Multiple-Dose Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects

Study Overview
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Brief Summary
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This is a Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Escalation in depressed human subjects study.

Official Title
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A Phase 1B, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects

Conditions
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Depression

Intervention / Treatment
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* Drug: NSI-189 Phosphate
* Drug: microcrystalline cellulose capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has the ability to understand the purpose and risks of the study and to provide signed and dated informed consent, authorizing to use of protected health information in accordance with national and local patient privacy regulations. Males and females 18 to 60 years of age, inclusive, at the time of informed consent. Diagnosis of major depressive disorder, recurrent, as per DSM-IV-TR criteria and confirmed by SCID-CT. Their major depressive episode must be confirmed via SCID mood module interview administered by remote, independent raters. Note: Both patients who are being treated with antidepressants and patients who are not on antidepressants but had a history of taking antidepressants are permitted in the study. Montgomery-Asberg Depression Scale (MADRS) score of 15 to 30, inclusive, at Screening and baseline. The following applies to female patients:Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (hormonal contraception, abstinence, diaphragm with spermicide, condom with spermicide, or intrauterine device) from Screening until the end-of-study. The following applies to male subjects:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSI-189 Phosphate<br>There will be 3 ascending cohorts. The first cohort will be administered 40 mg once daily (q.d). The second cohort will be administered 40 mg twice daily (b.i.d). The third cohort will be administered 40 mg three times daily (t.i.d). | Drug: NSI-189 Phosphate<br>* The first cohort will be administered 40 mg once daily (q.d). The second cohort will be administered 40 mg twice daily (b.i.d). The third cohort will be administered 40 mg three times daily (t.i.d).<br>|
| Placebo Comparator: microcrystalline cellulose capsules<br>The first cohort will be administered 40 mg once daily (q.d). The second cohort will be administered 40 mg twice daily (b.i.d). The third cohort will be administered 40 mg three times daily (t.i.d). | Drug: microcrystalline cellulose capsules<br>* The first cohort will be administered 40 mg once daily (q.d). The second cohort will be administered 40 mg twice daily (b.i.d). The third cohort will be administered 40 mg three times daily (t.i.d).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of drug assessed by number and severity of adverse events in drug vs placebo group | Values for vital signs, standard physical examination, ECG, EEG, standard clinical laboratory tests (hematology and biochemistry), standard neurological exam and the Columbia Suicide Severity Rating Scale will be compared between NSI 189 and placebo. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of NSI 189 will be determined by plasma sample collection at various timepoints pre, during and post dosing, measuring the concentration of drug over time. | Concentration of NSI 189 will be measured in plasma and standard pK values will be determined:AUC, Cmax, Tmax, T1/2, CL, Vz. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurogenesis, hippocampal stem cells, depression, stroke