Trial Outcomes & Findings for Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension) (NCT NCT02537574)
NCT ID: NCT02537574
Last Updated: 2019-03-06
Results Overview
Toleration to the injection was 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).
COMPLETED
PHASE3
380 participants
1 week
2019-03-06
Participant Flow
Adults with opioid use disorder who were voluntarily seeking treatment were eligible to enroll.
Two subjects were randomized, but did not receive study drug. Four subjects attempted enrollment at multiple sites. The data collected on these subjects during their second enrollment was excluded from the efficacy analyses.
Participant milestones
| Measure |
NTX/BUP
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Overall Study
STARTED
|
126
|
126
|
126
|
|
Overall Study
COMPLETED
|
27
|
23
|
18
|
|
Overall Study
NOT COMPLETED
|
99
|
103
|
108
|
Reasons for withdrawal
| Measure |
NTX/BUP
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
40
|
51
|
55
|
|
Overall Study
Noncompliance with study drug
|
0
|
1
|
1
|
|
Overall Study
Physician Decision
|
2
|
0
|
0
|
|
Overall Study
Protocol Violation
|
4
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
37
|
27
|
29
|
|
Overall Study
Lack of Efficacy
|
14
|
16
|
15
|
|
Overall Study
Duplicate Patient
|
1
|
0
|
0
|
|
Overall Study
Patient not Stable
|
0
|
1
|
0
|
|
Overall Study
Incarceration
|
0
|
1
|
0
|
|
Overall Study
Failed Naloxone Challenge
|
0
|
1
|
0
|
|
Overall Study
Transportation Issues
|
0
|
0
|
1
|
|
Overall Study
Subject did not want last Vivitrol Injec
|
0
|
0
|
1
|
|
Overall Study
Noncompliance with Protocol
|
0
|
0
|
1
|
Baseline Characteristics
Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension)
Baseline characteristics by cohort
| Measure |
NTX/BUP
n=126 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=126 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
Total
n=378 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
40 years
STANDARD_DEVIATION 10.68 • n=5 Participants
|
37.5 years
STANDARD_DEVIATION 9.21 • n=7 Participants
|
36.5 years
STANDARD_DEVIATION 10.38 • n=5 Participants
|
38.0 years
STANDARD_DEVIATION 10.19 • n=4 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
129 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
249 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
47 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
106 Participants
n=5 Participants
|
115 Participants
n=7 Participants
|
110 Participants
n=5 Participants
|
331 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
27 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
76 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
95 Participants
n=5 Participants
|
91 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
279 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
126 participants
n=5 Participants
|
126 participants
n=7 Participants
|
126 participants
n=5 Participants
|
378 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 1 weekPopulation: The Full Analysis Set (FAS) includes all subjects in the Safety Population (randomized subjects who received at least 1 dose of study drug), excluding the second enrollment of duplicate subjects (those subjects who enrolled multiple times in the same study).
Toleration to the injection was 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).
Outcome measures
| Measure |
NTX/BUP
n=124 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=124 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection
|
57 Participants
|
51 Participants
|
57 Participants
|
SECONDARY outcome
Timeframe: 1 weekPopulation: The Full Analysis Set (FAS) included all subjects in the Safety Population (randomized subjects who received at least 1 dose of study drug), excluding the second enrollment of duplicate subjects (those subjects who enrolled multiple times in the same study).
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
| Measure |
NTX/BUP
n=124 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=124 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Proportion of Days With COWS Peak Score of Less Than or Equal to 12 During the Treatment Period Prior to the VIVITROL Injection
|
5.0 Number of days
Standard Deviation 2.23
|
4.5 Number of days
Standard Deviation 2.50
|
5.4 Number of days
Standard Deviation 2.02
|
SECONDARY outcome
Timeframe: 1 weekPopulation: The Full Analysis Set (FAS) included all subjects in the Safety Population (randomized subjects who received at least 1 dose of study drug), excluding the second enrollment of duplicate subjects (those subjects who enrolled multiple times in the same study).
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
| Measure |
NTX/BUP
n=124 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=124 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Mean Peak COWS Score During Treatment Period Prior to VIVITROL Injection
|
7.39 score on a scale
Standard Deviation 3.726
|
7.78 score on a scale
Standard Deviation 3.981
|
6.11 score on a scale
Standard Deviation 3.044
|
SECONDARY outcome
Timeframe: The COWS was administered 4-6 times per day during the Treatment Period (Days 1-7)Population: All randomized subjects who received at least 1 dose of study drug and had 1 post-baseline COWS measurement.
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. To determine the daily AUC COWS score, a curve was generated by plotting the COWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC COWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC COWS score was then divided by the number of days with daily AUC COWS score during the treatment period. The AUC COWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Outcome measures
| Measure |
NTX/BUP
n=124 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=124 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Area Under the Curve (AUC) COWS Score During the Treatment Period Prior to VIVITROL Injection
|
955.7 Score on a scale
Standard Deviation 535.38
|
1004.8 Score on a scale
Standard Deviation 524.01
|
800.6 Score on a scale
Standard Deviation 403.01
|
SECONDARY outcome
Timeframe: 1 weekPopulation: 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 Visual Analog Scale (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". Subjects placed a vertical line on the scale to indicate their desire for opioids at that particular time.
Outcome measures
| Measure |
NTX/BUP
n=123 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=124 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=123 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Mean Score for Desire of Opioids During Treatment Period Prior to VIVITROL Injection
|
48.1 score on a scale
Standard Deviation 27.61
|
52.0 score on a scale
Standard Deviation 27.29
|
45.8 score on a scale
Standard Deviation 26.03
|
SECONDARY outcome
Timeframe: Up to 92 daysPopulation: The Safety Analysis Set was used to analyze this measure.
The number of subjects who experienced treatment-emergent Adverse Events.
Outcome measures
| Measure |
NTX/BUP
n=126 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=126 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Incidence of Adverse Effects
|
44 Participants
|
31 Participants
|
48 Participants
|
SECONDARY outcome
Timeframe: The SOWS was administered 4-6 times per day during the Treatment PeriodPopulation: All randomized subjects who received at least 1 dose of study drug and had at least 1 post-baseline SOWS measurement.
The Subjective Opiate Withdrawal Scale (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). To determine the daily AUC SOWS score, a curve was generated by plotting the SOWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC SOWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC SOWS score was then divided by the number of days with daily AUC SOWS score during the treatment period. The AUC SOWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Outcome measures
| Measure |
NTX/BUP
n=111 Participants
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=114 Participants
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=112 Participants
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Area Under the Curve SOWS Score During the Treatment Period Prior to the VIVITROL Injection
|
9038.5 Score on a scale
Standard Deviation 6800.60
|
10,262.5 Score on a scale
Standard Deviation 7294.10
|
9160.3 Score on a scale
Standard Deviation 6873.56
|
Adverse Events
NTX/BUP
NTX/PBO-B
PBO-N/PBO-B
Serious adverse events
| Measure |
NTX/BUP
n=126 participants at risk
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 participants at risk
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=126 participants at risk
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Psychiatric disorders
Panic Attack
|
0.79%
1/126 • Number of events 2 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
|
Social circumstances
Alcohol use
|
0.79%
1/126 • Number of events 2 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/126 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
0.79%
1/126 • Number of events 2 • Up to 92 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/126 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
0.79%
1/126 • Number of events 2 • Up to 92 days
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/126 • Up to 92 days
|
0.79%
1/126 • Number of events 1 • Up to 92 days
|
0.00%
0/126 • Up to 92 days
|
Other adverse events
| Measure |
NTX/BUP
n=126 participants at risk
Oral naltrexone + sublingual buprenorphine
NTX/BUP: Daily doses
|
NTX/PBO-B
n=126 participants at risk
Oral naltrexone + sublingual placebo
NTX/PBO-B: Daily doses
|
PBO-N/PBO-B
n=126 participants at risk
Oral placebo naltrexone + sublingual placebo buprenorphine
PBO-N/PBO-B: Daily doses
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
7/126 • Number of events 9 • Up to 92 days
|
4.8%
6/126 • Number of events 7 • Up to 92 days
|
7.1%
9/126 • Number of events 11 • Up to 92 days
|
|
Gastrointestinal disorders
Nausea
|
5.6%
7/126 • Number of events 8 • Up to 92 days
|
3.2%
4/126 • Number of events 4 • Up to 92 days
|
3.2%
4/126 • Number of events 5 • Up to 92 days
|
|
Psychiatric disorders
Anxiety
|
4.8%
6/126 • Number of events 6 • Up to 92 days
|
3.2%
4/126 • Number of events 4 • Up to 92 days
|
7.1%
9/126 • Number of events 10 • Up to 92 days
|
Additional Information
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