A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients
| Autor: | John A. Bilello, Bradford C. Dickerson, Gustavo Kinrys, Linda M. Thurmond, Marlene P. Freeman, Bettina B. Hoeppner, David Mischoulon, K Johe, Larry Ereshefsky, Maurizio Fava, Martina Flynn, J Johnstone, L G Gertsik, Brett A. English, Nikos Makris |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Aminopyridines Placebo Biomarkers Pharmacological Piperazines law.invention 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Double-Blind Method Randomized controlled trial law Internal medicine medicine Humans Psychiatry Adverse effect Molecular Biology Psychiatric Status Rating Scales Depressive Disorder Major Dose-Response Relationship Drug Depression business.industry Area under the curve Middle Aged medicine.disease 030227 psychiatry Clinical trial Psychiatry and Mental health Treatment Outcome Tolerability Cohort Major depressive disorder Female Original Article Corrigendum business Selective Serotonin Reuptake Inhibitors 030217 neurology & neurosurgery |
| Zdroj: | Molecular Psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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