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

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

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.

Study Overview

• Status: Completed
• Conditions: Opioid Dependence, on Agonist Therapy
• Intervention / Treatment: Drug: Higher bioavailability BNX sublingual tablets

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 668
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Jefferson County, Alabama, United States
    • Marion County, Alabama, United States
    • Winston County, Alabama, United States
  • Arizona
    • Maricopa County, Arizona, United States
  • California
    • Los Angeles County, California, United States
    • San Diego County, California, United States
  • Florida
    • Broward County, Florida, United States
    • Columbia County, Florida, United States
    • Duval County, Florida, United States
    • Jacksonville metropolitan area, Florida, United States
    • Miami-Dade County, Florida, United States
    • Orlando metropolitan area, Florida, United States
    • Osceola County, Florida, United States
    • Palm Beach County, Florida, United States
  • Georgia
    • DeKalb County, Georgia, United States
  • Illinois
    • Chicago metropolitan area, Illinois, United States
  • Maryland
    • Baltimore County, Maryland, United States
  • Massachusetts
    • Bristol County, Massachusetts, United States
  • Mississippi
    • Rankin County, Mississippi, United States
  • Missouri
    • St. Louis metropolitan area, Missouri, United States
  • New Jersey
    • Warren County, New Jersey, United States
  • Oklahoma
    • Oklahoma County, Oklahoma, United States
  • Oregon
    • Portland metropolitan area, Oregon, United States
  • Pennsylvania
    • Delaware County, Pennsylvania, United States
    • Philadelphia County, Pennsylvania, United States
  • South Carolina
    • Charleston County, South Carolina, United States
  • Utah
    • Salt Lake County, Utah, United States
  • Washington
    • Benton County, Washington, United States

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label BNX sublingual tablets; 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; Once daily, open-label treatment with higher bioavailability BNX sublingual tablets for 24 weeks; Other Names: OX219; Zubsolv; Buprenorphine/naloxone sublingual tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Orexo AB
• Collaborators: Worldwide Clinical Trials
• Investigators: Principal Investigator: Kent Hoffman, TRY Research, 406 Lake Howell Road, Maitland, Florida 32751

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 9, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Estimate): October 28, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Opioid, Dependence, agonist, Buprenorphine, Naloxone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination
• Other Study ID Numbers: OX219-008