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

Inclusion Criteria:

• Participants must be able to read and understand the consent forms, completestudy-related procedures, and communicate with the study staff.
• Participants must have provided written consent to participate in the study andunderstand that they are free to withdraw from the study at any time.
• Participants must have signed the informed consent form for pharmacogenomic researchindicating willingness to participate in the pharmacogenomic component of the study inorder to participate in the optional pharmacogenomic component of this study. Refusalto consent for this component does not exclude a participant from participation in theclinical 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 distressand without psychotic features at Screening based on clinical assessment and on theStructured Clinical Interview for DSM-5 (SCID-5). Their major depressive episode mustbe 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 tothe current episode.
• Participant must have been treated with an antidepressant administered at an adequatedose and duration in the past for the treatment of Major Depression. An adequatetreatment is defined as an antidepressant treatment for at least 4 weeks at at leastthe 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 onthe patient rated Inventory of Depressive Symptoms self-report (IDS-SR30).
• At Screening (Visit 1) and Baseline (Visit 2), participants must have a score ≥ 18 onHamilton Anxiety Scale (HAM-A).
• At Screening (Visit 1) and Baseline (Visit 2), participants must have a score ≥ 4 onthe 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 noclinically 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:

1. be post-menopausal, or
2. have had a hysterectomy or tubal ligation or be otherwise incapable of pregnancy,or
3. must agree to consistent use of 2 methods of contraception for the duration ofthe study and until 90 days after the last dose of study medication.

• Female participants of childbearing potential must have a negative serum pregnancytest 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, mentalretardation, 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), VagusNerve Stimulation (VNS), Deep Brain Stimulation (DBS), or Transcranial MagneticStimulation (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 depressivesymptoms as reflected by the IDS-SR30 total score from Screening visit to Baselinevisit.
• Active cardiovascular disease (including but not limited to: atrial fibrillation orflutter, second and third-degree atrioventricular heart block, restingsupraventricular tachycardia > 100 beats per minute, unstable ischemic heart disease,valvular abnormality, sick sinus syndrome or other condition requiring pacemaker) ordiastolic 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 studyassessments (including by not limited to: stroke, tumor, multiple sclerosis,Parkinson's disease, Alzheimer's disease, Huntington's disease, seizure disorderrequiring current anti-convulsants, traumatic brain injury or trauma, andneurosyphilis.
• Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for atleast 3 months prior to Screening (a normal thyroid-stimulating hormone [TSH] isrequired 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) ofthe study drug.
• History of alcohol or substance use disorders (except nicotine and caffeine) meetingDSM-5 criteria within 1-year prior to Screening visit.
• Positive alcohol and urine drug screen for opiates, cocaine, barbiturates,tetrahydrocannabinol, methadone, tricyclic antidepressants, benzodiazepines, andamphetamine/methamphetamine at Screening or Baseline. Patients with positive testingat 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 daysbefore the planned start of treatment (Day 1) or have participated in 2 or moreclinical trials in the previous 2 years.
• QT interval corrected with Fridericia's formula (QTcF) at Screening or Baselinegreater than 450 msec for males and 470 msec for females.
• Positive hepatitis B surface antigen, or hepatitis C antibody or HumanImmunodeficiency Virus (HIV) 1 and 2 antibodies at Screening.
• Employees of the investigator or study center, when the employee has directinvolvement in the proposed study or other studies under the direction of thatinvestigator or study center; also family members of the employee or the investigator.