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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01520649
• Other study ID #: NS-2010-3
• Status: Completed
• Phase: Phase 1
• First received: January 25, 2012
• Last updated: April 1, 2014
• Start date: May 2012
• Est. completion date: February 2014

Study information

• Verified date: November 2012
• Source: Neuralstem Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. 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.

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 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.

4. Montgomery-Asberg Depression Scale (MADRS) score of 15 to 30, inclusive, at Screening and baseline.

5. 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.

6. The following applies to male subjects:

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• NSI-189 Phosphate
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).
• microcrystalline cellulose capsules
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).

Locations

Country	Name	City	State
United States	California Clinical Trials	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Neuralstem Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE,Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. PubMed PMID: 12813115. Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010 May;11(5):339-50. Epub 2010 Mar 31. Review. PubMed PMID: 20354534; PubMed Central PMCID: PMC2886712. DeCarolis NA, Eisch AJ. Hippocampal neurogenesis as a target for the treatment of mental illness: a critical evaluation. Neuropharmacology. 2010 May;58(6):884-93. Epub 2010 Jan 6. Review. PubMed PMID: 20060007; PubMed Central PMCID: PMC2839019. Marlatt MW, Lucassen PJ. Neurogenesis and Alzheimer's disease: Biology and pathophysiology in mice and men. Curr Alzheimer Res. 2010 Mar;7(2):113-25. Review.PubMed PMID: 19860727. Kernie SG, Parent JM. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis. 2010 Feb;37(2):267-74. Epub 2009 Nov 10. Review. PubMed PMID:19909815; PubMed Central PMCID: PMC2864918. Kempermann G, Krebs J, Fabel K. The contribution of failing adult hippocampalneurogenesis to psychiatric disorders. Curr Opin Psychiatry. 2008;21(3):290-5. PMID:18382230.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes