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

A Randomized, Open-label, Parallel-group Study to Evaluate the Efficacy of the Digital Therapeutic OXD01 (MODIA™) in Combination With Sublingual Buprenorphine/Naloxone for the Treatment of Opioid Use Disorder

This is an open-label, randomized, parallel-group multicenter study designed to evaluate the efficacy of the digital therapeutic OXD01 (MODIA) combined with sublingual buprenorphine/naloxone standard of care (SL BUP/NAL SOC) background therapy compared to SL BUP/NAL alone to change opioid use patterns in subjects with opioid use disorder (OUD).

Approximately 400 subjects will be randomized. The study will include a screening visit and a randomization visit, followed by 24 weeks of study treatment. Subjects will be scheduled for evaluation visits, which will include a urine drug screen (UDS) and a self-report of drug use, weekly during the first four weeks of treatment, then every other week from weeks 5 through 12, then monthly through week 25. Subjects will also return to the site for only a UDS and a self-report of drug use each week between the evaluation visits.

The primary objective of the study is to determine whether the combination of sublingual (SL) buprenorphine/naloxone (BUP/NAL) standard of care (SOC) background therapy and the digital therapeutic OXD01 is superior to SL BUP/NAL alone to reduce opioid use.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Device: OXD01 digital therapy; Other: Standard of Care

Detailed Description

Medication-assisted treatment, the current standard for opioid addiction, is the use of medications in combination with counseling and behavioral therapies to provide a "whole-patient" approach to the treatment of OUD. However, patients may not have optimal access to face-to-face clinical behavioral health services. Digital therapeutics can help bridge the gap between accessible services and optimal treatment of OUD, the primary goal of which is to reduce the use of opioids. OXD01 is a device-based digital therapeutic, designed to offer individuals diagnosed with OUD quality psychotherapy intervention based on cognitive behavioral therapy and motivational interviewing. This study is being conducted to determine the value of OXD01 when combined with medication to change opioid use patterns in subjects with OUD.

Note: No investigational product will be administered as part of this study.

• Study Type: Interventional
• Enrollment (Actual): 437
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35215
      • Parkway Medical Center
  • California
    • Oceanside, California, United States, 92054
      • North County Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92120
      • Wetlin Research Associates, Inc
  • Florida
    • Pembroke Pines, Florida, United States, 33024
      • Humanity Clinical Research
  • Illinois
    • Glen Carbon, Illinois, United States, 62034
      • Southern Illinois Associates LLC
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Otrimed Clinical Research
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • Patient First Medical Clinic
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
  • New York
    • Bronx, New York, United States, 10466
      • Dr. Vando Medical Services PC
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research Center
    • West Chester, Ohio, United States, 45069
      • CincyScience
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pahl Pharmaceuticals Professions
  • Pennsylvania
    • Haverford, Pennsylvania, United States, 19041
      • Thalia Medical Center
    • Kingston, Pennsylvania, United States, 18704
      • MD Medical Management
    • Philadelphia, Pennsylvania, United States, 19116
      • Medically Assisted Recovery Service
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Institute of Addiction Medicine
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female 18 - 65 years of age at the screening visit, fluent in English and able to read, comprehend, and willingly sign the informed consent form (ICF).
2. Voluntarily seeking treatment for OUD.
3. In the judgment of the Investigator has the appropriate hearing, vision, manual dexterity, ability to understand instructions, and ability to use and understand internet-based applications.
4. Currently meets the criteria for moderate or severe opioid use disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-V (Appendix B).
5. Has a positive UDS for opioids at screening that is consistent with their drug use history.
6. In good health as determined by lack of clinically significant abnormalities in health assessments performed at screening.
7. Agrees not to take any buprenorphine products other than those prescribed by the Investigator during participation in the study, and agrees to use OXD01 as directed if randomized to that treatment group.
8. Completed SL BUP/NAL induction, with physical withdrawal symptoms reduced so the subject is able to fulling participate in OXD01 training, if randomized to that treatment group, and is no greater than 14 days from the first dose of SL BUP/NAL induction.

Exclusion Criteria:

• 1. Unwilling or unable to comply with the requirements of the protocol or are in a situation or condition that, in the opinion of an Investigator, may interfere with participation in the study (e.g., does not have reliable internet access).

  2. History of allergy or sensitivity to naloxone, buprenorphine or other opioids, or history of any drug hypersensitivity or intolerance which, in the opinion of an Investigator, would compromise the safety of the subject.

  3. Used an investigational drug within 30 days or 5 half-lives (whichever is greater) prior to randomization.

  4. Received prescribed medication-assisted treatment with buprenorphine, methadone, or naltrexone for opioid use disorder within 14 days prior to screening.

  5. Past or present diseases that, judged by an Investigator and based on available medical history/records, may jeopardize the safety of the subject or impact the validity of the study results.

  6. Tongue piercing, or piercings in the mouth or oral deformities that may affect sublingual absorption, in the opinion of an Investigator.

  7. Hospitalization for a psychiatric disorder in the past 30 days, not including inpatient treatment for drug rehabilitation.

  8. Schizophrenia, or other serious mental illness defined as a mental, behavioral, or emotional disorder resulting in serious functional impairment which substantially interferes with or limits participation in the study.

  9. A Quick Inventory of Depression Symptoms - Self-Report (QIDS-SR, Appendix C) score ≥ 16 (severe depression) or a rating of 2 or 3 for question 12 (Thoughts of Death or Suicide) at screening.

  10. A current diagnosis, other than opioid use disorder, requiring chronic opioid treatment.

  11. Chronic pain that is unremitting or unstable. 12. Current DSM-V diagnosis of moderate to severe substance use disorder for psychoactive substances other than opioids, caffeine, marijuana, or nicotine.

  13. Requires current use of medications that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4 (Section 4.3.1).

  14. Any pending legal action that could affect participation or compliance in the trial.

  15. Is an employee of the Investigator or the trial site, with direct involvement in the proposed trial or other trials under the direction of the Investigator or trial site, or is a family member of the Investigator or an employee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sublingual buprenorphine/naloxone (SL BUP/NAL) standard of care (SOC) background therapy; Standard of care. 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.	Other: Standard of Care; Sublingual buprenorphine/naloxone Medication-assisted treatment, the current standard for opioid addiction; the use of medications in combination with counseling
Experimental: Sublingual buprenorphine/naloxone (SL BUP/NAL) + OXD01; Standard of care + OXD01 (digital therapy). 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.	Device: OXD01 digital therapy; OXD01 digital therapy, 1-2 times per week 15-30 minutes each time.; Other: Standard of Care; Sublingual buprenorphine/naloxone Medication-assisted treatment, the current standard for opioid addiction; the use of medications in combination with counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success Rate	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.	Week 6 to Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Response Rate	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.	Week 6 to Week 25
Cumulative Response Rate - Drug Test for Illicit Use of Opioids	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.	Week 6 to Week 25
Cumulative Response Rate - Self-reports of Illicit Use of Opioids	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.	Week 6 to Week 25
Percentage of Subjects Abstinent	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.	Week 25
Proportion of Subjects Completing the Study	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.	Week 25
Global Clinical Impression - Severity	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; = Normal, not at all ill; = Borderline ill; = Mildly ill; = Moderately ill; = Markedly ill; = Severely ill; = Among the most extremely ill subjects	Week 13 and Week 25
Clinical Global Impression - Improvement	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; = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse	Week 13 and Week 25
Opioid Cravings - Change From Baseline	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.	Day 1 (baseline) and Weeks 5, 9, 13, 17, 21 and 25.
Cumulative Response Rate - Illicit Non-opioid Drugs of Abuse	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.	Week 6 to Week 25
Resource Use - Number of Hospitalizations	Number of subject hospitalizations weeks 1-25.	Weeks 1-25
Resume Productive Activity	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.	Week 25
Resource Use - Emergency Department Visits	Number of subject emergency department visits weeks 1-25.	Weeks 1-25
Overdose Events	Overdose events	Weeks 1-25

Collaborators and Investigators

• Sponsor: Orexo AB
• Investigators: Study Director: David Capano, PharmD, Orexo US, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): May 10, 2023

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: cognitive behavioral therapy (CBT); digital therapy
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Substance-Related Disorders
• Other Study ID Numbers: OXD01-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No