E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of MIN-117 0.5 mg and 2.5 mg compared to placebo in reducing the symptoms of a major depressive episode as measured by the change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score over 6 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the efficacy of MIN-117 0.5 mg and 2.5 mg compared to placebo in onset of antidepressant response as measured by the change from Baseline in the MADRS total score over 6 weeks of treatment. · To assess the effects of MIN-117 compared to placebo on severity of illness and improvement using the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) over 6 weeks of treatment. · To assess the effect of MIN-117 compared to placebo on sexual functioning using the Arizona Sexual Experiences Scale (A-SEX). · To assess the effect of MIN-117 compared to placebo on executive function and working memory using Digit-Symbol Substitution Test (DSST), Towers of London Test, and Digit Span Backwards task. · To evaluate the safety and tolerability of MIN-117 compared to placebo over 6 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must be able to read and understand the consent forms, complete studyrelated procedures, and communicate with the study staff. 2. Subjects must have provided written consent to participate in the study and understand that they are free to withdraw from the study at any time. 3. Male or female subjects must be 18 to 65 years of age, inclusive, at Screening (Visit 1). 4. Subjects have a body mass index (BMI) of ≥ 18 to ≤ 35 kg/m2 [BMI = weight (kg)/height (m2)] at Screening (Visit 1) 5. Subjects must meet Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5) criteria for diagnosis of moderate or severe depression without psychotic features (ICD-9 codes 296.32 & 296.33; ICD-10 codes F33.1 & F33.2, respectively) at Screening based on clinical assessment and on the MINI, v7.0. 6. Subjects have a history of at least one previous episode of depression prior to the current episode. 7. Current major depressive episode of at least 8 weeks in duration. 8. Subjects must have a score of ≥ 30 on the investigator-rated MADRS at Screening (Visit 1) and Baseline (Visit 2a). 9. Subjects must have a score of ≥ 4 on the investigator-rated CGI-S at Screening (Visit 1) and Baseline (Visit 2a). 10. Subjects 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, blood chemistry, hematology, urinalysis, and electrocardiogram (ECG) 11. Female subjects must be postmenopausal, have had a hysterectomy or tubal ligation or be otherwise incapable of pregnancy, or must agree to consistent use of contraception for the duration of the study (oral or parenteral hormonal contraceptive or intrauterine device or barrier plus spermicide). |
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E.4 | Principal exclusion criteria |
1. A DSM-5 diagnosis of current (active) obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), anorexia nervosa, or bulimia nervosa. 2. Significant past or present neurological or neurosurgical disorder that could interfere with the study assessments (including but not limited to stroke, central nervous system [CNS]-related tumors, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, seizure disorder requiring current anticonvulsants, history of brain injury or trauma, or neurosyphilis). 3. History or current diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, mental retardation, or cluster B personality disorders, mood disorder with postpartum onset, somatoform disorders, chronic fatigue syndrome, or fibromyalgia. 4. Meeting DSM-5 criteria for substance abuse (alcohol or drugs) within 12 months prior to Screening Visit or substance dependence (except nicotine and caffeine) within 6 months prior to the Screening Visit or positive test for drugs of abuse. 5. Moderate or high risk of violent behavior or suicide as assessed by any history of suicide attempt, or a score of > 4 on MADRS item 10. 6. History of inadequate treatment response on 2 or more occasions of treatment with approved antidepressants (paroxetine included) as defined by failure to improve when treated with a licensed dose for an adequate duration. 7. History of treatment with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve simulation (VNS), or any related neuromodulator therapy within 6 months prior to the Screening Visit, including light therapy. 8. Subjects who, in the opinion of the investigator, should not discontinue, or participate in washout of a prohibited concomitant medication. 9. Receiving psychological treatments (e.g., cognitive behavior therapy, interpersonal psychotherapy, or psychodynamic psychotherapy) other than psychoeducational within 1 week prior to Baseline Visit randomization) that has not remained constant for at least 3 months, or that may change during this study. 10. Significant past or present metabolic, hepatic (including > 3X upper limit of normal [ULN] in liver function test at Screening and Baseline), renal, hematological, pulmonary, cardiovascular, metabolic, gastrointestinal, or urological disorder. 11. Any history of drug or other significant allergy or known hypersensitivity to any of the study drugs. 12. History of malignant disease within the past 5 years with the exception of minor superficial skin diseases (i.e., basal cell carcinoma and squamous cell carcinoma). 13. 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. 14. Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for at least 3 months prior to Screening (a normal thyroid-stimulating hormone [TSH] is required at sScreening). 15. Pregnant or breast-feeding female. 17. Positive hepatitis B surface antigen (HBsAg), or hepatitis C antibody, or human immunodeficiency virus (HIV) 1 and 2 antibodies at Screening. 18. Subjects with a clinically significant electrocardiogram (ECG) abnormality at Screening or Baseline visits that could be a safety issue in the study, including QT interval value corrected for heart rate using the Fridericia’s formula (QTcF) > 430 msec for males and > 450 msec for females. 19. 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. 20. No legal capacity or limited legal capacity or unable to give an informed consent. 21. Subjects unlikely to cooperate in the study, and/or poor compliance anticipated by the investigator.
The most important exlusion criteria listed above have the same numbers as in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from Baseline to Week 6 in MADRS mean total score will be used as the primary endpoint. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The change in MADRS: from Baseline to Week 6.
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E.5.2 | Secondary end point(s) |
1. The change in CGI-S and CGI-I 2. Change from Baseline in MADRS total score over 2 weeks of treatment 3. Change from baseline in cognition and sexual function 4. The rate of responders defined as a decrease in MADRS score of ≥ 50%. 5. Time to clinical response (first assessment with a ≥ 50% improvement from Baseline in total MADRS score scale) 6. The rate of early and sustained full responders (≥ 50% improvement from Baseline in total MADRS score and a CGI-I score ≤ 2 at every time points) and the rate of remission in MADRS (defined as a score < 12)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from baseline to week 6 2. Change in MADRS total score from baseline to Week 2 3. Changes in cognition and A-SEX from baseline to Week 6 4. at Week 1, 2, 4 and 6 5. from baseline to week 6 6. from baseline to Week 6
Timepoints of evaluation of endpoints numbered in this section as 1-6 are referring to secondary endpoints listed in section E.5.2 respectively. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |