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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00506077
First received: July 24, 2007
Last updated: August 18, 2014
Last verified: August 2014
Results First Received: October 13, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Paranoid Schizophrenia
Interventions: Drug: MK0249
Drug: Comparator: Placebo (unspecified)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First Patient Dosed: 11 February 2008; Last Patient Last Treatment: 08 October 2008. Six ex-U.S. study centers (3 Russia, 3 India).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At visit 1, patients were assessed using the protocol eligibility criteria. Eligible patients continued into an 8 day single-blind placebo washout/run-in period, and then were randomized at visit 3 to 1 of 2 cross-over treatment sequences.

Reporting Groups
  Description
MK0249 Then Placebo These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2.
Placebo Then MK0249 These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2.

Participant Flow for 3 periods

Period 1:   Treatment Period 1
    MK0249 Then Placebo     Placebo Then MK0249  
STARTED     28     27  
COMPLETED     24     24  
NOT COMPLETED     4     3  
Adverse Event                 2                 1  
Lost to Follow-up                 0                 2  
Withdrawal by Subject                 2                 0  

Period 2:   Washout
    MK0249 Then Placebo     Placebo Then MK0249  
STARTED     24     24  
COMPLETED     24     24  
NOT COMPLETED     0     0  

Period 3:   Treatment Period 2
    MK0249 Then Placebo     Placebo Then MK0249  
STARTED     24     24  
COMPLETED     23     23  
NOT COMPLETED     1     1  
Adverse Event                 0                 1  
Withdrawal by Subject                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
MK0249 Then Placebo These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2.
Placebo Then MK0249 These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2.
Total Total of all reporting groups

Baseline Measures
    MK0249 Then Placebo     Placebo Then MK0249     Total  
Number of Participants  
[units: participants]
  28     27     55  
Age  
[units: years]
Mean ± Standard Deviation
  30.7  ± 7.5     32.5  ± 8.4     31.6  ± 7.9  
Gender  
[units: participants]
     
Female     8     7     15  
Male     20     20     40  



  Outcome Measures
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1.  Primary:   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 ]

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

3.  Secondary:   Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score   [ Time Frame: Baseline and 4 weeks of treatment ]

4.  Secondary:   Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score   [ Time Frame: Baseline and 4 weeks of treatment ]
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Measure Type Secondary
Measure Title Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score
Measure Description 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.
Time Frame Baseline and 4 weeks of treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): The FAS included all randomized patients who took at lease one dose of study medication and had at least one post-randomization efficacy measurement in either of the two treatment periods. The data as observed (DAO) approach was used to handle missing data.

Reporting Groups
  Description
MK0249 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Placebo 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.

Measured Values
    MK0249     Placebo  
Number of Participants Analyzed  
[units: participants]
  44     43  
Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score  
[units: Composite┬áT-score]
Least Squares Mean ( 95% Confidence Interval )
  0.8  
  ( -1.0 to 2.6 )  
  -0.2  
  ( -2.0 to 1.5 )  


Statistical Analysis 1 for Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score
Groups [1] All groups
Method [2] constrained Logitudinal Data Analysis
P Value [3] 0.736
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The model factors were treatment, sequence, period, week (as categorical variable), site, treatment-by-week, sequence-by-week, and period-by-week.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The Benjamini & Hochberg False Discovery Rate (FDR) approach at critical value 0.05 was used among 1 primary and 3 secondary cognition efficacy endpoints to control the false positive rate.



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

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

7.  Other Pre-specified:   Pre-randomization Baseline: Episodic Memory Composite Score   [ Time Frame: Pre-randomization Baseline ]

8.  Other Pre-specified:   Pre-randomization Baseline: Working Memory Composite Score   [ Time Frame: Pre-randomization Baseline ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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