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Trial registered on ANZCTR


Registration number
ACTRN12618001042235p
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 Phase 2 clinical study evaluating the efficacy and safety of R-107 for the Treatment of treatment-resistant depression.
Scientific title
A Phase 2a Proof-of-Concept Study of R-107 for the Treatment of Refractory Major Depressive Disorder
Secondary ID [1] 295222 0
None
Universal Trial Number (UTN)
U1111-1214-9840
Trial acronym
BEDROC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 308373 0
Condition category
Condition code
Mental Health 307363 307363 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1: After a three week screening period to assess eligibility, approximately 200 Subjects with treatment-resistant depression will receive open-label R-107 120mg (2 x 60 mg) oral tablets once per day for 5 days. Enrolment to Part 1 of the study will continue until 150 responders enter Part 2 of the study. On Day 8, subjects will be assessed for a response using the MADRS score. All MADRS assessments will be conducted by trained raters and the scores will be calculated electronically using an eCOA platform.
Part 2: 150 subjects responding to the open-label Part 1 portion will be randomised on Day 8 to one of 5 treatment groups of 30 subjects each (placebo, R-107 30mg, R-107 60mg, R-107 120mg and R-107 180mg). There is a 3 day wash out between Days 5 and 8. Study drug will then be taken orally twice per week for 12 consecutive weeks.
Medication will be blister packed, with 3 identical tablets to be taken per dose
Placebo: 3 x placebo tabs
30mg: 1 x 30mg and 2 x placebo tabs
60mg: 1 x 60mg and 2 x placebo tabs
120mg: 2 x 60mg and 1 x placebo tabs
180mg: 3 x 60mg tabs
Subjects will take each dose (all three tablets) on days 1 and 4 of each week up to 12 weeks.
All subjects who take one dose of study drug will be followed up 4 weeks after their last dose for assessments.
Throughout the dosing phases of the study, all subjects will be required to return all empty drug bottles or unused study drug for compliance assessments.
Intervention code [1] 301558 0
Treatment: Drugs
Comparator / control treatment
Placebo-controlled. The placebo tablet is comprised of polyethylene oxide.
Control group
Placebo

Outcomes
Primary outcome [1] 306335 0
To evaluate the efficacy of extended release (ER) R-107 tablets (30mg, 60mg, 120mg, 180mg) as measured by the change in Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline (Day 1) to Day 92 in subjects with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Treatment-Resistant Depression (TRD) who have responded to 1 weeks’ treatment with R-107 120mg tablets.
Timepoint [1] 306335 0
The MADRS will be assessed at Days 1, 5, 8, 15, 22, 29, 36, 64 and Day 92 (primary endpoint).
Secondary outcome [1] 348223 0
To assess the effect of R-107 tablets compared to placebo on the severity of illness using the Clinician Global Impression – Severity (CGI-S).
Timepoint [1] 348223 0
Days 1, 8, 36, 64 and 92. Also assess at 4 week follow up visit.
Secondary outcome [2] 348307 0
To evaluate the pharmacokinetics (PK) of R-107 tablets in subjects with TRD where Tmax, AUC and T1/2 will be assessed.
Timepoint [2] 348307 0
Days 8, 64 and 92
Secondary outcome [3] 348436 0
To assess the effect of R-107 tablets compared to placebo on the severity of illness using the Patient Global Impression – Severity (PGI-S).
Timepoint [3] 348436 0
Days 1, 8, 36, 64 and 92. Also assess at 4 week follow up visit.

Eligibility
Key inclusion criteria
1. Provision of written informed consent prior to any study specific procedures;
2. Female or male subjects aged 18-80 years inclusive at the time of enrolment (screening visit);
3. Diagnosed with MDD as per Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and Mini-International Neuropsychiatric Interview (MINI) 7.0 without psychotic features for at least three months prior to screening (comorbid anxiety disorders are also acceptable);
4. Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to 20 at screening and baseline;
5. Treatment resistance in major depression (TRD) as per Maudsley Staging Method (MSM) and defined as “failure to attain significant level of improvement (equated with clinical remission) from an accurately defined depressive episode following treatment with an antidepressant medication given at an adequate (minimum effective) dose for a minimum of six weeks”;
6. Montreal Cognitive Assessment (MoCA) score greater than or equal to 23 assessing cognitive function;
7. Psychotropic medication and/or psychotherapy is stable (i.e. no change of drugs or drug dose or visit schedule within 4 weeks prior to study entry);
8. Subjects must weigh at least 50kg and have a Body Mass Index (BMI) between 18 and 40 kg/m2 inclusive;
9. Women of childbearing potential (WOCBP) must use a highly effective form of birth control .
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 subject at risk because of participation in the study, or may influence the results of the study, or the subject’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 subject at risk or negatively affect the outcome of the study;
4. Subjects are excluded if they have any of the following:
• A history of known immunodeficiency disorder including a positive test for human immunodeficiency virus, HIV-1 or HIV-2;
• Positive hepatitis B surface antigen, or positive hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol.
5. Hepatic Insufficiency: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level greater than or equal to 2 times the upper limit of normal (ULN) confirmed by repeated testing during screening period;
6. 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);
7. Significant current risk of suicide.

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)
Each medication kit will be individually numbered. Central randomisation system (IRT) will be utilised by phone/computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence will be generated by an independent statistician using statistical computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary analysis of efficacy will be performed on the change in MADRS from baseline to Day 92 and will be assessed with Mixed Model Repeated Measures (MMRM) method, with treatment, time and the interaction of treatment with time as fixed effects, subject as random effect and baseline MADRS as a covariate. The least square mean differences between each active treatment with placebo will be presented along with a 95% confidence interval.

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] 11155 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 11156 0
Gold Coast University Hospital - Southport
Recruitment hospital [3] 11157 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [4] 11158 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 11159 0
Peninsula Private Hospital - Frankston - Frankston
Recruitment hospital [6] 11160 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [7] 11161 0
Epworth Rehabilitation Camberwell - Camberwell
Recruitment hospital [8] 12386 0
Black Dog Institute - Randwick
Recruitment postcode(s) [1] 22979 0
2031 - Randwick
Recruitment postcode(s) [2] 22980 0
2050 - Camperdown
Recruitment postcode(s) [3] 22981 0
4215 - Southport
Recruitment postcode(s) [4] 22982 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 22983 0
5000 - Adelaide
Recruitment postcode(s) [6] 22984 0
3199 - Frankston
Recruitment postcode(s) [7] 22985 0
3050 - Parkville
Recruitment postcode(s) [8] 22986 0
3124 - Camberwell
Recruitment outside Australia
Country [1] 10565 0
New Zealand
State/province [1] 10565 0
Auckland, Canterbury, Otago
Country [2] 10566 0
Singapore
State/province [2] 10566 0

Funding & Sponsors
Funding source category [1] 299812 0
Commercial sector/Industry
Name [1] 299812 0
Douglas Pharmaceuticals Ltd.
Address [1] 299812 0
2 Te Pai Place
Lincoln
Auckland 0610
New Zealand
Country [1] 299812 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Douglas Pharmaceuticals Ltd.
Address
2 Te Pai Place
Lincoln
Auckland 0610
New Zealand
Country
New Zealand
Secondary sponsor category [1] 299161 0
None
Name [1] 299161 0
Address [1] 299161 0
Country [1] 299161 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 300691 0
Ethics committee address [1] 300691 0
Ethics committee country [1] 300691 0
Date submitted for ethics approval [1] 300691 0
02/07/2018
Approval date [1] 300691 0
Ethics approval number [1] 300691 0

Summary
Brief summary
Despite the many treatment options available for clinically depressed patients, there is a need for more effective treatments, particularly for TRD and specifically for therapeutic options that lead to more rapid symptom resolution. This is a multi-centre, Phase 2a study, which incorporates a 1-week enrichment open-label phase followed by randomised, double-blind, placebo-controlled phase, to investigate R-107 (30mg, 60mg, 120mg or 180mg) versus placebo in TRD subjects who respond to the 1-week enrichment open-label phase.
Each subject will participate in up to 4 phases:
• Phase 1: A screening phase of up to 3 weeks (Day -21 to -1);
• Phase 2: An enrichment phase: open-label treatment phase for 1 week (to identify responders for the enrichment population in the subsequent double-blind treatment phase);
• Phase 3: A double-blind treatment phase for 12 weeks (Day 8-92);
• Phase 4: 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 84494 0
Mr Blair Dickman
Address 84494 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84494 0
New Zealand
Phone 84494 0
+6498350660
Fax 84494 0
Email 84494 0
blaird@douglas.co.nz
Contact person for public queries
Name 84495 0
Mr Blair Dickman
Address 84495 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84495 0
New Zealand
Phone 84495 0
+6498350660
Fax 84495 0
Email 84495 0
blaird@douglas.co.nz
Contact person for scientific queries
Name 84496 0
Mr Blair Dickman
Address 84496 0
Douglas Pharmaceuticals Ltd.
2 Te Pai Place
Lincoln
Auckland 0610
Country 84496 0
New Zealand
Phone 84496 0
+6498350660
Fax 84496 0
Email 84496 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 regarding document transparency and sharing.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable