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Buprenorphine (CAM2038) in Subjects With a Recent History of Moderate to Severe Chronic Low Back Pain (CAM2038)

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ClinicalTrials.gov Identifier: NCT02946073
Recruitment Status : Active, not recruiting
First Posted : October 26, 2016
Last Update Posted : July 18, 2018
Sponsor:
Collaborators:
Medpace, Inc.
Camurus AB
Information provided by (Responsible Party):
Braeburn Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 7, 2016
First Posted Date  ICMJE October 26, 2016
Last Update Posted Date July 18, 2018
Actual Study Start Date  ICMJE September 2016
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
Change from baseline in Weekly Average of (Daily) Average Pain Intensity and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 10 being the worst pain. [ Time Frame: 12 weeks ]
Change from baseline in WAAPI and the primary timepoint will be Week 12 of the Double-Blind Phase.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
Difference of worst pain intensity scores from baseline to week 12 to determine the efficacy of CAM2038 once-weekly and CAM2038 once-monthly compared to placebo [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT02946073 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • 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. [ Time Frame: 12 weeks ]
  • Percentage of subjects with a 30% or greater decrease in API from baseline to Week 12 of the Double-Blind Phase. [ Time Frame: 12 weeks ]
  • Rescue medication usage (total dose) during the Double-Blind Phase. [ Time Frame: 12 weeks ]
  • Rescue medication usage (number of days used) during the Double-Blind Phase. [ Time Frame: 12 weeks ]
  • Change from baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level self-report questionaire score. [ Time Frame: 12 weeks ]
  • Change from baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment score with a range of 0-1 for 4 types of scores with higher scores indicating greater impairment. [ Time Frame: 12 weeks ]
  • Time to loss of efficacy, defined as discontinuation of study drug for lack of efficacy. [ Time Frame: 12 weeks ]
  • Summary of AEs and SAEs [ Time Frame: 60 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
  • Difference of average pain intensity scores from baseline to week 12 to determine the efficacy of CAM2038 once-weekly and CAM2038 once-monthly compared to placebo [ Time Frame: 12 weeks ]
  • Safety and tolerability of CAM2038 by quantifying the number of Adverse Events [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by WPAI [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by EQ5D [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by amount of rescue medication taken [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by BDI-II [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by CGI-I [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by CGI-S [ Time Frame: 12 weeks ]
  • Difference of efficacy assessments from baseline to week 12 measured by PGI-I. [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Buprenorphine (CAM2038) in Subjects With a Recent History of Moderate to Severe Chronic Low Back Pain
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lower Back Pain
  • Chronic Pain
Intervention  ICMJE
  • Drug: buprenorphine
    Other Name: CAM2038
  • Other: Placebo
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    CAM2038 placebo injections
    Intervention: Other: Placebo
  • Experimental: 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: Drug: buprenorphine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2016)
340
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2019
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Written informed consent provided prior to the conduct of any study-related procedures.
  2. Male or non-pregnant, non-lactating female subject, greater than or equal to 18 years old.
  3. Body mass index (BMI) between 18 and 38 kg/m2, inclusive.
  4. Treated with daily opioids for moderate to severe CLBP for a minimum of 3 months prior to Screening.
  5. On a stable dose of ≥40 mg/day of oral morphine or MED during the 14 days prior to Screening.
  6. Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg.
  7. 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).
  8. Male subject who is willing to use reliable contraception
  9. Willing and able to comply with all study procedures and requirements.

Exclusion Criteria:

  1. Positive for hepatitis B surface antigen, hepatitis C viral RNA, or antibodies to human immunodeficiency virus (HIV).
  2. 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:

    1. Severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, biliary tract disease, severe hepatic insufficiency, or planned surgery.
    2. Bipolar disorder
  3. 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.
  4. Female subject planning to become pregnant during the study.
  5. Surgical procedure(s) for CLBP within 6 months prior to Screening.
  6. 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.
  7. QTcF >450 ms for males and >470 ms for females, or clinically significant electrocardiogram (ECG) abnormality at Screening, at the investigator's discretion.
  8. 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.
  9. A nerve or plexus block, including epidural steroid injections or facet blocks, within 1 month prior to Screening or botulinum toxin injection in the lower back region within 3 months of Screening.
  10. History of chemotherapy or confirmed malignancy (except basal cell carcinoma) within the past 2 years.
  11. Any other acute or chronic pain condition that could interfere with the subject's ability to report their CLBP accurately and consistently and/or interfere with the study staff's ability to assess the subjects CLBP.
  12. An active or pending workman's compensation, insurance claim, or litigation related to back pain (i.e., primary claim is back pain).
  13. Clinically significant history, in the opinion of the investigator, of suicidal ideation or current evidence that the subject is actively suicidal.
  14. Clinically significant history of major depressive disorder that is poorly controlled with medication, per investigator judgment.
  15. Hypersensitivity or allergy to BPN, other opioids, or excipients of CAM2038.
  16. Hypersensitivity or allergy to acetaminophen.
  17. Use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir) within the 30 days prior to Screening,
  18. Use or planned use of natural supplements that can affect CYP3A4, such as St. John's Wort, throughout the study.
  19. Has a major bleeding disorder, such as hemophilia, or treated with high levels of anticoagulants per the investigator's discretion.
  20. Current or confirmed past diagnosis of Sphincter of Oddi dysfunction.
  21. Has a significant hepatic disease, as indicated by Screening clinical laboratory assessment results (aspartate aminotransferase, alanine aminotransferase, or lactate dehydrogenase values ≥3 × the upper limit of normal [ULN]) or has a creatinine value ≥1.5 × ULN).
  22. Is an employee of the investigator or the trial site, with direct involvement in the proposed trial or other studies under the direction of the investigator or trial site or is a family member of the investigator or of an employee of the investigator.
  23. Has any pending legal action that could prohibit participation or compliance in the study.

Criteria for Entry into the Titration Phase:

  1. After at least a 12-hour washout from the last IR morphine dose, subject must have a COWS ≥5 and an API pain score over the past 24 hours ≥5 in order to receive a test dose of Buprenex.
  2. Passed all baseline criteria, including a normal QTcF, had no change in QTcF >30 ms at 1 hour after the test dose with Buprenex, and had a COWS score <5 after the test dose with Buprenex.

Note:

  • Subjects on BPN at Screening are required to participate in the down titration and will undergo a washout period prior to the test dose and first on-study treatment. Subjects entering the study on BPN will not transition to IR Morphine, but will refrain from taking their BPN for 12 -24 hours prior to the test dose to achieve the desired washout period.
  • Subjects on BPN at Screening are still required to follow the same Day 1 procedures (e.g., confirmation of pain scores, COWS assessment and Buprenex test dose) as non-BPN subjects.

Criteria for Randomization into the Double-Blind Phase:

  1. Been on a stable dose of CAM2038 q1w for at least 2 consecutive weeks.
  2. CAM2038 titrated to a dose that provides analgesia (i.e., 7-day API score of ≤4 and at least 2 points below the value at the start of Titration Phase) and is well tolerated for 7 days before randomization.
  3. Requires no more than an average of one hydrocodone/acetaminophen 5 mg/325 mg/day during the last 7 days prior to randomization.
  4. Demonstrated study medication (CAM2038) compliance ≥80% during the previous 14 days.
  5. Demonstrated daily compliance with pain intensity scoring for ≥11 of the previous 14 days, including the last 3 days prior to randomization.

Inclusion Criteria for Open Label Extension For Subjects Continuing from The Randomized Double-Blind Phase.

Subjects must have:

  1. Completed Double Blind Phase of the study
  2. Signed Informed Consent for Safety Extension

Subjects completing the double-blind phase will be enrolled directly into the open label extension at their respective dose level of CAM2038. They will not be required to participate in a Buprenex treatment test dosing or participate in a titration phase.

For De Novo Subjects (New Subjects Recruited Directly into The Open Label Extension)

Subjects who are not participating in the Double-Blind Phase of the Study must meet all of the following inclusion criteria in order to be eligible for participation in the study:

  1. Written informed consent provided prior to the conduct of any study-related procedures.
  2. Male or non-pregnant and non-lactating female subject, greater than or equal to 18 years old.
  3. BMI between 18 and 38 kg/m2, inclusive.
  4. Treated with daily opioids for moderate to severe chronic pain disorder such as CLBP or osteoarthritis for a minimum of 3 months prior to Screening.
  5. On a stable dose of >40 mg/day of oral morphine or MED during the 14 days prior to Screening.
  6. Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg.
  7. 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).
  8. Male subject who is willing to use reliable contraception
  9. Willing and able to comply with all study procedures and requirements.

Exclusion Criteria for Subjects Continuing from The Randomized Double-Blind Phase

1. 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.

Exclusion Criteria for De Novo Subjects only:

Same exclusion criteria as for subjects participating in the Randomized Double-Blind Treatment Phase.

Criteria for Entry into the Titration Phase (for De novo subjects):

  1. After at least a 12-hour washout from the last IR morphine dose, subject should have a COWS ≥5 and an API pain score over the past 24 hours ≥5 in order to receive a test dose of Buprenex.
  2. Passed all baseline criteria, including a normal QTcF, had no change in QTcF >30 ms at 1 hour after the test dose with Buprenex, and had a COWS score <5 after the test dose with Buprenex.

Note:

  • Subjects on BPN at Screening are required to participate in the down titration and will undergo a washout period prior to the test dose and first on-study treatment. Subjects entering the study on BPN will not transition to IR Morphine, but will refrain from taking their BPN for 12 -24 hours prior to the test dose to achieve the desired washout period.
  • However, subjects on BPN at Screening are still required to follow the same Day 1 procedures (e.g., confirmation of pain scores, COWS assessment and Buprenex test dose) as non-BPN subjects.

Criteria for Enrolment into the Open Label Treatment Phase (for de Novo subjects):

  1. Been on a stable dose of CAM2038 q1w for at least 2 consecutive weeks.
  2. CAM2038 titrated to a dose that provides analgesia (i.e., 7-day API score of ≤4 and at least 2 points below the value at the start of Titration Phase) and is well tolerated for 7 days before randomization.
  3. Requires no more than an average of one hydrocodone/acetaminophen 5 mg/325 mg/day during the last 7 days prior to randomization
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02946073
Other Study ID Numbers  ICMJE HS-16-555
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Braeburn Pharmaceuticals
Study Sponsor  ICMJE Braeburn Pharmaceuticals
Collaborators  ICMJE
  • Medpace, Inc.
  • Camurus AB
Investigators  ICMJE Not Provided
PRS Account Braeburn Pharmaceuticals
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP