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Trial registered on ANZCTR


Registration number
ACTRN12618001759280
Ethics application status
Approved
Date submitted
12/10/2018
Date registered
25/10/2018
Date last updated
25/10/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Depot Evaluation Buprenorphine Utilization Trial (DEBUT)
Scientific title
A Randomised, Open-Label, Multi-center Trial Comparing a Once-Weekly and Once-Monthly Long-Acting Subcutaneous Injectable Depot of Buprenorphine (CAM2038) to Buprenorphine Standard of Care in Adult Outpatients with Opioid Dependence
Secondary ID [1] 296138 0
HS-17-585
Universal Trial Number (UTN)
HS-17-585
Trial acronym
The Depot Evaluation Buprenorphine Utilization Trial (DEBUT)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid dependent 309726 0
Condition category
Condition code
Mental Health 308535 308535 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CAM2038 uses a unique, low viscosity, lipidbased FluidCrystal® injection depot
technology containing dissolved buprenorphine (BPN) and is subcutaneously (SC) administered (alternated between the different injection areas i.e., the buttock, thigh, abdomen, or upper arm) by healthcare professionals at weekly (CAM2038 once weekly [q1w]) or monthly (CAM2038 once monthly [q4w]) intervals. Patients receiving CAM2038 can be switched between the weekly and monthly products at any time during the entire trial at the discretion of the treating Investigator.

The treatment duration is 24 weeks.
Intervention code [1] 312468 0
Lifestyle
Intervention code [2] 312665 0
Treatment: Drugs
Comparator / control treatment
BPN standard of care (for example, sublingual (SL) BPN or BPN/naloxone(NX)) for medication assisted treatment (MAT) of opioid dependence at licensed doses
Control group
Active

Outcomes
Primary outcome [1] 307510 0
Objective: To compare patient satisfaction with CAM2038 to buprenorphine (BPN) standard of care in adult outpatients with opioid dependence.
Endpoint: Treatment Satisfaction Questionnaire for Medication (TSQM) global satisfaction score.
Timepoint [1] 307510 0
TSQM performed at Baseline (Day 1), Week 4, Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [1] 352117 0
Objective: To assess patient satisfaction with treatment.
Endpoint:
TSQM effectiveness score
TSQM side effects score
TSQM convenience score
Patient satisfaction visual analogue scale (VAS)
Timepoint [1] 352117 0
TSQM and Patient satisfaction VAS performed at Baseline (Day 1), Week 4, Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [2] 352118 0
Objective: To assess treatment effects on illicit, non-prescribed and unsanctioned prescribed use of opioids.
Endpoint: Illicit opioid drug use measured by urine drug screen (UDS) and self-reports of illicit opioid drug use by timeline follow-back method (TLFB).
Timepoint [2] 352118 0
UDS and TLFB performed at Screening, Baseline (Day 1), every 4 weeks for 24 weeks post Baseline (Day 1), and Premature Discontinuation.
Secondary outcome [3] 352133 0
Objective: To assess treatment effects on illicit drug use other than opioids.
Endpoint: Illicit drug use measured by UDS and self-reports of drug use by Australian Treatment Outcomes Profile (ATOP).
Timepoint [3] 352133 0
UDS and ATOP performed at Screening, Baseline (Day 1), every 4 weeks for 24 weeks post Baseline (Day 1), and Premature Discontinuation.
Secondary outcome [4] 352134 0
Objective: To assess treatment effects on retention in treatment.
Endpoint: Retention in treatment.
Timepoint [4] 352134 0
Retention in treatment is calculated as days in treatment since randomization until the last day of medication during the 24 weeks of treatment (plus the respective duration of CAM2038 q1w, CAM2038 q4w or BPN standard of care).
Secondary outcome [5] 352135 0
Objective: To assess treatment effects on adherence to medication.
Endpoint: Trial drug adherence measured by dispensing records (for CAM2038) and self-reports of drug accountability (for BPN standard of care).
Timepoint [5] 352135 0
Monthly for 24 weeks from Baseline (Day 1).
Secondary outcome [6] 352136 0
Objective: To assess treatment effects on quality of life and patient functioning.
Endpoint:
Substance Use Recover Evaluator (SURE)
EuroQol five dimensions health questionnaire (EQ-5D)
Opioid Substitution Treatment Quality of Life Scale (OSTQOL)
Patient Global Impression of Change (PGIC).

This is a composite secondary outcome.
Timepoint [6] 352136 0
SURE, EQ-5D and OSTQOL performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
PGIC performed at Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [7] 352137 0
Objective: To assess the effect on treatment related behaviours and perception of treatment.
Endpoint: Treatment Burden Questionnaire (TBQ)
Opioid Related Behaviours In Treatment (ORBIT) scale.

This is a composite secondary outcome.
Timepoint [7] 352137 0
TBQ and ORBIT performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [8] 352138 0
Objective: To assess treatment effects of measures of general physical, mental and psychosocial functioning.
Endpoint: Short Form 36 (SF-36)
Depression, Anxiety and Stress Scale 21 (DASS-21).

This is a composite secondary outcome
Timepoint [8] 352138 0
SF-36 and DASS-21 performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [9] 352139 0
Objective: To assess treatment effects on health economic outcomes (HEOs) including treatment utilization.
Endpoint:
Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH)
Estimates of health care resource utilization (HRU) through modified Alcohol & Drug adapted Adult Service Use Schedule (AD-SUS) questionnaire
Estimates of social service utilisation (AD-SUS questionnaire)
Estimation of quality-adjusted life years (QALYs).

This is a composite secondary outcome
Timepoint [9] 352139 0
WPAI:GH, AD-SUS and QALYs performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [10] 352140 0
Objective: To assess treatment effects on criminal activity.
Endpoint: Criminal offences and incarcerations during the trial (AD-SUS questionnaire).
Timepoint [10] 352140 0
AD-SUS performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [11] 352141 0
Objective: To assess treatment effects on diversion and misuse of the trial medications.
Endpoint: Self-reported diversion and misuse of the trial medications using ORBIT (for BPN standard of care)
Self-reported overdoses.
Timepoint [11] 352141 0
ORBIT performed at Baseline (Day 1), Week 12, Week 24, and Premature Discontinuation.
Self-reported overdoses performed every 4 weeks for 24 weeks post Baseline (Day 1), and Premature Discontinuation.
Secondary outcome [12] 352142 0
Objective: To assess treatment effects on opioid withdrawal symptoms.
Endpoint: Clinical Opiate Withdrawal Scale (COWS).
Timepoint [12] 352142 0
COWS performed at Baseline (Day 1), Week 4, Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [13] 352143 0
Objective: To assess treatment effects on opioid cravings.
Endpoint: Craving visual analogue scale (Craving VAS).
Timepoint [13] 352143 0
Craving VAS performed at Baseline (Day 1), Week 4, Week 12, Week 24, and Premature Discontinuation.
Secondary outcome [14] 352144 0
Objective: To assess the safety and tolerability of CAM2038.
Endpoint: AEs.
At every clinic visit, patients will be asked a standard question to elicit any medically related changes in their well-being. They will also be asked if they have been hospitalised, had any accidents, used any new medications, or changed concomitant medication regimens (both prescription and over-the-counter medications).
Timepoint [14] 352144 0
AEs collected at Screening, Baseline (Day 1), every month for 24 weeks post Baseline (Day 1), every other visit where trial treatment is administered, Premature Discontinuation, and Week 26 (follow up).

Eligibility
Key inclusion criteria
Adult male or female patient (18 years or older)
Meet the criteria for opioid dependence as defined by either the criteria for moderate to severe opioid use disorder in the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition (DSM-5) OR opioid dependence in the International Statistical Classification of Diseases and Related Health Problems – 10th Edition (ICD-10) according to local practice.
Appropriate candidate for MAT with a partial opioid agonist as determined by the Investigator and is willing to continue in BPN treatment for the duration of the trial.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Requires chronic use of agents that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4) such as some azole antifungals (e.g. ketoconazole), macrolide antibiotics (e.g. clarithromycin), or protease inhibitors (e.g. ritonavir, indinavir, and saquinavir).

Hypersensitivity or intolerance to BPN or NX or any related drug.

Having a contraindicated serious medical condition including unstable and severe pain in the opinion of the investigator.

Clinically significant laboratory and ECG abnormalities.

Recent history of significant suicidal ideation or active suicidal behavior, in the opinion of the Investigator.

Participants with serious untreated psychiatric comorbidity at the discretion of the Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomization by Phone / web
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation of randomization numbers will be performed centrally using an
interactive voice/web response allocation system (IV/WRS) (dynamic (adaptive) random allocation methods).
Stratification by new to treatment will be applied (i.e. by patients who have not received MAT within 30 days before Screening).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Primary Efficacy Analysis
The Week 24 assessment in TSQM global satisfaction score, is the primary variable. and will be analysed over time by a longitudinal data analysis method using Mixed Model Repeated Measures (MMRM) methods.

Secondary Efficacy Analyses
- For continuous endpoints, the same methodology as for the primary endpoint will be used.

- For variables based on UDS, the percent weeks will be analysed in an analysis of variance with treatment as factor. The cumulative distribution function of these variables will be compared between treatments with a Wilcoxon test.

- Retention in treatment will be compared between treatments with a log-rank test.

- Health-economic endpoints will be summarised using descriptive statistics.

Safety Analyses
AEs will be summarised using descriptive statistics.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 12014 0
The Langton Centre - Surry Hills
Recruitment hospital [2] 12015 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 12016 0
Drug and Alcohol Clinical Services, Hunter New England Local Health District - Newcastle
Recruitment hospital [4] 12017 0
Blacktown Hospital - Blacktown
Recruitment hospital [5] 12018 0
Drug & Alcohol Services South Australia (DASSA) - Stepney
Recruitment hospital [6] 12019 0
Turning Point Drug and Alcohol Centre - Richmond
Recruitment postcode(s) [1] 24138 0
2010 - Surry Hills
Recruitment postcode(s) [2] 24139 0
2050 - Camperdown
Recruitment postcode(s) [3] 24140 0
2300 - Newcastle
Recruitment postcode(s) [4] 24141 0
2148 - Blacktown
Recruitment postcode(s) [5] 24142 0
5069 - Stepney
Recruitment postcode(s) [6] 24144 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 300724 0
Commercial sector/Industry
Name [1] 300724 0
Camurus AB
Address [1] 300724 0
Global Sponsor:
Camurus AB
Ideon Science Park
Sölvegatan 41
SE 223 70 Lund, Sweden

Contract Research Organisation – Local Sponsor:
PAREXEL International Pty Ltd.
15 Talavera Road
Suite B, Level 6
Macquarie Park, Australia NSW 2113

Country [1] 300724 0
Sweden
Primary sponsor type
Commercial sector/Industry
Name
Camurus AB
Address
Camurus AB
Ideon Science Park
Sölvegatan 41
SE 223 70 Lund, Sweden
Country
Sweden
Secondary sponsor category [1] 300295 0
None
Name [1] 300295 0
Address [1] 300295 0
Country [1] 300295 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301506 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 301506 0
Room G71, East Wing
Edmung Blacket Building
Prince of Wales Hospital
Randwick NSW 2031

Ethics committee country [1] 301506 0
Australia
Date submitted for ethics approval [1] 301506 0
16/04/2018
Approval date [1] 301506 0
10/07/2018
Ethics approval number [1] 301506 0
18/093 (HREC/18/POWH/226)

Summary
Brief summary
This is a prospective, randomised, openlabel, activecontrolled, multicenter
trial comparing treatment effects of CAM2038 (BPN depot injection) with BPN standard of care (for example, sublingual [SL] BPN or BPN/naloxone [BPN/NX]) in adult outpatients with opioid dependence.
Opioid dependent patients who are either currently receiving medication assisted treatment (MAT) with SL BPN or BPN/NX, or patients who are actively seeking BPN standard of care treatment but who have not yet begun a treatment regimen, may be eligible for the trial.
Patients will be randomised in a 1:1 ratio to either CAM2038 (involving either weekly or monthly depot injections based upon prescriber and patient choice) or BPN standard of care MAT. Stratification by new to treatment will be applied.
The trial will consist of a Screening Period of up to 4 weeks duration, a Treatment Period of 24 weeks duration, and a Followup Period of 2 weeks duration.
Outcomes relevant to study include the treatments’ perspective impact on patient’s satisfaction of treatment and other patient reported outcomes (PROs), as well as understanding the potential health economic impact and resource utilization with CAM2038 treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87230 0
Prof Nicholas Lintzeris
Address 87230 0
The Langton Centre
591 South Dowling Street
Surry Hills NSW 2010
Australia
Country 87230 0
Australia
Phone 87230 0
+61 419261675
Fax 87230 0
Email 87230 0
Nicholas.Lintzeris@health.nsw.gov.au
Contact person for public queries
Name 87231 0
Ms Lauren Rogers
Address 87231 0
PAREXEXL International
Suite B, Level 6
15 Talavera Road
North Ryde, NSW 2113
Australia
Country 87231 0
Australia
Phone 87231 0
+61 2 8870 3175
Fax 87231 0
Email 87231 0
Lauren.Rogers@PAREXEL.com
Contact person for scientific queries
Name 87232 0
Ms Lauren Rogers
Address 87232 0
PAREXEL International
Suite B, Level 6
15 Talavera Road
North Ryde, NSW 2113
Australia
Country 87232 0
Australia
Phone 87232 0
+61 2 8870 3175
Fax 87232 0
Email 87232 0
Lauren.Rogers@PAREXEL.com

No data has been provided for results reporting
Summary results
Not applicable