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

• Sponsor: Minerva Neurosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03446846
• Collaborator: (none)
• Enrollment: 360
• Locations: 47
• Arms: 3
• Actual Duration (Months): 20.5
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: MIN-117 5.0 mg; Drug: MIN-117 2.5 mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Sponsor also masked.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 30, 2018
• Actual Primary Completion Date: Nov 21, 2019
• Actual Study Completion Date: Dec 13, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [Week 6]

   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.

Secondary Outcome Measures

1. Change in Hamilton Anxiety Scale (HAM-A) [Change from Baseline to the end of Week 6]

   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.

2. Change in Clinical Global Impression of Severity Scale (CGI-S) [Change from Baseline to Week 6]

   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.

3. Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland International Research Group, LLC	Little Rock	Arkansas	United States	72211
2	Collaborative Neuroscience Network, LLC	Garden Grove	California	United States	92845
3	Collaborative Neuroscience Network, LLC	Torrance	California	United States	90502
4	Pacific Clinical Research Medical Group	Upland	California	United States	91786
5	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
6	Hassman Research Institute, LLC	Berlin	New Jersey	United States	08009
7	Neurobehavioral Research, Inc, Cedarhurst, NY	Cedarhurst	New York	United States	11516
8	Neuro-Behavorial Clinical Research Inc	Canton	Ohio	United States	44718
9	Oregon Center for Clinical Investigations	Portland	Oregon	United States	97214
10	FutureSearch Trials	Dallas	Texas	United States	75231
11	Mental Health Centre "Prof. Dr. Ivan-Temkov - Burgas" EOOD Complex Lazur	Burgas		Bulgaria
12	"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD, First psychiatric clinic	Pleven		Bulgaria
13	UMHAT "Sveti Georgi" EAD - Psychiatry Clinic	Plovdiv		Bulgaria
14	Mental Health Center, Ruse	Ruse		Bulgaria
15	"Diagnostic-Consultative Center St. Vrach and St. St. Kuzma and Damyan" OOD, Psychiatric office	Sofia		Bulgaria
16	"Medical Center Stimul" OOD, Psychiatric office	Sofia		Bulgaria
17	MC Intermedika	Sofia		Bulgaria
18	MC Sveti Naum, Sofia	Sofia		Bulgaria
19	DCC Mladost-M OOD	Varna		Bulgaria
20	Helsingin Psykiatripalvelu Oy at Mehilainen Clinic, Lääkärikeskus Mehiläinen	Helsinki		Finland
21	Oulu Mentalcare Oy	Oulu		Finland
22	Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori	Pori		Finland
23	Mentoria	Tampere		Finland
24	Center for Mental Health and Prevention of Addiction Ltd	Tbilisi		Georgia
25	Tbilisi Mental Health Center Ltd	Tbilisi		Georgia
26	Department of Psychiatry, Addiction and Medical Psychology	Chisinau		Moldova, Republic of
27	Podlaskie Centrum Psychogeriatrii	Białystok		Poland
28	Ośrodek Badań Klinicznych - Clinsante S.C.	Bydgoszcz		Poland
29	Zespół Opieki Zdrowotnej w Chełmnie, Poradnia Zdrowia Psychicznego	Chełmno		Poland
30	ISPL	Gdańsk		Poland
31	NZOZ Syntonia	Pruszcz Gdański		Poland
32	Prywatna Klinika Psychiatryczna Inventiva	Tuszyn		Poland
33	Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I.I.Mechnykov", Regional Center of Psychosomatic Disorders based on Psychoneurology	Dnipro		Ukraine
34	Municipal non-Profit enterprise "Carpathian Regional Mental	Ivano-Frankivsk		Ukraine
35	State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine" Department of Neuroses and Borderline States	Kharkiv		Ukraine
36	The Training and Research Medical Complex "The Clinic" otharkiv National Medical University	Kharkiv		Ukraine
37	Municipal non-profit enterprise "Kherson Regional Psychiatric Care Facility"	Kherson		Ukraine
38	Municipal Non-Profit Enterprise "Kirovohrad Regional Psychoneurological Hospital of Kirovohrad Regional Council	Kropyvnytskyi		Ukraine
39	Municipal enterprise "Heikiv Psychoneurological Hospital, Dnipropetrovsk Regional Council"	Kryvyy Rih		Ukraine
40	Kyiv Clinical Hospital on Railway Transport #1 of the branch "Health Center" of the joint-stock company "Ukrainian Railway"	Kyiv		Ukraine
41	Kyiv Regional Medical Incorporation Psychiatry Center of Novel Treatment and Rehabilitation of Psychotic Disorders	Kyiv		Ukraine
42	Municipal Institution of Kyiv Regional Council "Regional Psychiatric and Narcological Medical Association"	Kyiv		Ukraine
43	National Military-Medical Clinical Center Main Military	Kyiv		Ukraine
44	Municipal non-profit enterprise of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital"	Lviv		Ukraine
45	Municipal Non-Profit Enterprise "Odessa Regional Psychiatric Hospital # 2" "of Odessa Regional Council"	Odessa		Ukraine
46	Communal enterprise "Poltava Regional Clinical Psychiatric Hospital named O.F. Maltsev Poltava Regional Council"	Poltava		Ukraine
47	Municipal non-profit enterprise"Vinnytsya Regional Psychoneurological Hospital named Acad. O.I. Yushchenko of Vinnytsya Regional Council	Vinnytsya		Ukraine

Sponsors and Collaborators

• Minerva Neurosciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 20, 2018
• Statistical Analysis Plan - Dec 6, 2019

More Information

Publications

None provided.

• Responsible Party: Minerva Neurosciences
• ClinicalTrials.gov Identifier: NCT03446846
• Other Study ID Numbers: MIN-117C03
• First Posted: Feb 27, 2018
• Last Update Posted: Dec 17, 2020
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Minerva Neurosciences: Major Depressive Disorder; MIN-117
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose orally once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose orally once daily.	Placebo taken as two Placebo capsules as a single dose orally once daily.
Period Title: Overall Study
STARTED	90	92	178
COMPLETED	83	87	162
NOT COMPLETED	7	5	16

Baseline Characteristics

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo	Total
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose orally once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose orally once daily.	Placebo taken as two Placebo capsules as a single dose orally once daily.	Total of all reporting groups
Overall Participants	91	92	177	360
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	91 100%	92 100%	177 100%	360 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (11.5)	47 (12.7)	47 (12.5)	48 (12.3)
Sex: Female, Male (Count of Participants)
Female	62 68.1%	60 65.2%	136 76.8%	258 71.7%
Male	29 31.9%	32 34.8%	41 23.2%	102 28.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 1.1%	1 1.1%	1 0.6%	3 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	5 5.5%	4 4.3%	11 6.2%	20 5.6%
White	85 93.4%	87 94.6%	165 93.2%	337 93.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description	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.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

ITT population: all randomized patients who received at least 1 dose of study drug.

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose once daily.	Placebo taken as two Placebo capsules as a single dose once daily.
Measure Participants	70	76	149
Mean (Standard Deviation) [score on a scale]	-12 (9.2)	-12 (9.2)	-12 (9.2)

2. Secondary Outcome

Title	Change in Hamilton Anxiety Scale (HAM-A)
Description	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.
Time Frame	Change from Baseline to the end of Week 6

Outcome Measure Data

Analysis Population Description

ITT population: all randomized patients who received at least 1 dose of study drug.

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose once daily.	Placebo taken as two Placebo capsules as a single dose once daily.
Measure Participants	70	76	149
Mean (Standard Deviation) [score on a scale]	-12 (8.0)	-11 (9.1)	-11 (8.5)

3. Secondary Outcome

Title	Change in Clinical Global Impression of Severity Scale (CGI-S)
Description	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.
Time Frame	Change from Baseline to Week 6

Outcome Measure Data

Analysis Population Description

ITT population: all randomized patients who received at least 1 dose of study drug.

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose once daily.	Placebo taken as two Placebo capsules as a single dose once daily.
Measure Participants	70	76	149
Mean (Standard Deviation) [score on a scale]	-1 (1.3)	-1 (1.1)	-1 (1.2)

4. Secondary Outcome

Title	Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6
Description	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.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

ITT population: all randomized patients who received at least 1 dose of study drug.

Arm/Group Title	5.0 mg MIN-117	2.5 mg MIN-117	Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose once daily.	MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose once daily.	Placebo taken as two Placebo capsules as a single dose once daily.
Measure Participants	70	76	149
Mean (Standard Deviation) [score on a scale]	3 (1.0)	3 (1.2)	3 (1.1)

Adverse Events

Time Frame	Approximately up to 11 weeks
Adverse Event Reporting Description	The Safety Population is the population of all patients who receive at least 1 dose of study treatment. Patients in this population will be analyzed according to the treatment they received, regardless of which treatment they were randomly assigned. All safety and tolerability analyses will be based on this population and treatment assignment. Treatment-emergent adverse events were those that were reported on or after the initiation of the study drug.
Arm/Group Title	5.0 mg MIN-117		2.5 mg MIN-117		Placebo
Arm/Group Description	MIN-117 5.0 mg taken as two MIN-117 2.5 mg capsules as a single dose orally once daily.		MIN-117 2.5 mg taken as one MIN-117 2.5 mg capsule and one Placebo capsule as a single dose orally once daily.		Placebo taken as two Placebo capsules as a single dose orally once daily.
All Cause Mortality
	5.0 mg MIN-117		2.5 mg MIN-117		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/91 (0%)		0/92 (0%)		0/177 (0%)
Serious Adverse Events
	5.0 mg MIN-117		2.5 mg MIN-117		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/91 (0%)		1/92 (1.1%)		0/177 (0%)
Psychiatric disorders
Feeling guilty	0/91 (0%)	0	1/92 (1.1%)	1	0/177 (0%)	0
Major depression	0/91 (0%)	0	1/92 (1.1%)	1	0/177 (0%)	0
Suicidal ideation	0/91 (0%)	0	1/92 (1.1%)	1	0/177 (0%)	0
Other (Not Including Serious) Adverse Events
	5.0 mg MIN-117		2.5 mg MIN-117		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/91 (12.1%)		11/92 (12%)		13/177 (7.3%)
Nervous system disorders
Headache	11/91 (12.1%)		11/92 (12%)		13/177 (7.3%)

Limitations/Caveats

No notable study limitations were identified.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI agrees not to independently publish the results before the publication of the multi-center results. PI agrees to submit their proposed publication or presentation to Sponsor at least 2 months prior to disclosure. Sponsor may comment and may require deletion of trade secrets and proprietary or confidential information, other than study data.