Trial Outcomes & Findings for OXD01 in Combination With Sublingual Buprenorphine/Naloxone for Treatment of Opioid Use Disorder (NCT NCT04948307)

NCT ID: NCT04948307

Last Updated: 2025-06-27

Results Overview

The primary objective was to determine whether the combination of sublingual buprenorphine/naloxone (SL BUP/NAL) and OXD01 was superior to SL BUP/NAL alone to reduce opioid use, measured by the treatment success rate. Treatment success was defined as the subject having \>/=80% of urine drug tests negative for opioids plus \>/=80% of self-reports negative for illicit opioid use from Week 6 to Week 25. Each subject was evaluated as a success or failure for this metric. The percentage of subjects in each group demonstrating treatment success was tested using the Chi-square test. If the subject withdrew from the study, the urine drug tests and self-reports for illicit opioid use for all visits after withdrawal were imputed as positive. If the subject completed the study with missing visits, the missing urine drug tests and self-reports for illicit opioids were imputed as positive.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 437 participants
• Primary outcome timeframe: Week 6 to Week 25
• Results posted on: 2025-06-27

Participant Flow

Patients were recruited from 30 June 2021 to 12 April 2023 at 36 outpatient sites in the United States.

Screening All Consented Subjects n (%) Screened: 672 Screen failure: 235 ( 35.0) Primary reason for screen failure due to COVID-19: 2 ( 0.3) Primary reason for screen failure: Failure to meet randomization criteria - 134 ( 19.9) Lost to follow-up - 63 ( 9.4) Withdrawal by subject - 23 ( 3.4) Adverse event - 2 (0.3) Physician decision - 1 (0.1) Other - 11 (1.6) Missing - 1 (0.1)

Participant milestones

Measure	SL BUP/NAL SOC Background Therapy Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Overall Study STARTED	218	219
Overall Study COMPLETED	120	114
Overall Study NOT COMPLETED	98	105

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

OXD01 in Combination With Sublingual Buprenorphine/Naloxone for Treatment of Opioid Use Disorder

Baseline characteristics by cohort

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	Total n=437 Participants Total of all reporting groups
Age, Continuous	39.9 years STANDARD_DEVIATION 10.41 • n=5 Participants	41.9 years STANDARD_DEVIATION 10.63 • n=7 Participants	40.9 years STANDARD_DEVIATION 010.56 • n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	111 Participants n=7 Participants	201 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants	108 Participants n=7 Participants	236 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	37 Participants n=5 Participants	41 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	171 Participants n=5 Participants	167 Participants n=7 Participants	338 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	30 Participants n=5 Participants	25 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) White	180 Participants n=5 Participants	191 Participants n=7 Participants	371 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	218 participants n=5 Participants	219 participants n=7 Participants	437 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 6 to Week 25

Population: Full Analysis Population

The primary objective was to determine whether the combination of sublingual buprenorphine/naloxone (SL BUP/NAL) and OXD01 was superior to SL BUP/NAL alone to reduce opioid use, measured by the treatment success rate. Treatment success was defined as the subject having >/=80% of urine drug tests negative for opioids plus >/=80% of self-reports negative for illicit opioid use from Week 6 to Week 25. Each subject was evaluated as a success or failure for this metric. The percentage of subjects in each group demonstrating treatment success was tested using the Chi-square test.

If the subject withdrew from the study, the urine drug tests and self-reports for illicit opioid use for all visits after withdrawal were imputed as positive. If the subject completed the study with missing visits, the missing urine drug tests and self-reports for illicit opioids were imputed as positive.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Treatment Success Rate	70 Participants	67 Participants

SECONDARY outcome

Timeframe: Week 6 to Week 25

Population: Full analysis population

The cumulative response rate was calculated from Week 6 to Week 25 of treatment. Response was defined as the presence of both a negative urine drug test for opioids and a negative self-report for illicit use of opioids at a study visit. The cumulative response rate from Week 6 to Week 25 is calculated by dividing the number of responses from Week 6 to Week 25 by the total number of visits (20), and then multiplying by 100%. The outcome is expressed as the mean percent response in each treatment group. The Kolmogorov-Smirnov method was used to compare the treatment groups.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Cumulative Response Rate	41.9 percent of visits with a response Standard Deviation 40.83	42.2 percent of visits with a response Standard Deviation 38.61

SECONDARY outcome

Timeframe: Week 6 to Week 25

Population: Full analysis population

The cumulative response rate for the illicit use of opioids was calculated from Week 6 to Week 25 of treatment. Response was defined as the presence of a negative urine drug test for opioids at a study visit. The cumulative response rate from Week 6 to Week 25 is calculated by dividing the number of responses from Week 6 to Week 25 by the total number of visits (20), and then multiplying by 100%. The outcome is expressed as the mean percent response in each treatment group. The Kolmogorov-Smirnov method was used to compare the treatment groups.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Cumulative Response Rate - Drug Test for Illicit Use of Opioids	43.6 percent of visits with a response Standard Deviation 41.50	45.0 percent of visits with a response Standard Deviation 39.82

SECONDARY outcome

Timeframe: Week 6 to Week 25

Population: Full analysis population

The cumulative response rate was calculated from Week 6 to Week 25 of treatment. Response was defined as the presence of a negative self-report for illicit use of opioids at a study visit. The cumulative response rate from Week 6 to Week 25 is calculated by dividing the number of responses from Week 6 to Week 25 by the total number of visits (20) and then multiplying by 100%. The outcome is expressed as the mean percent response in each treatment group. The Kolmogorov-Smirnov method was used to compare the treatment groups.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Cumulative Response Rate - Self-reports of Illicit Use of Opioids	51.9 percent of visits with a response Standard Deviation 41.25	51.3 percent of visits with a response Standard Deviation 39.40

SECONDARY outcome

Timeframe: Week 25

Population: Full analysis population

Abstinence is defined as a subject having urine drug tests negative for opioids as well as self-reports negative for illicit use of opioids at Week 25. Positive urine drug tests or positive timeline followback (TLFB) qualified as not abstinent. Each subject was scored as abstinent or non-abstinent and the groups were compared using a chi-squared test.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Percentage of Subjects Abstinent Abstinent at Week 25	84 Participants	78 Participants
Percentage of Subjects Abstinent Not abstinent at Week 25	134 Participants	141 Participants

SECONDARY outcome

Timeframe: Week 25

Population: Full analysis population

A study completer was defined as a subject who completed either the urine drug screen (UDS) or the self-report assessment at the Week 25 visit. The endpoint completion rate differs from the disposition completion rate because the disposition rate used the study completion definition instead of the UDS or self-report assessment at the Week 25 visit.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Proportion of Subjects Completing the Study	137 Participants	127 Participants

SECONDARY outcome

Timeframe: Week 13 and Week 25

Population: Full analysis population

Clinical global Impression - severity - The severity of opioid dependence was assessed at Week 13 and Week 25 using the following assessment scale:

Considering your total clinical experience with this particular population, how mentally ill is the subject at this time?

0 = Not assessed

1. = Normal, not at all ill

2. = Borderline ill

3. = Mildly ill

4. = Moderately ill

5. = Markedly ill

6. = Severely ill

7. = Among the most extremely ill subjects

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Global Clinical Impression - Severity Week 13	2.3 score on a scale Standard Deviation 1.18	2.3 score on a scale Standard Deviation 1.21
Global Clinical Impression - Severity Week 25	2.2 score on a scale Standard Deviation 1.15	2.2 score on a scale Standard Deviation 1.23

SECONDARY outcome

Timeframe: Week 13 and Week 25

Population: Full analysis population

Clinical global impression - improvement - Improvement in severity of opioid dependence from baseline (study Day 1) was assessed by the Investigator at the visit on Week 13 and Week 25 using the following assessment scale:

Rate total improvement whether or not, in your judgement, it is due entirely to drug treatment. Compared to his or her condition at admission to the project, how much has the subject changed?

0 = Not assessed

1. = Very much improved

2. = Much improved

3. = Minimally improved

4. = No change

5. = Minimally worse

6. = Much worse

7. = Very much worse

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Clinical Global Impression - Improvement Week 13	2.5 score on a scale Standard Deviation 1.02	2.5 score on a scale Standard Deviation 0.99
Clinical Global Impression - Improvement Week 25	2.0 score on a scale Standard Deviation 1.07	2.2 score on a scale Standard Deviation 1.19

SECONDARY outcome

Timeframe: Day 1 (baseline) and Weeks 5, 9, 13, 17, 21 and 25.

Population: Full analysis population

Cravings for opioids were assessed by the subject through the use of a visual analog scale (VAS), where 0 mm represents "no cravings" and 100 mm represents "the most intensive craving I have ever had". The baseline craving VAS assessment was collected on study Day 1 and subsequent assessments were collected at the visit on Weeks 5, 9, 13, 17, 21, and 25.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Opioid Cravings - Change From Baseline Day 1 (baseline)	34.1 score on a scale Standard Deviation 29.44	32.4 score on a scale Standard Deviation 29.83
Opioid Cravings - Change From Baseline Week 5	-7.6 score on a scale Standard Deviation 23.80	-6.2 score on a scale Standard Deviation 25.26
Opioid Cravings - Change From Baseline Week 9	-3.8 score on a scale Standard Deviation 30.02	-7.2 score on a scale Standard Deviation 26.87
Opioid Cravings - Change From Baseline Week 13	-9.0 score on a scale Standard Deviation 26.58	-9.6 score on a scale Standard Deviation 28.32
Opioid Cravings - Change From Baseline Week 17	-6.3 score on a scale Standard Deviation 25.89	-9.2 score on a scale Standard Deviation 28.46
Opioid Cravings - Change From Baseline Week 21	-9.0 score on a scale Standard Deviation 25.90	-11.8 score on a scale Standard Deviation 29.49
Opioid Cravings - Change From Baseline Week 25	-12.0 score on a scale Standard Deviation 26.95	-16.6 score on a scale Standard Deviation 32.13

SECONDARY outcome

Timeframe: Week 6 to Week 25

Population: Full analysis population

The cumulative response rate was calculated from Week 6 to Week 25 of treatment. Response was defined as the presence of both a negative urine drug test for opioids and a negative self-report for illicit use of non-opioid drugs of abuse at a study visit. The cumulative response rate from Week 6 to Week 25 is calculated by dividing the number of responses from Week 6 to Week 25 by the total number of visits (20) and then multiplying by 100%. The outcome is expressed as the mean percent response in each treatment group. The Kolmogorov-Smirnov method was used to compare the treatment groups.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Cumulative Response Rate - Illicit Non-opioid Drugs of Abuse	39.31 percent of visits with a response Standard Deviation 39.879	40.82 percent of visits with a response Standard Deviation 37.625

SECONDARY outcome

Timeframe: Weeks 1-25

Population: Full analysis population

Number of subject hospitalizations weeks 1-25.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Resource Use - Number of Hospitalizations	0.0 hospitalizations Standard Deviation 0.19	0.0 hospitalizations Standard Deviation 0.22

SECONDARY outcome

Timeframe: Week 25

Population: Full analysis population

Subjects were asked if they were able to resume work, school, or other productive activities. The possible responses were Yes, No, and No Change. Only subjects with non-missing data in each group were included in the analysis.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=179 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=165 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Resume Productive Activity Yes	97 Participants	107 Participants
Resume Productive Activity No	6 Participants	4 Participants
Resume Productive Activity No change	76 Participants	54 Participants

SECONDARY outcome

Timeframe: Weeks 1-25

Population: Full analysis population

Number of subject emergency department visits weeks 1-25.

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Resource Use - Emergency Department Visits	0.1 number of emergency department visits Standard Deviation 0.49	0.2 number of emergency department visits Standard Deviation 0.55

SECONDARY outcome

Timeframe: Weeks 1-25

Population: Full analysis population

Overdose events

Outcome measures

Measure	SL BUP/NAL SOC Background Therapy n=218 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 Participants Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Overdose Events	0.0 overdose events Standard Deviation 0.23	0.0 overdose events Standard Deviation 0.13

Adverse Events

SL BUP/NAL SOC Background Therapy

Serious events: 9 serious events

Other events: 41 other events

Deaths: 1 deaths

SL BUP/NAL SOC Background Therapy + OXD01

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	SL BUP/NAL SOC Background Therapy n=218 participants at risk Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 participants at risk Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Infections and infestations Pneumonia	0.46% 1/218 • Number of events 1 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Infections and infestations Cellulitis	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Infections and infestations Osteomyelitis	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Injury, poisoning and procedural complications Accidental overdose	0.92% 2/218 • Number of events 2 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Infections and infestations Bacterial sepsis	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Injury, poisoning and procedural complications Gun shot wound	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Respiratory, thoracic and mediastinal disorders Asthma	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Psychiatric disorders Agitation	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Psychiatric disorders Suicidal ideation	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Cardiac disorders Cardiac failure	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks
Gastrointestinal disorders Colitis	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
General disorders Drug withdrawal syndrome	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Nervous system disorders Status epilepticus	0.46% 1/218 • Number of events 1 • 25 weeks	0.00% 0/219 • 25 weeks
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/218 • 25 weeks	0.46% 1/219 • Number of events 1 • 25 weeks

Other adverse events

Measure	SL BUP/NAL SOC Background Therapy n=218 participants at risk Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.	SL BUP/NAL SOC Background Therapy + OXD01 n=219 participants at risk Sublingual buprenorphine/naloxone titrated to a maintenance dose that suppresses withdrawal signs and symptoms plus OXD01 digital therapy, accessed for 15-30 minutes, 1-2 times per week Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice.
Psychiatric disorders Anxiety	3.2% 7/218 • Number of events 7 • 25 weeks	0.91% 2/219 • Number of events 2 • 25 weeks
Nervous system disorders Headache	0.92% 2/218 • Number of events 2 • 25 weeks	2.3% 5/219 • Number of events 6 • 25 weeks
Infections and infestations COVID-19	4.6% 10/218 • Number of events 10 • 25 weeks	5.5% 12/219 • Number of events 13 • 25 weeks
Infections and infestations Upper respiratory tract infection	3.2% 7/218 • Number of events 7 • 25 weeks	0.91% 2/219 • Number of events 2 • 25 weeks
Infections and infestations Urinary tract infection	2.3% 5/218 • Number of events 5 • 25 weeks	0.91% 2/219 • Number of events 4 • 25 weeks
Gastrointestinal disorders Nausea	2.8% 6/218 • Number of events 6 • 25 weeks	3.2% 7/219 • Number of events 7 • 25 weeks
Gastrointestinal disorders Constipation	2.3% 5/218 • Number of events 5 • 25 weeks	2.3% 5/219 • Number of events 5 • 25 weeks
Gastrointestinal disorders Diarrhea	1.8% 4/218 • Number of events 4 • 25 weeks	2.3% 5/219 • Number of events 5 • 25 weeks

Additional Information

David Capano

Orexo US, Inc.

Phone: 9085079909

Email: david.capano@orexo.com

Results disclosure agreements

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