None listed
Conditions
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.
Interventions
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
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.
Sponsors
Douglas Pharmaceuticals Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent prior to any study specific procedures; 2. 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 26 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 Day 1/baseline); 8. Subjects must weigh at least 50kg and have a Body Mass Index (BMI) between 18 and 40 kg/m2 inclusive; 9. Subjects of childbearing potential (SOCBP) must use a highly effective form of birth control .
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.
Outcome results
None listed