrexone + buprenorphine Placebo: daily dosing Buprenorphine: daily dosing
Psychiatric disorders Anxiety	30.0% 15/50 • Number of events 15 • Adverse event data were collected over a period of 42 days	29.4% 15/51 • Number of events 15 • Adverse event data were collected over a period of 42 days
Psychiatric disorders Insomnia	26.0% 13/50 • Number of events 14 • Adverse event data were collected over a period of 42 days	25.5% 13/51 • Number of events 13 • Adverse event data were collected over a period of 42 days
Psychiatric disorders Restlessness	8.0% 4/50 • Number of events 4 • Adverse event data were collected over a period of 42 days	9.8% 5/51 • Number of events 5 • Adverse event data were collected over a period of 42 days
Psychiatric disorders Drug Withdrawal Syndrome	6.0% 3/50 • Number of events 5 • Adverse event data were collected over a period of 42 days	3.9% 2/51 • Number of events 2 • Adverse event data were collected over a period of 42 days
Gastrointestinal disorders Diarrhoea	32.0% 16/50 • Number of events 16 • Adverse event data were collected over a period of 42 days	17.6% 9/51 • Number of events 9 • Adverse event data were collected over a period of 42 days
Gastrointestinal disorders Nausea	18.0% 9/50 • Number of events 10 • Adverse event data were collected over a period of 42 days	9.8% 5/51 • Number of events 5 • Adverse event data were collected over a period of 42 days
Gastrointestinal disorders Abdominal Pain Upper	14.0% 7/50 • Number of events 7 • Adverse event data were collected over a period of 42 days	11.8% 6/51 • Number of events 6 • Adverse event data were collected over a period of 42 days
Gastrointestinal disorders Constipation	6.0% 3/50 • Number of events 3 • Adverse event data were collected over a period of 42 days	11.8% 6/51 • Number of events 6 • Adverse event data were collected over a period of 42 days
Gastrointestinal disorders Dyspepsia	6.0% 3/50 • Number of events 3 • Adverse event data were collected over a period of 42 days	3.9% 2/51 • Number of events 2 • Adverse event data were collected over a period of 42 days
Musculoskeletal and connective tissue disorders Myalgia	20.0% 10/50 • Number of events 10 • Adverse event data were collected over a period of 42 days	11.8% 6/51 • Number of events 6 • Adverse event data were collected over a period of 42 days
Musculoskeletal and connective tissue disorders Back Pain	8.0% 4/50 • Number of events 4 • Adverse event data were collected over a period of 42 days	3.9% 2/51 • Number of events 2 • Adverse event data were collected over a period of 42 days
Musculoskeletal and connective tissue disorders Pain in Extremity	2.0% 1/50 • Number of events 1 • Adverse event data were collected over a period of 42 days	5.9% 3/51 • Number of events 3 • Adverse event data were collected over a period of 42 days
Nervous system disorders Headache	10.0% 5/50 • Number of events 7 • Adverse event data were collected over a period of 42 days	5.9% 3/51 • Number of events 3 • Adverse event data were collected over a period of 42 days
Nervous system disorders Restless Legs Syndrome	6.0% 3/50 • Number of events 4 • Adverse event data were collected over a period of 42 days	0.00% 0/51 • Adverse event data were collected over a period of 42 days
General disorders Pain	6.0% 3/50 • Number of events 3 • Adverse event data were collected over a period of 42 days	7.8% 4/51 • Number of events 4 • Adverse event data were collected over a period of 42 days
General disorders Fatigue	4.0% 2/50 • Number of events 2 • Adverse event data were collected over a period of 42 days	5.9% 3/51 • Number of events 3 • Adverse event data were collected over a period of 42 days
Vascular disorders Hypotension	8.0% 4/50 • Number of events 4 • Adverse event data were collected over a period of 42 days	2.0% 1/51 • Number of events 1 • Adverse event data were collected over a period of 42 days