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

• ClinicalTrials.gov Identifier: NCT00506077
• Recruitment Status: Completed
• First Posted: July 25, 2007
• Results First Posted: March 7, 2011
• Last Update Posted: August 3, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Paranoid Schizophrenia	Drug: MK0249; Drug: Comparator: Placebo (unspecified)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: December 2007
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. [ Time Frame: Baseline and 4 weeks of treatment ]
   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.

Secondary Outcome Measures :

1. Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score [ Time Frame: Baseline and 4 weeks of treatment ]
   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.
2. Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score [ Time Frame: Baseline and 4 weeks of treatment ]
   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.
3. Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score [ Time Frame: Baseline and 4 weeks of treatment ]
   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.

Other Outcome Measures:

1. Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. [ Time Frame: Pre-randomization Baseline ]

   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).

2. Pre-randomization Baseline: Attention/Processing Speed Composite Score [ Time Frame: Pre-randomization Baseline ]

   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).

3. Pre-randomization Baseline: Episodic Memory Composite Score [ Time Frame: Pre-randomization Baseline ]

   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).

4. Pre-randomization Baseline: Working Memory Composite Score [ Time Frame: Pre-randomization Baseline ]

   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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00506077
• Other Study ID Numbers: 0249-016; 2007_522
• First Posted: July 25, 2007
• Results First Posted: March 7, 2011
• Last Update Posted: August 3, 2015
• Last Verified: July 2015

Keywords provided by Merck Sharp & Dohme Corp.:

Undifferentiated schizophrenia; residual schizophrenia

Additional relevant MeSH terms:

Schizophrenia; Cognitive Dysfunction; Schizophrenia, Paranoid; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders