MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia (0249-016)

A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia

The purpose of this study is to determine the safety and effectiveness of an investigational drug MK0249 for the treatment of the cognitive impairment in patients with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Paranoid Schizophrenia
• Intervention / Treatment: Drug: MK0249; Drug: Comparator: Placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is clinically stable, on current antipsychotic medication for at least 3 months and current dose for 2 months
• Patient has a 6th grade reading level or better
• Females are not pregnant, and those who can have children agree to remain abstinent or use acceptable birth control throughout the study
• Patient has had a stable living arrangement for at least 3 months prior to study start
• Patient is in general good health based on screening assessments
• Patient has total Positive and Negative Syndrome Scale (PANSS) score between 36 and 75 at screening and at the first baseline visit
• Patient has a Clinical Global Impressions - Severity (CGI-S) score less than or equal to 4 at screening and at the first baseline visit

Exclusion Criteria:

• Patient has a major disease/disorder that may interfere with cognitive testing (such as mental retardation) and/or pose a risk upon study participation
• Patient has a history of head trauma with loss of consciousness greater than 15 minutes
• Patient has had warfarin treatment, MAO inhibitors, clonazepam or clozapine within 1 month of screening
• Patient has had ECT treatment within 6 months of screening
• Patient requires treatment with antihistamines or certain other medications listed in the protocol
• Patient has a history of liver disease that has been active within the last 2 years, or a history of cancer within the past 5 years
• Patient has a history of alcohol or drug dependence within the past year or alcohol or drug abuse within 3 months of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Comparator: Placebo (unspecified); MK0249 10mg (2 x 5 mg) Pbo tablet qd for a 28 day treatment period.
Experimental: MK0249	Drug: MK0249; MK0249 10mg (2 x 5 mg) tablet daily (qd) for 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	The mean change from baseline after 4 weeks of treatment in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.	Baseline and 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score	The Attention/Processing Speed Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Penn Continuous Performance Test (PCPT) and BACS battery Symbol Coding. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -91 and 91, respectively. Higher values (positive changes from baseline) indicate better performance.	Baseline and 4 weeks of treatment
Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score	The Episodic Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Face Memory and BACS battery Verbal Memory. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -202 and 202, respectively. Higher values (positive changes from baseline) indicate better performance.	Baseline and 4 weeks of treatment
Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score	The Working Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological (CNP) battery N-back test and the BACS battery Digit Sequencing test. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -122 and 122, respectively. Higher values (positive changes from baseline) indicate better performance.	Baseline and 4 weeks of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).	Pre-randomization Baseline
Pre-randomization Baseline: Attention/Processing Speed Composite Score	Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).	Pre-randomization Baseline
Pre-randomization Baseline: Episodic Memory Composite Score	Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).	Pre-randomization Baseline
Pre-randomization Baseline: Working Memory Composite Score	Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).	Pre-randomization Baseline

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• F Egan M, Zhao X, Gottwald R, Harper-Mozley L, Zhang Y, Snavely D, Lines C, Michelson D. Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment in patients with schizophrenia. Schizophr Res. 2013 May;146(1-3):224-30. doi: 10.1016/j.schres.2013.02.030. Epub 2013 Mar 22.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: July 24, 2007
• First Submitted That Met QC Criteria: July 24, 2007
• First Posted (Estimate): July 25, 2007

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 31, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Undifferentiated schizophrenia; residual schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction; Schizophrenia, Paranoid
• Other Study ID Numbers: 0249-016; 2007_522