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| ID | Type | Description | Link |
|---|---|---|---|
| 2007_522 |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK0249 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK0249 | Drug | MK0249 10mg (2 x 5 mg) tablet daily (qd) for 28 days. |
| |
| 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 |
| 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. |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23523692 | Derived | 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. |
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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.
First Patient Dosed: 11 February 2008; Last Patient Last Treatment: 08 October 2008. Six ex-U.S. study centers (3 Russia, 3 India).
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| ID | Title | Description |
|---|---|---|
| FG000 | MK0249 Then Placebo | These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2. |
| FG001 | Placebo Then MK0249 | These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| |||||||||||||||||||||
| Washout |
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| Treatment Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | MK0249 Then Placebo | These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2. |
| BG001 | Placebo Then MK0249 | These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Composite T-score | Baseline and 4 weeks of treatment |
|
Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up.
Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D012563 | Schizophrenia, Paranoid |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C574738 | MK-0249 |
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| Comparator: Placebo (unspecified) |
| Drug |
MK0249 10mg (2 x 5 mg) Pbo tablet qd for a 28 day treatment period. |
|
| 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 |
| 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 |
| Withdrawal by Subject |
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 |
| 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. |
| OG001 | 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. |
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Composite T-score | Baseline and 4 weeks of treatment |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Composite T-score | Baseline and 4 weeks of treatment |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Composite T-score | Baseline and 4 weeks of treatment |
|
|
|
|
| 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). | 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. | Posted | Least Squares Mean | Standard Error | Composite T-score | Pre-randomization Baseline |
|
|
|
| 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). | 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. | Posted | Least Squares Mean | Standard Error | Composite T-score | Pre-randomization Baseline |
|
|
|
| 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). | 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. | Posted | Least Squares Mean | Standard Error | Composite T-score | Pre-randomization Baseline |
|
|
|
| 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). | 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. | Posted | Least Squares Mean | Standard Error | Composite T-score | Pre-randomization Baseline |
|
|
|
| 0 |
| 52 |
| 20 |
| 52 |
| EG001 | 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. | 0 | 51 | 15 | 51 |
| irritability | General disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| nasopharyngitis | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
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| alanine aminotransferase increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
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| aspartate aminotransferase increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
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| blood creatine phosphokinase increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
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| blood creatinine increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
|
| blood urea increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
|
| eosinophil count increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
|
| lymphocyte count increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
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| neutrophil count decreased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
|
| platelet count increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
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| white blood cell count increased | Investigations | MedDRA (11.0) | Non-systematic Assessment |
|
| pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| headache | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| anxiety | Psychiatric disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| insomnia | Psychiatric disorders | MedDRA (11.0) | Non-systematic Assessment |
|
| middle insomnia | Psychiatric disorders | MedDRA (11.0) | Non-systematic Assessment |
|
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.