Multi-Center, Open-Label, 24-Week Study of OX219 Safety and Efficacy for Maintenance Treatment of Opioid Dependence

Study Overview
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Brief Summary
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The purpose of this study was to assess safety, efficacy, and treatment retention following extended treatment with OX219, a higher-bioavailability buprenorphine/naloxone (BNX) sublingual tablet formulation in opioid-dependent patients who completed 1 of 2 primary efficacy and safety studies of OX219.

Detailed Description
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This was a multicenter, open-label, uncontrolled, single-arm, 24-week, extension study to assess safety, efficacy, and treatment retention during maintenance treatment. Eligible patients had completed 1 of 2 primary efficacy and safety studies of the higher-bioavailability BNX sublingual tablet formulation (primary study OX219-006 [NCT01908842] or OX219-007 [NCT01848054]). The total duration of study treatment was 24 weeks.

Official Title
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A Multi-center, Open-Label, 24-Week, Follow-Up Study to Assess Safety, Efficacy, and Treatment Adherence For Maintenance Treatment of Opioid Dependence With OX219

Conditions
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Opioid Dependence, on Agonist Therapy

Intervention / Treatment
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* Drug: Higher bioavailability BNX sublingual tablets


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Signed informed consent form. Completion of 1 of 2 primary efficacy safety studies of BNX sublingual tablets (OX219-006 or OX219-007). Female patients of child bearing potential who used a reliable method of contraception (hormonal, condom with spermicide, intrauterine device) during the previous OX219-006 or OX219-007 study and continue to use it for the OX219-008 study. Females who are not of child-bearing potential who are either surgically sterile (by hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation), or postmenopausal, as defined by being at least 50 years of age and having had an absence of menses for at least 2 years, were also eligible. Exclusion criteria Females who are pregnant (positive pregnancy test result) or lactating, or planning to become pregnant during the study. Participants who are unwilling or unable to comply with the requirements of the protocol (eg, pending incarceration) or are in a situation or condition that, in the opinion of the investigator, may interfere with participation in the study. Participants who are participating in any other clinical study in which medication(s) are being delivered or who had used an investigational drug or device within the last 30 days. Participants with any known allergy or sensitivity or intolerance to buprenorphine, naloxone, or any related drug, or history of any drug hypersensitivity or intolerance that, in the opinion of the investigator, would compromise the safety of the subject or the study. Participant with a contra-indicated serious medical condition. Participants who are at suicidal risk as determined by any of the following: a history of suicidal ideation ≤ 3 months prior to baseline with a score of 4 (intent to act) or 5 (specified plan and intent) on the Columbia Suicide Severity Risk Scale (C-SSRS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label BNX sublingual tablets<br>Weeks 1-24: Higher bioavailability BNX sublingual tablets (open-label) were titrated at doses ranging from 5.7/1.4 mg to 17.1/4.2 mg, to a dose that relieved opioid cravings and withdrawal symptoms with minimal side effects. | Drug: Higher bioavailability BNX sublingual tablets<br>* Once daily, open-label treatment with higher bioavailability BNX sublingual tablets for 24 weeks<br>* Other names: Buprenorphine/naloxone sublingual tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Reporting Treatment-Emergent Adverse Events | Number of patients reporting treatment-emergent adverse events during open-label, extension treatment with higher bioavailability BNX sublingual tablets | Day 1 through week 24 | 
| Number of Patients Reporting Treatment-Related, Treatment-Emergent Adverse Events | Treatment-emergent adverse events considered related to treatment with the higher bioavailability BNX sublingual tablets | Day 1 through week 24 | 
| Number of Patients Reporting Treatment-Emergent Serious Adverse Events | Patients reporting treatment-emergent serious adverse events considered either related or not related to treatment with the higher bioavailability BNX sublingual tablets | Day 1 throught week 24 | 
| Number of Patient Discontinuations Due to Treatment-Emergent Adverse Events | Study discontinuations due to treatment-emergent adverse events that occurred during treatment with bioavailability BNX sublingual tablets | Day 1 through week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in Treatment in the Safety Population | Retention in treatment by visit in the safety population at weeks 4, 8, 12, 16, 20, and 24, defined as the number of patients receiving treatment on the day of the visit (± 5 days for each visit) | Treatment retention was assessed at weeks 4, 8, 12, 16, 20, and 24 | 
| Mean Change From Primary Study Baseline (OX219-006 or OX219-007) in Clinical Opioid Withdrawal Scale (COWS) Score | Mean change from primary study baseline in COWS total scores during the 24-week open-label, extension study; COWS scores range from 0 to 48, with a lower score being more favorable; study endpoint was defined as the last post-baseline value recorded for COWS | Prior to dosing on day 1, at weeks 4, 8,12,16, 20, 24, and at study endpoint | 
| Mean Change From Primary Study Baseline (OX219-006 or OX219-007) in Subjective Opioid Withdrawal Scale (SOWS) Score | Mean change from primary study baseline in SOWS total scores during the 24-week open-label, extension study; SOWS scores range from 0 to 64, with a lower score being more favorable; study endpoint was defined as the last post-baseline value recorded for SOWS | Prior to dosing on day 1, at weeks 4, 8,12,16, 20, and 24, and at study endpoint | 
| Mean Change From Primary Study Baseline (OX219-006 and OX219-007) in Visual Analog Scale (VAS) Craving Scores | Mean change from primary study baseline in VAS craving scores during the 24-week open-label, extension study; VAS craving scores range from 0 (no cravings) to 100 mm (most intense craving I have ever had); study endpoint was defined as the last post-baseline value recorded for VAS craving | Prior to dosing on day 1, at weeks 4, 8, 12, 16, 20, and 24, and at study endpoint | 
| Percent Change From Primary Study Baseline (OX219-006 or OX219-007) for Question 1 of the Work Productivity/Activity Impairment: 6-Question Specific Health Problem Questionnaire (WPAI:SHP) | Question 1 of the WPAI:SHP asks patients to provide a yes or no response to the question Are you employed?; The percentage of patients employed at the end of the 24-week open-label, extension study was calculated by subtracting the percentage of previously employed patients not employed at study end from the percentage of previously unemployed patients who were employed by study end | Study Endpoint | 
| Mean Change From Primary Study Baseline (OX219-006 or OX219-007) for Questions 2-4 of the WPAI:SHP | Mean change from primary study baseline to week 24 of the open-label, extension study for questions 2-4 of the WPAI:SHP; Question 2: During the past 7 days, how many hours did you miss from work because of problems associated with your opioid dependence?; Question 3: During the past 7 days, how many hours did you miss from work because of any other reason, such as vacation, holidays, time off to participate in this study?; Question 4: During the past 7 days, how many hours did you actually work? | Week 24 | 
| Mean Change From Primary Study Baseline (OX219-006 or OX219-007) for Questions 5-6 of the WPAI:SHP | Mean change from primary study baseline to week 24 of the open-label extension study for questions 5-6 of the WPAI:SHP; Question 5: During the past 7 days, how much did your opioid dependence affect your productivity while you were working?; Question 6: During the past 7 days, how much did your opioid dependence affect your ability to do regular daily activities, other than work at a job?; Questions 5 and 6 of the WPAI:SHP are scored on an 11-point scale (0 = problem had no effect; 10 = problem completely prevented me from doing my work/daily activities) | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid, Dependence, agonist, Buprenorphine, Naloxone