Details

Autor(en) / Beteiligte

• Fava, M
• Johe, K
• Ereshefsky, L
• Gertsik, L G
• English, B A
• Bilello, J A
• Thurmond, L M
• Johnstone, J
• Dickerson, B C
• Makris, N
• Hoeppner, B B
• Flynn, M
• Mischoulon, D
• Kinrys, G
• Freeman, M P

Titel

A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients

Ist Teil von

• Molecular psychiatry, 2016-10, Vol.21 (10), p.1372-1380

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. ( n =6) or placebo ( n =2), the second cohort 40 mg b.i.d. ( n =6) or placebo ( n =2), and the third cohort 40 mg t.i.d. ( n =6) or placebo ( n =2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4–20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions—Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.