A Multiple Dose Opioid Challenge Study | NCT02611752

NCT02611752

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CAM2038 q1w, 24 mg	Experimental	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	Drug: CAM2038
CAM2038 q1w, 32 mg	Experimental	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	Drug: CAM2038

Name	Type	Description	Arm Group Labels	Other Names
CAM2038	Drug	CAM2038 subcutaneous injection	CAM2038 q1w, 24 mg CAM2038 q1w, 32 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	17 days
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	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.	17 days
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	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.	17 days
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	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.

Secondary Outcomes

Measure	Description	Time Frame
Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)	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).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient had to provide written informed consent prior to the conduct of any study-related procedures.
Male or female, 18-55 years of age, inclusive.
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.
Self-reported opioid-use of a minimum of 21 days in the 30 days prior to Screening.
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.
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).
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.
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.
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:

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.
Opioid-dependent patients who were actively seeking treatment for their moderate to severe opioid use disorder.
Patients with positive UDS for BPN, barbiturates, or methadone or breath alcohol on the day of check-in to the CRU.
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.
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.
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).
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.
Current diagnosis of Acquired Immune Deficiency Syndrome.
Current diagnosis of chronic pain requiring opioids for treatment.
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.
Pregnant or lactating, or planned to become pregnant during the study.
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).
Hypersensitivity or allergy to BPN or other opioids or excipients of CAM2038.
Intolerance to venipuncture and/or difficulty with venous access, as per the judgment of the Investigator/research staff.
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).
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).
If the patient was currently on probation or had any pending legal action that could have prohibited participation or compliance in the study.
A patient who, in the opinion of the Investigator, was considered unsuitable or unlikely to comply with the study protocol for any reason.

Contacts/Locations Module

Name	Affiliation	Role
Sharon Walsh, PhD	University of Kentucky	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Vince and Associates Clinical Research		Overland Park	Kansas	66212	United States
University of Kentucky

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37584841	Derived	Bjornsson M, Acharya C, Strandgarden K, Tiberg F. Population Pharmacokinetic Analysis Supports Initiation Treatment and Bridging from Sublingual Buprenorphine to Subcutaneous Administration of a Buprenorphine Depot (CAM2038) in the Treatment of Opioid Use Disorder. Clin Pharmacokinet. 2023 Oct;62(10):1427-1443. doi: 10.1007/s40262-023-01288-6. Epub 2023 Aug 16.
28655025

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	CAM2038 q1w, 24 mg	CAM2038 once weekly 24 mg subcutaneous injection will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg intramuscular injection will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13
FG001	CAM2038 q1w, 32 mg	CAM2038 once weekly 32 mg subcutaneous injection will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg intramuscular injection will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00022 subjects FG00125 subjects
Day 1-3 Hydromorphone Challenge Injs		FG00022 subjects FG00125 subjects
Day 4-6 Hydromorphone Challenge Injs		FG00022 subjects FG00124 subjects
Day 8-10 Hydromorphone Challenge Injs		FG00022 subjects FG00124 subjects
Day11-13 Hydromorphone Challenge Injs		FG00022 subjects FG00124 subjects
COMPLETED		FG00022 subjects FG00124 subjects
NOT COMPLETED		FG0000 subjects FG0011 subjects

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0011 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	CAM2038 q1w, 24 mg	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13.
BG001	CAM2038 q1w, 32 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

Mean Drug Liking VAS Scores over Time for CAM2038 q1w 24 mg by Hydromorphone Challenge Session, Completer Population (N=22)

Posted

Least Squares Mean

Standard Error

units on a scale

17 days

ID	Title	Description
OG000	CAM2038 q1w, 24 mg - Hydromorphone 0 mg	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CAM2038 q1w, 24 mg	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg, and 18 mg intramuscular injections each being administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Constipation	Gastrointestinal disorders		Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Sonnie Kim	Braeburn	1 610 467 8717		sonnie@braeburnrx.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 17, 2015	Aug 3, 2018	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jun 13, 2016	Aug 3, 2018	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D008224	Lymphoma, Follicular
D009293	Opioid-Related Disorders

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

Intervention Browse Module

ID	Term
D002047	Buprenorphine

ID	Term
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds

Masking Info

EG0003 affected22 at risk

EG0016 affected25 at risk

OG00177.0(65.5 to 88.4)

OG00181.8(72.3 to 91.4)