Clinical trial NCT03446846: A Study to Evaluate the Efficacy and Safety of MIN-117 in Adult Patients With Major Depressive Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
MIN-117
Lead sponsor: Minerva Neurosciences
Sponsor class: INDUSTRY
First posted: 2018-02-27
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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.

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Week 6
Secondary outcomes:
measure: Change in Hamilton Anxiety Scale (HAM-A)
timeFrame: Change from Baseline to the end of Week 6
measure: Change in Clinical Global Impression of Severity Scale (CGI-S)
timeFrame: Change from Baseline to Week 6
measure: Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6
timeFrame: Week 6
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Berlin
country: United States
facility: Hassman Research Institute, LLC
state: New Jersey
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc, Cedarhurst, NY
state: New York
city: Canton
country: United States
facility: Neuro-Behavorial Clinical Research Inc
state: Ohio
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations
state: Oregon
city: Dallas
country: United States
facility: FutureSearch Trials
state: Texas
city: Burgas
country: Bulgaria
facility: Mental Health Centre "Prof. Dr. Ivan-Temkov - Burgas" EOOD Complex Lazur
city: Pleven
country: Bulgaria
facility: "University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD, First psychiatric clinic
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi" EAD - Psychiatry Clinic
city: Ruse
country: Bulgaria
facility: Mental Health Center, Ruse
city: Sofia
country: Bulgaria
facility: "Diagnostic-Consultative Center St. Vrach and St. St. Kuzma and Damyan" OOD, Psychiatric office
city: Sofia
country: Bulgaria
facility: "Medical Center Stimul" OOD, Psychiatric office
city: Sofia
country: Bulgaria
facility: MC Intermedika
city: Sofia
country: Bulgaria
facility: MC Sveti Naum, Sofia
city: Varna
country: Bulgaria
facility: DCC Mladost-M OOD
city: Helsinki
country: Finland
facility: Helsingin Psykiatripalvelu Oy at Mehilainen Clinic, Lääkärikeskus Mehiläinen
city: Oulu
country: Finland
facility: Oulu Mentalcare Oy
city: Pori
country: Finland
facility: Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori
city: Tampere
country: Finland
facility: Mentoria
city: Tbilisi
country: Georgia
facility: Center for Mental Health and Prevention of Addiction Ltd
city: Tbilisi
country: Georgia
facility: Tbilisi Mental Health Center Ltd
city: Chisinau
country: Moldova, Republic of
facility: Department of Psychiatry, Addiction and Medical Psychology
city: Białystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: Ośrodek Badań Klinicznych - Clinsante S.C.
city: Chełmno
country: Poland
facility: Zespół Opieki Zdrowotnej w Chełmnie, Poradnia Zdrowia Psychicznego
city: Gdańsk
country: Poland
facility: ISPL
city: Pruszcz Gdański
country: Poland
facility: NZOZ Syntonia
city: Tuszyn
country: Poland
facility: Prywatna Klinika Psychiatryczna Inventiva
city: Dnipro
country: Ukraine
facility: Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I.I.Mechnykov", Regional Center of Psychosomatic Disorders based on Psychoneurology
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal non-Profit enterprise "Carpathian Regional Mental
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine" Department of Neuroses and Borderline States
city: Kharkiv
country: Ukraine
facility: The Training and Research Medical Complex "The Clinic" otharkiv National Medical University
city: Kherson
country: Ukraine
facility: Municipal non-profit enterprise "Kherson Regional Psychiatric Care Facility"
city: Kropyvnytskyi
country: Ukraine
facility: Municipal Non-Profit Enterprise "Kirovohrad Regional Psychoneurological Hospital of Kirovohrad Regional Council
city: Kryvyy Rih
country: Ukraine
facility: Municipal enterprise "Heikiv Psychoneurological Hospital, Dnipropetrovsk Regional Council"
city: Kyiv
country: Ukraine
facility: Kyiv Clinical Hospital on Railway Transport #1 of the branch "Health Center" of the joint-stock company "Ukrainian Railway"
city: Kyiv
country: Ukraine
facility: Kyiv Regional Medical Incorporation Psychiatry Center of Novel Treatment and Rehabilitation of Psychotic Disorders
city: Kyiv
country: Ukraine
facility: Municipal Institution of Kyiv Regional Council "Regional Psychiatric and Narcological Medical Association"
city: Kyiv
country: Ukraine
facility: National Military-Medical Clinical Center Main Military
city: Lviv
country: Ukraine
facility: Municipal non-profit enterprise of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital"
city: Odessa
country: Ukraine
facility: Municipal Non-Profit Enterprise "Odessa Regional Psychiatric Hospital # 2" "of Odessa Regional Council"
city: Poltava
country: Ukraine
facility: Communal enterprise "Poltava Regional Clinical Psychiatric Hospital named O.F. Maltsev Poltava Regional Council"
city: Vinnytsya
country: Ukraine
facility: Municipal non-profit enterprise"Vinnytsya Regional Psychoneurological Hospital named Acad. O.I. Yushchenko of Vinnytsya Regional Council
Study officials:
References: