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

NCT ID: NCT02946073

Last Updated: 2021-10-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1053 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2019-02-28

Brief Summary

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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

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Conditions

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Chronic Lower Back Pain Chronic Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

CAM2038 placebo injections

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Group Type EXPERIMENTAL

buprenorphine

Intervention Type DRUG

Interventions

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buprenorphine

Intervention Type DRUG

Placebo

Intervention Type OTHER

Other Intervention Names

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CAM2038

Eligibility Criteria

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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.


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)


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

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.


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.



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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medpace, Inc.

INDUSTRY

Sponsor Role collaborator

Camurus AB

INDUSTRY

Sponsor Role collaborator

Braeburn Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Parkway Medical Center

Birmingham, Alabama, United States

Site Status

Boyett Health Services Inc

Hamilton, Alabama, United States

Site Status

National Centers for Pain Management and Research

Vestavia Hills, Alabama, United States

Site Status

Elite Clinical Studies

Phoenix, Arizona, United States

Site Status

Phoenix Clinical

Phoenix, Arizona, United States

Site Status

Noesis Pharma

Phoenix, Arizona, United States

Site Status

Arizona Research Center

Phoenix, Arizona, United States

Site Status

MD Studies, Inc.

Fountain Valley, California, United States

Site Status

Neuro-Pain Medical Center

Fresno, California, United States

Site Status

Alliance Research Centers

Laguna Hills, California, United States

Site Status

Clinical Trials Research

Lincoln, California, United States

Site Status

Catalina Research Institute, LLC

Montclair, California, United States

Site Status

Allied Clinical Research, LLC

Sacramento, California, United States

Site Status

Care Practice

San Francisco, California, United States

Site Status

Syrentis Clinical Research

Santa Ana, California, United States

Site Status

Universal Pain Management Group

Valencia, California, United States

Site Status

Tampa Pain Relief Center-Brandon

Brandon, Florida, United States

Site Status

International Research Partners

Doral, Florida, United States

Site Status

Dr. Vijapura and Associates

Jacksonville, Florida, United States

Site Status

Florida Institute of Medical Research

Jacksonville, Florida, United States

Site Status

Lake Howell Health Center

Maitland, Florida, United States

Site Status

Ocean Blue Medical Research Center, Inc.

Miami Springs, Florida, United States

Site Status

Scientific Clinical Research, Inc.

North Miami, Florida, United States

Site Status

Gold Coast Research, LLC

Plantation, Florida, United States

Site Status

FMPM Research

St. Petersburg, Florida, United States

Site Status

Clinical Research of West Florida-Tampa

Tampa, Florida, United States

Site Status

Tampa Pain Relief Centers-Hillsborough

Tampa, Florida, United States

Site Status

Palm Beach Research Center

West Palm Beach, Florida, United States

Site Status

River Birch Research Alliance LLC

Blue Ridge, Georgia, United States

Site Status

Columbus Regional Research Institute

Knoxville, Georgia, United States

Site Status

Drug Studies America

Marietta, Georgia, United States

Site Status

Non-Surgical Orthopedics, P.C.

Marietta, Georgia, United States

Site Status

Injury Care Research, LLC

Boise, Idaho, United States

Site Status

Millennium Pain Center

Bloomington, Illinois, United States

Site Status

Clinical Investigation Specialists, Inc.-Gurnee

Gurnee, Illinois, United States

Site Status

Medisphere Medical Research Center

Evansville, Indiana, United States

Site Status

International Clinical Research Institute Inc.

Overland Park, Kansas, United States

Site Status

Phoenix Medical Research

Prairie Village, Kansas, United States

Site Status

Otrimed

Edgewood, Kentucky, United States

Site Status

River Cities Clinical Research Center

Shreveport, Louisiana, United States

Site Status

Boston Paincare

Waltham, Massachusetts, United States

Site Status

MedVadis Research Corporation

Watertown, Massachusetts, United States

Site Status

Amicis Trials

Festus, Missouri, United States

Site Status

Hassman Research Institute

Berlin, New Jersey, United States

Site Status

New York Clinical Trials, Inc

New York, New York, United States

Site Status

MedEx Healthcare Research, Inc-NY

New York, New York, United States

Site Status

Upstate Clinical Research Associates

Williamsville, New York, United States

Site Status

Rapha Institute for Clinical Research

Fayetteville, North Carolina, United States

Site Status

OnSite Clinical Solutions, LLC-Hickory

Hickory, North Carolina, United States

Site Status

Center for Clinical Research, LLC-Winston-Salem

Winston-Salem, North Carolina, United States

Site Status

Aventiv Research, Inc.

Columbus, Ohio, United States

Site Status

Dayton Outpatient Center (DOC) Clinical Research

Dayton, Ohio, United States

Site Status

Providence Health Partners-Center for Clinical Research

Dayton, Ohio, United States

Site Status

Medical Research Internationl

Oklahoma City, Oklahoma, United States

Site Status

SP Research, PLLC

Oklahoma City, Oklahoma, United States

Site Status

Frost Medical Group, LLC

Conshohocken, Pennsylvania, United States

Site Status

Suburban Research Associates

Media, Pennsylvania, United States

Site Status

Coastal Carolina Research Center

Charleston, South Carolina, United States

Site Status

Medical Research South, LLC

Charleston, South Carolina, United States

Site Status

New Phase Research & Development

Knoxville, Tennessee, United States

Site Status

FutureSearch Trials of Dallas, LP

Dallas, Texas, United States

Site Status

Renaissance Clinical Research and Hypertension Clinic

Dallas, Texas, United States

Site Status

Research Concepts GP, LLC-Houstion

Houston, Texas, United States

Site Status

Pioneer Research Solutions Inc.

Houston, Texas, United States

Site Status

The Pain Relief Center

Plano, Texas, United States

Site Status

The SMART Clinic/Physicians Research Options LLC

Draper, Utah, United States

Site Status

EPIC Medical Research

Murray, Utah, United States

Site Status

Aspen Clinical Research

Orem, Utah, United States

Site Status

Mid Columbia Research

Richland, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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HS-16-555

Identifier Type: -

Identifier Source: org_study_id