A Phase III, Randomized, Double-Blind, Placebo-Controlled, Enriched-Enrollment Withdrawal, Multicenter Study to Evaluate the Efficacy and Safety of a Long-Acting Subcutaneous Injectable Depot of Buprenorphine (CAM2038) in Subjects With Moderate to Severe Chronic Low Back Pain Currently Treated With Daily Opioids
Overview
- Phase
- Phase 3
- Intervention
- buprenorphine
- Conditions
- Chronic Lower Back Pain
- Sponsor
- Braeburn Pharmaceuticals
- Enrollment
- 1053
- Locations
- 69
- Primary Endpoint
- Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase.
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase III, placebo-controlled, multicenter study with an enriched-enrollment withdrawal (EEW) design to evaluate the efficacy and safety of CAM2038 in opioid-experienced subjects with moderate to severe CLBP that requires continuous, around-the-clock (ATC) opioid treatment ≥ 40 mg morphine equivalent dose (MED). The study includes 5 phases: A Screening Phase (up to 2 weeks), a Transition Phase (up to 2 weeks), an Open-Label Titration Phase (up to 10 weeks), a Double-Blind Treatment Phase including a Final Study Visit (12 weeks), and a Follow-up Phase (4 weeks). The overall duration of participation in the core phase of the study (randomized Double-Blind Phase) is up to 30 weeks, from the Screening Phase through the Follow-up Phase. Subjects who complete the Double-Blind Treatment Study Phase will be offered an opportunity to continue treatment in an open label safety extension for up to 60 weeks. Additional subjects may be recruited to open label safety extension to meet the goal of 100 subjects with 60 weeks of treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent provided prior to the conduct of any study-related procedures.
- •Male or non-pregnant, non-lactating female subject, greater than or equal to 18 years old.
- •Body mass index (BMI) between 18 and 38 kg/m2, inclusive.
- •Treated with daily opioids for moderate to severe CLBP for a minimum of 3 months prior to Screening.
- •On a stable dose of ≥40 mg/day of oral morphine or MED during the 14 days prior to Screening.
- •Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg.
- •Female subject of childbearing potential who is willing to use a reliable method of contraception during the entire study (Screening Visit to final Follow-up). To be considered not of childbearing potential, female subjects must be surgically sterile (hysterectomy or bilateral oophorectomy, or bilateral tubal ligation with surgery at least 6 weeks before Screening).
- •Male subject who is willing to use reliable contraception
- •Willing and able to comply with all study procedures and requirements.
Exclusion Criteria
- •Positive for hepatitis B surface antigen, hepatitis C viral RNA, or antibodies to human immunodeficiency virus (HIV).
- •Clinically significant symptoms, medical conditions, or other circumstances which, in the opinion of the investigator, would preclude compliance with the protocol, adequate cooperation in the study, or obtaining informed consent, or may prevent the subject from safely participating in the study, including the following:
- •Severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, biliary tract disease, severe hepatic insufficiency, or planned surgery.
- •Bipolar disorder
- •Current diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-defined moderate to severe substance use disorder (including alcohol), other than caffeine or nicotine.
- •Female subject planning to become pregnant during the study.
- •Surgical procedure(s) for CLBP within 6 months prior to Screening.
- •Concomitant disease(s) that could prolong the QTcF interval, such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, Long QT Syndrome, or family history of Long QT Syndrome.
- •QTcF \>450 ms for males and \>470 ms for females, or clinically significant electrocardiogram (ECG) abnormality at Screening, at the investigator's discretion.
- •Currently taking medications that have the potential to prolong the QTcF interval or may require such medications during the course of the study (Appendix 1) and has clinically significant abnormalities on screening ECG readings, as determined by the investigator.
Arms & Interventions
CAM2038
CAM2038 50 mg/mL q1w at doses of 8 mg, 12 mg, 16 mg, 24 mg, or 32 mg. CAM2038 356 mg/mL q4w at doses of 64 mg, 96 mg, or 128 mg.
Intervention: buprenorphine
Placebo
CAM2038 placebo injections
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase.
Time Frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 0 being no pain and 10 being the worst pain.
Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase.
Time Frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase based on the 11-Point numerical rating scale with 10 being the worst pain. Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects.
Secondary Outcomes
- Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain.(12 weeks- from randomization baseline to 12 weeks after randomization)
- Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase.(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy.(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Number of Subjects Discontinued Due to Loss of Efficacy(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale(12 weeks- from baseline (randomization) to 12 weeks after randomization)
- Summary of Rescue Medication Usage- Double-Blind Phase.(12 weeks- from randomization baseline to 12 weeks after randomization)
- Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase.(12 weeks- from randomization baseline to 12 weeks after randomization)
- Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score.(12 weeks- from randomization baseline to 12 weeks after randomization)
- Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score(23 weeks- from baseline to 12 weeks after randomization)
- Summary of Rescue Medication Usage-Open Label Phase(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)
- Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase(48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).)