A Single-Center, Double-Blind (DB) Study of MEM 3454 on P50 Sensory Gating and Mismatch Negativity in Schizophrenia Patients (P50)

A Single-Center, Double-Blind, Placebo-Controlled, Randomized Blocks Study Investigating the Effect of 4 Dosages (1 mg, 5 mg, 15 mg, 50 mg) of MEM 3454 on P50 Sensory Gating and Mismatch Negativity (MMN) in Patients With Schizophrenia

The purpose of this study is to evaluate the effects of nicotinic alpha-7 MEM 3454 on P50 sensory gating in patients with Schizophrenia. The hypothesis is that MEM 3454 will normalize the P50 ratio.

Data produced in this study will provide useful information regarding the value of P50 as an efficacy biomarker, and provide evidence for the optimal dosing of MEM 3454 for additional P50 studies.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: MEM 3454; Drug: MEM 3454; Drug: MEM 3454; Drug: MEM 3454; Drug: Placebo for MEM 3454

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Male or female subjects between 18and 55 years of age.
• 2. Fluent in English, even if English is not the primary language.
• 3. Able to provide informed consent.
• 4. DSM IV-R primary diagnosis of schizophrenia (any subtype), assessed using a structured diagnostic interview (SCID CT).
• 5. Few or no extra-pyramidal symptoms(EPS)at screening,defined as SAS < 6.
• 6. Negative urine drug screen (UDS).
• 7. Negative cotinine test.
• 8. Clinically stable, as judged by the investigator, and in a non-acute phase for at least 12 weeks. At least one month on the same dose of antipsychotic medication.

Exclusion Criteria:

• Current risk of suicide, or history of suicidal behavior within the last 6 months.
• Hospitalized for psychiatric symptoms in the past 3 months.
• Other psychiatric diagnoses.
• Substance abuse/dependence (other than nicotine or caffeine) within the last 6 months according to the SCID-CT.
• Currently smoking, nicotine replacement therapy, smoking cessation medications or remedies, including Varenicline (Chantix).
• Any medical condition, as judged by the Investigator, which may interfere with the subjects' participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 1 mg dose	Drug: MEM 3454; 1 mg dose; Drug: MEM 3454; 5 mg dose; Drug: MEM 3454; 15 mg dose; Drug: MEM 3454; 50 mg dose
EXPERIMENTAL: 2; 5 mg dose	Drug: MEM 3454; 1 mg dose; Drug: MEM 3454; 5 mg dose; Drug: MEM 3454; 15 mg dose; Drug: MEM 3454; 50 mg dose
EXPERIMENTAL: 3; 15 mg dose	Drug: MEM 3454; 1 mg dose; Drug: MEM 3454; 5 mg dose; Drug: MEM 3454; 15 mg dose; Drug: MEM 3454; 50 mg dose
EXPERIMENTAL: 4; 50 mg dose	Drug: MEM 3454; 1 mg dose; Drug: MEM 3454; 5 mg dose; Drug: MEM 3454; 15 mg dose; Drug: MEM 3454; 50 mg dose
PLACEBO_COMPARATOR: 5; Placebo dose	Drug: Placebo for MEM 3454; Placebo dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the utility of P50 sensory gating as an efficacy biomarker for nicotinic alpha-7 agonist such as MEM 3454.	Pre-dosing and Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
• Investigate the safety and tolerability of MEM 3454 compared with placebo	all time points
• Determine whether MMN correlates with P50.	Pre-dose and day 1

Collaborators and Investigators

• Sponsor: Memory Pharmaceuticals
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Ann Olincy, MD, MPH, University of Colorado, Denver

Publications and helpful links

General Publications

• Braff DL, Light GA, Swerdlow NR. Prepulse inhibition and P50 suppression are both deficient but not correlated in schizophrenia patients. Biol Psychiatry. 2007 May 15;61(10):1204-7. doi: 10.1016/j.biopsych.2006.08.015. Epub 2006 Dec 8.
• Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R. Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006 Jun;63(6):630-8. doi: 10.1001/archpsyc.63.6.630.
• Simosky JK, Stevens KE, Freedman R. Nicotinic agonists and psychosis. Curr Drug Targets CNS Neurol Disord. 2002 Apr;1(2):149-62. doi: 10.2174/1568007024606168.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ANTICIPATED): March 1, 2009
• Study Completion (ANTICIPATED): April 1, 2009

Study Registration Dates

• First Submitted: July 29, 2008
• First Submitted That Met QC Criteria: July 30, 2008
• First Posted (ESTIMATE): July 31, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): July 31, 2008
• Last Update Submitted That Met QC Criteria: July 30, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: Schizophrenia; P50 Sensory Gating; Mismatched Negativity
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: MEM 3454-102