Single-Dose Pharmacokinetics (PK) Study of Novel Neurogenic Compound NSI-189

NCT01310881 | Completed Phase 1

• 1 other identifier: NS2010-2
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a subject single blinded, randomized, placebo-controlled, single dose, first-time-in-human study with three or more ascending cohorts.

Conditions

Depression

Keywords

Neurogenesis; hippocampal stem cells; depression; stroke

Outcome Measures

Primary Outcomes (1)

• Safety of drug assessed by number and severity of adverse events in drug vs placebo groups

  Values for vital signs, standard physical examination, ECG, EEG and standard clinical laboratory tests (haematology and biochemistry), and for standard neurological exam and the Columbia Suicide Severity Rating Scale will be compared between NS189 and placebo.

  7 days

Secondary Outcomes (1)

• Pharmacokinetics of NS189 will be determined by plasma sample collection at various timepoints post-dosing, and measuring concentration of drug over time.

  7 days

Study Arms (7)

Dose 1

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 2

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 3

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 4

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 5

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 6

EXPERIMENTAL

Drug: NSI-189 Phosphate

Dose 7

EXPERIMENTAL

Drug: NSI-189 Phosphate

Interventions

NSI-189 Phosphate DRUG

Once daily oral administration

Dose 1; Dose 2; Dose 3; Dose 4; Dose 5; Dose 6; Dose 7

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A subject must meet all of the following criteria:
• Subject has the ability to understand the purpose and risks of the study and to provide signed and dated informed consent.
• Males and females between 18 to 55 years of age, inclusive, at the time of informed consent.
• The following applies to female subjects:
• Non-childbearing potential (surgically sterile \[hysterectomy or bilateral tubal ligation\] or post-menopausal ≥ 1 year with follicle stimulating hormone \>40 U/L).
• The following applies to male subjects:
• Male subjects with a female partner of childbearing potential will be required to use an effective method of birth control or practice abstinence during this study and for 3 months following discontinuation of IMP.
• Non-smokers (or other nicotine use) as determined by history (no nicotine use over the past year) and by negative urine cotinine test at screening and Day -1.
• BMI ≥ 19.5 and ≤30.0 kg/m2, at screening. Bodyweight must be \>50 kg.
• Healthy, determined by pre-study medical evaluation and investigator discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory evaluations).

You may not qualify if:

• Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, dermatological or psychiatric disorder(s), or other major disease as determined by the Investigator or designee.
• History of seizures including febrile seizures, loss of consciousness, or any clinically significant finding on the neurologic examination.
• Clinically significant abnormal clinical chemistry values, as determined by the Investigator.
• Clinically significant (as determined by the Investigator) 12-lead ECG abnormalities, including corrected QT interval using Bazett's correction method of \>450 msec for males and \>470 msec for females.
• History of severe allergic or anaphylactic reactions.
• Subjects who have plans to undergo elective procedures/surgeries at any time during the study through the follow-up visits.
• A positive screening test for human immunodeficiency virus (HIV), hepatitis C virus antibody (HCVAb), hepatitis B core antibody (HBcAb), or hepatitis B surface antigen (HBsAg).
• Serious infection (e.g. pneumonia, septicemia) as determined by the Investigator within 3 months prior to Day -1.
• Fever or bacterial, or viral infection (including upper respiratory tract infection) within 2 weeks prior to Day -1.
• Treatment with any prescribed medication within 28 days prior to Day -1.
• Treatment with any over-the-counter products (OTC), including herbal and/or alternative health preparations and procedures within the 14 days prior to Day -1. Note: Intermittent treatment with acetaminophen \[≤1000 mg/day\] and/or ibuprofen \[≤400 mg/day\] is permitted.
• Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational product or approved therapy for investigational use within 30 days (or 5 half-lives, whichever is longer) prior to Day -1.
• Any live or attenuated immunization/vaccination within 1 month prior to the study drug administration or planned to occur during the study period.
• Donation of blood (\>500 mL) or blood products within 1 month prior to screening.
• History of alcohol or substance abuse (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, etc.) (as determined by the Investigator).

Sponsors & Collaborators

• Neuralstem Inc.: lead

Study Sites (1)

California Clinical Trials

Glendale, California, 91206, United States

Location

Related Publications (6)

• 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. doi: 10.1001/jama.289.23.3095.

  PMID: 12813115 BACKGROUND

• 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. doi: 10.1038/nrn2822. Epub 2010 Mar 31.

  PMID: 20354534 BACKGROUND

• 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. doi: 10.1016/j.neuropharm.2009.12.013. Epub 2010 Jan 6.

  PMID: 20060007 BACKGROUND

• 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. doi: 10.2174/156720510790691362.

  PMID: 19860727 BACKGROUND

• Kernie SG, Parent JM. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis. 2010 Feb;37(2):267-74. doi: 10.1016/j.nbd.2009.11.002. Epub 2009 Nov 10.

  PMID: 19909815 BACKGROUND

• Kempermann G, Krebs J, Fabel K. The contribution of failing adult hippocampal neurogenesis to psychiatric disorders. Curr Opin Psychiatry. 2008 May;21(3):290-5. doi: 10.1097/YCO.0b013e3282fad375.

  PMID: 18382230 BACKGROUND

MeSH Terms

Conditions

Depression; Stroke

Interventions

NSI-189

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Karl Johe, PhD

  Neuralstem Inc.

  STUDY DIRECTOR

• David Han, MD

  California Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2011
• First Posted: March 9, 2011
• Study Start: February 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: November 21, 2011

Record last verified: 2011-05

Locations

US (1)