Clinical trial NCT02695472 (phase 2, status: unknown status)
Conditions: major depressive disorder
ICD codes: F33.0, F33.1, F33.9, F32.0, F32.1, F32.9, F33.40
Drugs: 80 milligrams nsi-189, placebo, 40 milligrams nsi-189
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. Subject has the ability to understand the purpose, potential benefits and risks of the
             study and to provide signed and dated informed consent, authorizing the use of
             protected health information in accordance with national and local Subject privacy
             regulations.

          2. Males and females 18 to 60 years of age, inclusive, at the time of informed consent.

          3. Diagnosis of major depressive disorder, recurrent, as per Diagnostic and Statistical
             Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical
             Interview for the Diagnostic and Statistical Manual specific for Clinical Trials.
             Their major depressive episode must be at least 8 weeks in duration and confirmed via
             Structured Clinical Interview for the Diagnostic and Statistical Manual mood module
             interview administered by a remote, independent raters, prior to the baseline visit.

          4. Montgomery-Asberg Depression Scale (MADRS) score of 20 or greater, at Screening and
             Baseline (MADRS score confirmed to be 20 or greater via remote SAFER interview by an
             independent rater prior to the baseline visit).

          5. The following applies to female Subjects: Non-pregnant, non-lactating females of
             childbearing potential are eligible as long as they agree to use a double barrier
             method of birth control from Screening until 3 months following discontinuation of IP.
             Women who are not of childbearing potential (bilateral oophorectomy, bilateral tubal
             ligation, hysterectomy, or post-menopausal for at least 1 year) will not require such
             parameters in order to be eligible.

          6. The following applies to male subjects: Male subjects with a female partner of
             childbearing potential will be required to use double barrier method of birth control
             or practice abstinence during this study and for 3 months following discontinuation of
             Investigational Product. Note: These requirements also apply for male subjects who
             have had a vasectomy.

          7. Body mass index (BMI) ≥19.5 and ≤38.0 kg/m2, at Screening. Bodyweight must be >50 kg.

          8. Of stable medical health, in the opinion of the Site Investigator, as determined by
             Investigator discretion (medical history, physical examination, vital signs, ECG, and
             clinical laboratory assessments).

        Exclusion Criteria:

          1. Clinically significant history or evidence of cardiovascular, respiratory, hepatic,
             renal, gastrointestinal, endocrine, neurological, immunological, or other major
             disease as determined by the Investigator or designee such that participation in the
             study would place subjects at increased risk for serious adverse events.

          2. History of cancer or malignancy within the last 5 years. Note: Subjects with basal or
             squamous cell carcinoma may be permitted into the study on a case by case basis.

          3. History of seizures; head trauma; or any clinically significant finding on the
             neurologic examination such that participation in the study would place subjects at
             increased risk for serious adverse events.

          4. Previous or current diagnosis of bipolar or schizoaffective disorder or psychotic
             disorder, or any psychotic symptoms during the current major depressive episode
             (according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition).

          5. Subjects who have a concurrent primary psychiatric diagnosis, diagnosed by Structured
             Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th
             edition, other than depression.

          6. Subjects with delirium, dementia, Parkinson's disease, or Huntington's disease.

          7. Subjects who have failed to respond to more than two antidepressant trials of adequate
             dose (as defined in Massachusetts General Hospital Antidepressant Treatment Response)
             and duration (at least 8 weeks in duration) during the current major depressive
             episode as determined by the local rater and confirmed by an independent, remote rater
             prior to the baseline visit.

          8. Subjects with clinically significant suicidal ideation and/or behavior currently as
             determined by the Site Investigator, such that participation in the study would place
             subjects at increased risk for serious adverse events.

          9. Subjects with any current homicidal ideation.

         10. Clinically significant abnormal clinical chemistry values, as determined by the Site
             Investigator, or any values for Alanine aminotransferase (ALT), Aspartate
             aminotransferase (AST), total bilirubin or creatinine that are 1.5 times above the
             upper limit of normal (ULN) and deemed clinically significant by the Site
             Investigator; any clinically significant values as determined by the Site Investigator
             for platelets or hemoglobin that are below the lower limit of normal (LLN); or any out
             of normal range values for white blood cells (WBC) deemed clinically significant by
             the Site Investigator.

         11. Clinically significant (as determined by the Investigator) 12-lead Electrocardiogram
             (ECG) abnormalities, including corrected QT interval using Bazett's correction method
             of >450 msec for males and >470 msec for females.

         12. Subjects with (current) severe Post-Traumatic Stress Disorder (PTSD), severe Obsessive
             Compulsive Disorder (OCD), severe binge eating disorder, or subjects with anorexia or
             bulimia nervosa active within the past three years.

         13. Subjects who plan to undergo elective invasive procedures/surgeries at any time during
             the study through End-of-study.

         14. Subjects taking excluded medications (See Appendix 1)..

         15. History of alcohol or drug-dependence or abuse by Diagnostic and Statistical Manual of
             Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview
             for the Diagnostic and Statistical Manual specific for Clinical Trials within 12
             months prior to Screening.

         16. Positive screening test or baseline test for drugs-of-abuse (cocaine, amphetamines,
             barbiturates, opiates, benzodiazepines, cannabinoids, phencyclidine). Note any
             positive test result(s) for benzodiazepine(s), opiates, or psychostimulants
             accompanied by confirmation of a prescription for a valid medical reason will be
             allowed.

         17. Positive serum β-human chorionic gonadotropin (β-HCG) test at Screening or positive
             urine pregnancy test at baseline that is consistent with pregnancy (females only).

         18. Donation or loss of whole blood >200 mL within 30 days prior to dosing or ≥500 mL
             within 56 days prior to dosing. Note: Blood taken for routine medical evaluations
             totaling less than 50 mL will be permitted.

         19. Females who are pregnant, lactating, or planning to become pregnant during the study.

         20. Does not tolerate venipuncture.

         21. Subjects who have had electroconvulsive therapy within the 6 months prior to
             Screening.

         22. Current enrollment in any other drug, biologic, device, or clinical study, or
             treatment with an Investigational Product or approved therapy for investigational use
             within 45 days (or 5 half-lives, whichever is longer) prior to Day 1 of
             Investigational Product administration.

         23. Any concurrent disease or condition that, in the opinion of the Investigator, would
             make the subject unsuitable for participation in the clinical study.

         24. Subject who, in the opinion of the Site Investigator, are unable to understand the
             protocol requirements, instructions and study-related restrictions, the nature, scope
             and possible consequences of the clinical study.

         25. Subject who, in the opinion of the Site Investigator, are unlikely to comply with the
             protocol requirements, instructions and study-related restrictions; e.g.,
             uncooperative attitude, inability to return for follow-up and improbability of
             completing the clinical study.