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A Multiple Dose Opioid Challenge Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02611752
Recruitment Status : Completed
First Posted : November 23, 2015
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
Braeburn Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 18, 2015
First Posted Date  ICMJE November 23, 2015
Results First Submitted Date  ICMJE August 3, 2018
Results First Posted Date  ICMJE November 14, 2019
Last Update Posted Date November 14, 2019
Study Start Date  ICMJE October 2015
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2019)
  • Treatment Phase Drug Liking Visual Analog Scale (VAS) Emax Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg [ Time Frame: 17 days ]
    Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
  • Treatment Phase Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 32 mg [ Time Frame: 17 days ]
    Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population), where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
  • Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) for Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 24 mg [ Time Frame: 17 days ]
    Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
  • Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 32 mg [ Time Frame: 17 days ]
    Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 32 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2015)
To evaluate the degree of opioid blocking effects of CAM2038 following administration of intramuscular hydromorphone compared to administration of placebo on subjective opioid effects via Visual Analog Scale [ Time Frame: 14 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2019)
  • Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [ Time Frame: 15 days ]
    Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel high" where values can range from 0 (Not at all High) to 100 (Extremely High).
  • Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [ Time Frame: 15 days ]
    Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseling and four challenge sequences with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel good drug effects" where values can range from 0 (Not at all ) to 100 (Extremely).
  • Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w Group (Completer Population) [ Time Frame: 15 days ]
    Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).
  • Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w Group (Completer Population) [ Time Frame: 15 days ]
    Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).
  • Analysis Results for Unipolar Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [ Time Frame: 15 days ]
    Analysis Results for Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I desire opiods" where values can range from 0 (Definitely not) to 100 (Definitely so).
  • Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [ Time Frame: 15 days ]
    Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, my mental state is" where values can range from 0 (Very Drowsy) to 100 (Very alert), with 50 being neutral (Neither drowsy nor alert).
  • Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [ Time Frame: 15 days ]
    Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I fell any drug effects" where values can range from 0 (Not at all) to 100 (Extremely).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2015)
  • Plasma buprenorphine concentration levels at daily time points will be compared to the subjective effects of hydromorphone via Visual Analog Scale [ Time Frame: 14 days ]
  • Safety and tolerability will be assessed through TEAEs; hematologic and laboratory parameters; and vital signs measurements. [ Time Frame: 14 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multiple Dose Opioid Challenge Study
Official Title  ICMJE A Multiple Dose Opioid Challenge Study to Assess Blockade of Subjective Opioid Effects of CAM2038 q1w (Buprenorphine FluidCrystal® Subcutaneous Injection Depots) In Adults With Opioid Use Disorder
Brief Summary Multi-site, randomized, double-blind, repeat-dose Phase 2 study to evaluate the degree and duration of action of multiple doses of CAM2038 in blocking the effects of hydromorphone in patients with moderate or severe opioid use disorder.
Detailed Description

This is a multi-site, randomized, double-blind, repeat-dose Phase 2 study to evaluate the degree and duration of action of multiple doses of CAM2038 q1w in blocking the effects of a mu opioid agonist (hydromorphone) in patients with moderate or severe opioid use disorder. The study will involve 4 phases: Screening, Qualification, Treatment, and Follow-up.

The study will enroll a sufficient number of subjects to ensure that at least 48 subjects complete the study (24 subjects per group with at least 16 females in total). Replacement subjects may be added at the discretion of the sponsor with the agreement of the investigator.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Moderate or Severe Opioid Use Disorder
Intervention  ICMJE Drug: CAM2038
CAM2038 subcutaneous injection
Study Arms  ICMJE
  • Experimental: CAM2038 q1w, 24 mg
    CAM2038 q1w 24 mg will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13
    Intervention: Drug: CAM2038
  • Experimental: CAM2038 q1w, 32 mg
    CAM2038 q1w 32 mg will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13
    Intervention: Drug: CAM2038
Publications * Walsh SL, Comer SD, Lofwall MR, Vince B, Levy-Cooperman N, Kelsh D, Coe MA, Jones JD, Nuzzo PA, Tiberg F, Sheldon B, Kim S. Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):894-902. doi: 10.1001/jamapsychiatry.2017.1874.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: May 9, 2016)
47
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2015)
48
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient had to provide written informed consent prior to the conduct of any study-related procedures.
  2. Male or female, 18-55 years of age, inclusive.
  3. Patients with a diagnosis of moderate or severe opioid use disorder (DSM-V) who were physically dependent on intravenous (IV) or insufflated opioids, and who were willing to undergo short-term BPN treatment.
  4. Self-reported opioid-use of a minimum of 21 days in the 30 days prior to Screening.
  5. Positive UDS for opioids at Screening or at check-in. If UDS was not positive, patients had to present with physical signs of withdrawal, as determined by the Investigator. The Investigator may have administered a naloxone challenge, in order to confirm opioid dependence at the Investigator's discretion.
  6. Female patients of childbearing potential had to be willing to use a reliable method of contraception during the entire study (Screening Visit to Follow-up Phone Call).
  7. Female patients of non-childbearing potential were surgically sterile (i.e., had undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels.
  8. Male patients with female partners of childbearing potential had to agree to use a reliable method of contraception from Screening Visit through at least 3 months after the last dose of study drug. Male patients also must have agreed not to donate sperm during the study through at least 3 months after the last dose of study drug.
  9. Were willing and able to comply with the study requirements (including blood sampling), complete study assessments, visit the clinic, and remain confined in the CRU for up to 25 consecutive days.

Exclusion Criteria:

  1. History or presence of any clinically significant psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major disease or illness at Screening, which in the opinion of the Investigator would have jeopardized the safety of the patient or the validity of the study results.
  2. Opioid-dependent patients who were actively seeking treatment for their moderate to severe opioid use disorder.
  3. Patients with positive UDS for BPN, barbiturates, or methadone or breath alcohol on the day of check-in to the CRU.
  4. Aspartate aminotransferase (AST) levels >3 X the upper limit of normal, alanine aminotransferase (ALT) levels >3 X the upper limit of normal, total bilirubin >1.5 X the upper limit of normal, or creatinine >1.5 X the upper limit of normal on the Screening laboratory assessments and at inpatient check-in, or other clinically significant laboratory abnormalities, which in the opinion of the Investigator may have prevented the patient from safely participating in study.
  5. Any clinically significant abnormality on the basis of medical history, vital signs, physical examination, 12-lead electrocardiogram ([ECG], QTcF ≥450 msec for males or ≥470 msec for females), and laboratory evaluation (including hematology, clinical chemistry, urinalysis, and serology [optional]) at Screening, in the opinion of the Investigator.
  6. Significant symptoms, medical conditions, or other circumstances which, in the opinion of the Investigator, would have precluded compliance with the protocol, adequate cooperation in the study or obtaining informed consent, or may have prevented the patient from safely participating in study (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for CAM2038).
  7. Patients were carefully screened to exclude individuals presenting with a clinically significant history of seizure disorders, history of asthma or other respiratory disorders, head injury, hypertension, or personal history of cardiovascular disease or clinically significant ECG abnormalities.
  8. Current diagnosis of Acquired Immune Deficiency Syndrome.
  9. Current diagnosis of chronic pain requiring opioids for treatment.
  10. Patients who met the criteria for a diagnosis of moderate or severe substance use disorder according to DSM-V criteria for any other substances other than opioids, caffeine, or tobacco.
  11. Pregnant or lactating, or planned to become pregnant during the study.
  12. Clinically significant history of or current evidence of suicidal ideation or active suicidal behavior as based on the Columbia-Suicide Severity Rating Scale (C-SSRS; grade 4 or 5).
  13. Hypersensitivity or allergy to BPN or other opioids or excipients of CAM2038.
  14. Intolerance to venipuncture and/or difficulty with venous access, as per the judgment of the Investigator/research staff.
  15. Patient was using an investigational drug or monoamine oxidase inhibitor or had used such within the last 30 days (or 5 times the half-life of the drug, if known and longer) prior to first drug administration in the Qualification Phase (i.e., IR morphine sulfate).
  16. Required current use of agents that were 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).
  17. If the patient was currently on probation or had any pending legal action that could have prohibited participation or compliance in the study.
  18. A patient who, in the opinion of the Investigator, was considered unsuitable or unlikely to comply with the study protocol for any reason.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (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 NCT02611752
Other Study ID Numbers  ICMJE HS-13-478
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Braeburn Pharmaceuticals
Study Sponsor  ICMJE Braeburn Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sharon Walsh, PhD University of Kentucky
PRS Account Braeburn Pharmaceuticals
Verification Date August 2018

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