A Study to Evaluate the Efficacy and Safety of MIN-117 in Adult Patients With Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
MIN-117C03 is a 6-week, 3-arm, randomized, double-blind, placebo controlled study to investigate the safety and efficacy of MIN-117 in male and female patients with Major Depressive Disorder, aged 18 to 65 years. Approximately 324 patients were to be randomly assigned to 1 of 3 treatment arms, including placebo, 2.5 mg MIN-117, or 5.0 mg MIN-117, in a 2:1:1 ratio.

Official Title
-----------------
A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study to Evaluate the Efficacy and Safety of 2 Fixed Doses (5.0 mg or 2.5 mg) of MIN-117 in Adult Patients With Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: MIN-117 5.0 mg
* Drug: MIN-117 2.5 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be able to read and understand the consent forms, complete study-related procedures, and communicate with the study staff. Participants must have provided written consent to participate in the study and understand that they are free to withdraw from the study at any time. Participants must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study in order to participate in the optional pharmacogenomic component of this study. Refusal to consent for this component does not exclude a participant from participation in the clinical study. Participants must be aged 18 to 65 years, inclusive, at Screening (Visit 1). Meet Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria for diagnosis of moderate or severe major depression with anxious distress and without psychotic features at Screening based on clinical assessment and on the Structured Clinical Interview for DSM-5 (SCID-5). Their major depressive episode must be deemed valid using the Massachusetts General Hospital (MGH) State versus trait; Assessability; Face validity; Ecological validity; and Rule of three Ps [pervasive, persistent, and pathological] (SAFER) criteria interview administered by remote, independent raters. Participants must be within a body mass index (BMI) of ≥ 18 to < 35 kg/m2 (BMI = weight (kg)/height(m)2] at Screening (Visit 1). Participants have a history of at least one previous episode of depression prior to the current episode. Participant must have been treated with an antidepressant administered at an adequate dose and duration in the past for the treatment of Major Depression. An adequate treatment is defined as an antidepressant treatment for at least 4 weeks at at least the minimum therapeutic dose, for any particular antidepressant. Current major depressive episode of at least 4 weeks in duration. At Screening (Visit 1) and Baseline (Visit 2), participants must have a score ≥ 40 on the patient rated Inventory of Depressive Symptoms self-report (IDS-SR30). At Screening (Visit 1) and Baseline (Visit 2), participants must have a score ≥ 18 on Hamilton Anxiety Scale (HAM-A). At Screening (Visit 1) and Baseline (Visit 2), participants must have a score ≥ 4 on the investigator-rated Clinical Global Impression of Severity Scale (CGI-S). Participants must be outpatients at the time of randomization (Baseline [Day 1]). Participants must be in good general health prior to study participation with no clinically relevant abnormalities as assessed by the investigator and determined by: medical history, physical examination, vital signs, blood chemistry, hematology, urinalysis, and electrocardiogram (ECG). If female, the participant must: be post-menopausal, or have had a hysterectomy or tubal ligation or be otherwise incapable of pregnancy, or must agree to consistent use of 2 methods of contraception for the duration of the study and until 90 days after the last dose of study medication. Female participants of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and negative serum and urine pregnancy test at Baseline (Visit 2). Exclusion Criteria: A DSM-5 diagnosis of current (active): panic disorder, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), anorexia nervosa, or bulimia nervosa. History or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, or borderline personality disorders, mood disorder with postpartum onset, somatoform disorders, fibromyalgia, or idiopathic medical conditions. At significant clinical risk for suicidal or violent behavior. History of treatment within last 6 months with electroconvulsive therapy (ECT), Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), or Transcranial Magnetic Stimulation (TMS). Potential participant who in the opinion of the investigator should not discontinue, or participate in washout of a prohibited concomitant medication. Potential participant who demonstrates a greater than 25% decrease in depressive symptoms as reflected by the IDS-SR30 total score from Screening visit to Baseline visit. Active cardiovascular disease (including but not limited to: atrial fibrillation or flutter, second and third-degree atrioventricular heart block, resting supraventricular tachycardia > 100 beats per minute, unstable ischemic heart disease, valvular abnormality, sick sinus syndrome or other condition requiring pacemaker) or diastolic blood pressure > 105 mmHg. Any serious, untreated, or unstable illnesses, such as: liver or renal insufficiency. Any significant pulmonary, endocrine, or metabolic disturbances. Documented disease of the central nervous system that could interfere with the study assessments (including by not limited to: stroke, tumor, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, seizure disorder requiring current anti-convulsants, traumatic brain injury or trauma, and neurosyphilis. Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for at least 3 months prior to Screening (a normal thyroid-stimulating hormone [TSH] is required prior to randomization at Baseline). Any medical condition that can potentially alter oral enteral absorption (e.g., gastrectomy), metabolism (e.g., liver failure), or excretion (e.g., renal failure) of the study drug. History of alcohol or substance use disorders (except nicotine and caffeine) meeting DSM-5 criteria within 1-year prior to Screening visit. Positive alcohol and urine drug screen for opiates, cocaine, barbiturates, tetrahydrocannabinol, methadone, tricyclic antidepressants, benzodiazepines, and amphetamine/methamphetamine at Screening or Baseline. Patients with positive testing at Screening due to prescribed benzodiazepines, tricyclic antidepressants, barbiturates or opiates are accepted but must test negative at Baseline. Male participants who have pregnant partners. Received an experimental drug or used an experimental medical device within 60 days before the planned start of treatment (Day 1) or have participated in 2 or more clinical trials in the previous 2 years. QT interval corrected with Fridericia's formula (QTcF) at Screening or Baseline greater than 450 msec for males and 470 msec for females. Positive hepatitis B surface antigen, or hepatitis C antibody or Human Immunodeficiency Virus (HIV) 1 and 2 antibodies at Screening. Employees of the investigator or study center, when the employee has direct involvement in the proposed study or other studies under the direction of that investigator or study center; also family members of the employee or the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5.0 mg MIN-117<br>MIN-117 5.0 mg (consisting of two 2.5 mg capsules) orally daily for 6 weeks | Drug: MIN-117 5.0 mg<br>* 5.0 mg MIN-117 administered as two MIN-117 2.5 mg capsules as a single dose once daily<br>|
| Experimental: 2.5 mg MIN-117<br>MIN-117 2.5 mg (consisting of one 2.5 mg capsule and one placebo capsule) orally daily for 6 weeks | Drug: MIN-117 2.5 mg<br>* 2.5 mg MIN-117 administered as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose once daily<br>|
| Placebo Comparator: Placebo<br>Placebo (consisting of two placebo capsules) orally daily for 6 weeks | Drug: Placebo<br>* Placebo administered as two Placebo capsules as a single dose once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The Montgomery-Asberg Depression Rating Scale (MADRS) is a validated, physician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The test consists of 10 items, each scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe conditions. MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. The test exhibits high inter-rater reliability and its capacity to differentiate between responders and nonresponders to antidepressant treatment has been shown to be comparable to the Hamilton Rating Scale for Depression. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Anxiety Scale (HAM-A) | Hamilton Anxiety Scale (HAM-A) measures the severity of a participant's anxiety, based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints and behavior at the interview. The subject is asked to rate the gravity of each item using a 5-level scale - from 0 to 4, where 0 being not present and 4 being severe - and afterwards, the results are collated and tabulated to determine the severity of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-25 mild to moderate severity, 25-30 moderate to severe, and >30 indicates very severe. To implement the HAM-A, the acting clinician proceeds through the 14 items, evaluating each criterion independently in form of the five-point scale described above. | Change from Baseline to the end of Week 6 | 
| Change in Clinical Global Impression of Severity Scale (CGI-S) | The Clinical Global Impression of Severity (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? which is rated on the following scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. The CGI-S will provide an overall clinician-determined summary measure that takes into account all available information including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. | Change from Baseline to Week 6 | 
| Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6 | The Clinical Global Impression of Improvement Scale (CGI-I) will provide an overall clinician-determined summary measure that takes into account all available information including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-I consists of a 7-point scale that evaluates the change from initiation of treatment similar to the Clinical Global Impression of Severity Scale (CGI-S). This 7-point scale requires the clinician to assess how much the subject's illness has improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major Depressive Disorder, MIN-117