Paranoid Schizophrenia
Conditions
Keywords
Undifferentiated schizophrenia, residual schizophrenia
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.
Interventions
DRUGMK0249
MK0249 10mg (2 x 5 mg) tablet daily (qd) for 28 days.
DRUGComparator: Placebo (unspecified)
MK0249 10mg (2 x 5 mg) Pbo tablet qd for a 28 day treatment period.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score | 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. |
| Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score | 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. |
| Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score | 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
| Measure | Time frame | Description |
|---|---|---|
| Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 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). |
| Pre-randomization Baseline: Attention/Processing Speed Composite Score | 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). |
| Pre-randomization Baseline: Episodic Memory Composite Score | 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). |
| Pre-randomization Baseline: Working Memory Composite Score | 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). |
Participant flow
Recruitment details
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
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.
Participants by arm
| Arm | Count |
|---|---|
| MK0249 Then Placebo These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2. | 28 |
| Placebo Then MK0249 These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2. | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 2 | 1 |
| Treatment Period 1 | Lost to Follow-up | 0 | 2 |
| Treatment Period 1 | Withdrawal by Subject | 2 | 0 |
| Treatment Period 2 | Adverse Event | 0 | 1 |
| Treatment Period 2 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MK0249 Then Placebo | Placebo Then MK0249 | Total |
|---|---|---|---|
| Age, Continuous | 30.7 years STANDARD_DEVIATION 7.5 | 32.5 years STANDARD_DEVIATION 8.4 | 31.6 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 52 | 15 / 51 |
| serious Total, serious adverse events | 0 / 52 | 0 / 51 |
Outcome results
Primary
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.
Time frame: Baseline and 4 weeks of treatment
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0249 | Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 0.4 Composite T-score |
| Placebo | Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 0.5 Composite T-score |
p-value: 0.939constrained longitudinal data analysis
Secondary
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.
Time frame: Baseline and 4 weeks of treatment
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0249 | Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score | 0.5 Composite T-score |
| Placebo | Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score | 0.0 Composite T-score |
p-value: 0.736constrained Longitudinal Data Analysis
Secondary
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.
Time frame: Baseline and 4 weeks of treatment
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0249 | Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score | 0.9 Composite T-score |
| Placebo | Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score | 0.1 Composite T-score |
p-value: 0.736constrained Longitudinal Data Analysis
Secondary
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.
Time frame: Baseline and 4 weeks of treatment
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0249 | Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score | 0.8 Composite T-score |
| Placebo | Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score | -0.2 Composite T-score |
p-value: 0.736constrained Logitudinal Data Analysis
Other Pre-specified
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).
Time frame: Pre-randomization Baseline
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK0249 | Pre-randomization Baseline: Attention/Processing Speed Composite Score | 47.8 Composite T-score | Standard Error 0.73 |
| Placebo | Pre-randomization Baseline: Attention/Processing Speed Composite Score | 47.8 Composite T-score | Standard Error 0.73 |
Other Pre-specified
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).
Time frame: Pre-randomization Baseline
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK0249 | Pre-randomization Baseline: Episodic Memory Composite Score | 43.9 Composite T-score | Standard Error 1.16 |
| Placebo | Pre-randomization Baseline: Episodic Memory Composite Score | 43.9 Composite T-score | Standard Error 1.16 |
Other Pre-specified
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).
Time frame: Pre-randomization Baseline
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK0249 | Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 40.5 Composite T-score | Standard Error 0.98 |
| Placebo | Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. | 40.5 Composite T-score | Standard Error 0.98 |
Other Pre-specified
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).
Time frame: Pre-randomization Baseline
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK0249 | Pre-randomization Baseline: Working Memory Composite Score | 43.5 Composite T-score | Standard Error 0.98 |
| Placebo | Pre-randomization Baseline: Working Memory Composite Score | 43.5 Composite T-score | Standard Error 0.98 |