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Trial registered on ANZCTR


Registration number
ACTRN12618001048279p
Ethics application status
Not yet submitted
Date submitted
15/06/2018
Date registered
22/06/2018
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Multicentre, Open-Label, Phase 2 Safety Extension Study to Evaluate the Safety and Tolerability of R-107 in subjects with Refractory Major Depressive Disorder.
Scientific title
A Multicentre, Open-Label, Phase 2 Safety Extension Study to Evaluate the Safety and Tolerability of R-107 in subjects with Refractory Major Depressive Disorder.
Secondary ID [1] 295223 0
None
Universal Trial Number (UTN)
U1111-1214-9908
Trial acronym
BEDROC-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 308374 0
Condition category
Condition code
Mental Health 307364 307364 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Extended Release R-107 oral tablets (60 mg). Subjects will be dosed initially with 120mg (2 x 60mg tablets) twice a week. Subjects will be assessed for response at each scheduled clinic visit and may increase the dose to 180mg (3 x 60mg tablets) twice a week or decrease the dose to 60mg (1 x 60mg tablet) twice a week. All participants will be provided with guidance on how and when to take their study drug dose. All participants will also be given a Reminder Card informing them to take the tablets twice a week on days 1 and 4.
Subjects will continue treatment for 24 weeks or until they meet withdrawal criteria. Subjects will be required to returned all study drug bottles for compliance assessments.
A subject will be withdrawn from the study for any of the following reasons:
• Lost to follow-up;
• Withdrawal of consent;
• Violation of protocol procedures (determined on a case by case basis);
• The subject becomes pregnant.

Subjects showing clinically significant worsening of symptoms (as measured through change in MADRS, CADSS, C-SSRS, BPIC-SS score) will be immediately withdrawn from the study if:
• MADRS score greater or equal to 22
OR
• The Principal Investigator sees fit that a subject is withdrawn because of significant tolerability and/or safety issues.
Intervention code [1] 301559 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306337 0
To evaluate the safety and tolerability of extended release (ER) R-107 tablets in subjects with Refractory Major Depressive Disorder who have completed the R107-C205 (BEDROC) study. Safety and tolerability will be assessed by reviewing adverse events, vital signs and ECGs (assessed centrally by a cardiologist).
Timepoint [1] 306337 0
Primary outcome will be assessed upon completion of the 24 week treatment period.
Secondary outcome [1] 348226 0
Assessment of MADRS score during the open-label study and for 4 weeks post-treatment.
Timepoint [1] 348226 0
MADRS score will be assessed 4-weekly for up to 24-weeks post treatment commencement.

Eligibility
Key inclusion criteria
Subjects must meet all of the following criteria:
1. Provision of written informed consent prior to any study specific procedures
2. Female or male subjects aged 18-81 years inclusive at the time of enrolment (Screening visit).
3. Enrolled into the double-blind treatment phase of the R107-C205 (BEDROC) study.
4. Met relapse criteria at or before Day 92 of the R107-C205 study; or have completed the R107-C205 study.
5. Treatment resistance in major depression defined as lack of clinically meaningful improvement despite the use of adequate doses of at least two antidepressant agents, derived from the group(s) of commonly used first line treatment, prescribed for adequate duration with adequate affirmation of treatment adherence.
Minimum age
18 Years
Maximum age
81 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects must NOT meet any of the following exclusion criteria to be enrolled:
1. Any significant disease or disorder (e.g., cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study.
2. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening and at baseline, which in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject’s ability to complete entire duration of the study.
3. Any ECG abnormality obtained during the screening period that in Investigator’s judgement may put the patient at risk or negatively affect the outcome of the study.
4. Pregnant, breastfeeding, or lactating women (Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1).
5. Significant current risk of suicide

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All safety and tolerability data will be analysed using the Safety Set. The Safety Set will include all subjects who received at least one administration of the study medication. The Open-Label Safety Set will comprise all subjects who received at least one administration of the study medication during the open-label phase.

Recruitment
Recruitment status
Not yet 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,QLD,SA,VIC
Recruitment hospital [1] 11162 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 11164 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 11165 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 11166 0
Epworth Rehabilitation Camberwell - Camberwell
Recruitment hospital [5] 11167 0
Peninsula Private Hospital - Frankston - Frankston
Recruitment hospital [6] 11168 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [7] 11169 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 12387 0
Black Dog Institute - Randwick
Recruitment postcode(s) [1] 22987 0
4215 - Southport
Recruitment postcode(s) [2] 22989 0
2050 - Camperdown
Recruitment postcode(s) [3] 22990 0
3050 - Parkville
Recruitment postcode(s) [4] 22991 0
3124 - Camberwell
Recruitment postcode(s) [5] 22992 0
3199 - Frankston
Recruitment postcode(s) [6] 22993 0
5112 - Elizabeth Vale
Recruitment postcode(s) [7] 22994 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 10567 0
New Zealand
State/province [1] 10567 0
Auckland, Canterbury, Otago
Country [2] 10568 0
Singapore
State/province [2] 10568 0

Funding & Sponsors
Funding source category [1] 299813 0
Commercial sector/Industry
Name [1] 299813 0
Douglas Pharmaceuticals Ltd.
Address [1] 299813 0
2 Te Pai Place
Lincoln
Auckland 0610
Country [1] 299813 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Douglas Pharmaceuticals Ltd.
Address
2 Te Pai Place
Lincoln
Auckland 0610
Country
New Zealand
Secondary sponsor category [1] 299163 0
None
Name [1] 299163 0
Address [1] 299163 0
Country [1] 299163 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 300693 0
Ethics committee address [1] 300693 0
Ethics committee country [1] 300693 0
Date submitted for ethics approval [1] 300693 0
02/07/2018
Approval date [1] 300693 0
Ethics approval number [1] 300693 0

Summary
Brief summary
Multi-centre Phase 2a open-labelled extension study of R-107 in MDD treatment resistant subjects who responded to treatment in the R107-C205 (BEDROC) study.

Each subject will participate in up to 3 phases:
• A screening phase of up to 3 weeks
• An open-label treatment phase for 24 weeks
• A 4-week post-treatment (follow up) phase
Trial website
Not Applicable
Trial related presentations / publications
Not Applicable
Public notes
Not Applicable

Contacts
Principal investigator
Name 84498 0
Mr Blair Dickman
Address 84498 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84498 0
New Zealand
Phone 84498 0
+6498350660
Fax 84498 0
Email 84498 0
blaird@douglas.co.nz
Contact person for public queries
Name 84499 0
Mr Blair Dickman
Address 84499 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84499 0
New Zealand
Phone 84499 0
+6498350660
Fax 84499 0
Email 84499 0
blaird@douglas.co.nz
Contact person for scientific queries
Name 84500 0
Mr Blair Dickman
Address 84500 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84500 0
New Zealand
Phone 84500 0
+6498350660
Fax 84500 0
Email 84500 0
blaird@douglas.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
No decision has been made yet on document sharing/transparency.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable