Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to test the efficacy and safety of an investigational medication for improving symptoms of Alzheimer's Disease. Subjects will receive either active medication or placebo for 28 days. Tests of memory, concentration will be included. Safety will be monitored using routine clinical and laboratory tests.
Interventions
DRUGMK0249
MK0249 two (2) 2.5 mg capsules quaque die (qd) for 28 day treatment period.
DRUGComparator: Placebo (unspecified)
MK0249 two (2) 2.5 mg Pbo capsules qd for a 28 day treatment period
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or females * Age at least 55 years or older * Mild-to-moderate Alzheimer's Disease, with Mini Mental State Examination (MMSE) between 18 and 26, inclusive, Modified Hachinski Ischemic Scale (MHIS) score =/\<4, Global CDR score of 1 or 2, and who have a reliable informant/caregiver to accompany patient to all clinic visits * If using symptomatic Alzheimer's Disease treatments, patients must be on the medication for 3 months and on a STABLE DOSE for at least 2 months
Exclusion criteria
* Patients cannot be living in a skilled nursing facility * Patients cannot have poorly-controlled hypertension * Patients cannot have the following conditions within 6 months of screening: significant cardiovascular disorders, active major depressive disorder, gastroesophageal reflux disease (GERD), or clinically significant sleep disorder * Various concomitant therapy restrictions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Week 4 Change From Baseline in Computerized Neuropsychological Test Battery (CNTB): Short CNTB Summary Score. | Baseline and Week 4 | The CNTB was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the short CNTB summary score. The short CNTB summary score was scored as the mean score across 5 modules: Word List Learning-Selective Reminding, Word List Learning-Delayed Recall, Simple Reaction Time, Choice Reaction Time, and Visual Memory subtests. The short CNTB summary score ranges from 0 to 100, with higher scores (and positive changes from baseline) indicating better performance. |
| Week 4 Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): ADAS-Cog Total Score | Baseline and Week 4 | The ADAS-Cog, scored as the total score of 11 tasks including mazes was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the ADAS-Cog total score. The ADAS-Cog total score ranges from 0 to 70, with higher total scores indicating more impairment. Lower scores (and negative changes from Baseline) indicate better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Week 4 Change From Baseline in Cognition Summary Score (CSS) | Baseline and Week 4 | The CSS was used to evaluate cognitive function as measured by the mean change from Baseline to Week 4 in the CSS total score. The CSS was derived from the correct sequence percentage from the Route Test and 6 of the CNTB scores (the CSS was scored as the mean of the 7 scores). CSS scores can range from 0 to 100, higher scores (and positive changes from baseline) indicate better performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline: Short CNTB Summary Score. | Baseline | The CNTB was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the short CNTB summary score. The short CNTB summary score was scored as the mean score across 5 modules: Word List Learning-Selective Reminding, Word List Learning-Delayed Recall, Simple Reaction Time, Choice Reaction Time, and Visual Memory subtests. The short CNTB summary score ranges from 0 to 100, with higher scores (and positive changes from baseline) indicating better performance. |
| Baseline: ADAS-Cog Total Score | Baseline | The ADAS-Cog, scored as the total score of 11 tasks including mazes was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the ADAS-Cog total score. The ADAS-Cog total score ranges from 0 to 70, with higher total scores indicating more impairment. Lower scores (and negative changes from Baseline) indicate better performance. |
| Baseline: Cognition Summary Score (CSS) | Baseline | The CSS was used to evaluate cognitive function as measured by the mean change from Baseline to Week 4 in the CSS total score. The CSS was derived from the correct sequence percentage from the Route Test and 6 of the CNTB scores (the CSS was scored as the mean of the 7 scores). CSS scores can range from 0 to 100, higher scores (and positive changes from baseline) indicate better performance. |
Participant flow
Recruitment details
First Patient Dosed: 13 JAN 2007; Last Patient Last Treatment: 14 AUG 2008. 15 U.S. outpatient centers.
Pre-assignment details
At Visit 1, patients were assessed using the protocol inclusion and exclusion criteria, then, if deemed eligible, patients were randomized at Visit 3.
Participants by arm
| Arm | Count |
|---|---|
| MK0249 (5 mg) Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd). | 73 |
| Placebo Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd). | 71 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | sponsor decision (abnormal ECG @ screen) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MK0249 (5 mg) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 6.91 | 73.7 years STANDARD_DEVIATION 8.91 | 74.05 years STANDARD_DEVIATION 7.91 |
| Sex: Female, Male Female | 43 Participants | 36 Participants | 79 Participants |
| Sex: Female, Male Male | 30 Participants | 35 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 73 | 9 / 70 |
| serious Total, serious adverse events | 3 / 73 | 1 / 70 |
Outcome results
Primary
Week 4 Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): ADAS-Cog Total Score
The ADAS-Cog, scored as the total score of 11 tasks including mazes was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the ADAS-Cog total score. The ADAS-Cog total score ranges from 0 to 70, with higher total scores indicating more impairment. Lower scores (and negative changes from Baseline) indicate better performance.
Time frame: Baseline and Week 4
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Week 4 Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): ADAS-Cog Total Score | -1.42 units on a scale | Standard Error 0.5 |
| Placebo | Week 4 Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): ADAS-Cog Total Score | -1.17 units on a scale | Standard Error 0.49 |
Comparison: comparison at Week 4p-value: 0.716Mixed Models Analysis
Primary
Week 4 Change From Baseline in Computerized Neuropsychological Test Battery (CNTB): Short CNTB Summary Score.
The CNTB was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the short CNTB summary score. The short CNTB summary score was scored as the mean score across 5 modules: Word List Learning-Selective Reminding, Word List Learning-Delayed Recall, Simple Reaction Time, Choice Reaction Time, and Visual Memory subtests. The short CNTB summary score ranges from 0 to 100, with higher scores (and positive changes from baseline) indicating better performance.
Time frame: Baseline and Week 4
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Week 4 Change From Baseline in Computerized Neuropsychological Test Battery (CNTB): Short CNTB Summary Score. | 0.13 units on a scale | Standard Error 0.61 |
| Placebo | Week 4 Change From Baseline in Computerized Neuropsychological Test Battery (CNTB): Short CNTB Summary Score. | -0.76 units on a scale | Standard Error 0.57 |
Comparison: comparison at Week 4p-value: 0.283Mixed Models Analysis
Secondary
Week 4 Change From Baseline in Cognition Summary Score (CSS)
The CSS was used to evaluate cognitive function as measured by the mean change from Baseline to Week 4 in the CSS total score. The CSS was derived from the correct sequence percentage from the Route Test and 6 of the CNTB scores (the CSS was scored as the mean of the 7 scores). CSS scores can range from 0 to 100, higher scores (and positive changes from baseline) indicate better performance.
Time frame: Baseline and Week 4
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Week 4 Change From Baseline in Cognition Summary Score (CSS) | 1.19 units on a scale | Standard Error 0.75 |
| Placebo | Week 4 Change From Baseline in Cognition Summary Score (CSS) | -0.19 units on a scale | Standard Error 0.72 |
Comparison: comparison at week 4p-value: 0.18Mixed Models Analysis
Other Pre-specified
Baseline: ADAS-Cog Total Score
The ADAS-Cog, scored as the total score of 11 tasks including mazes was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the ADAS-Cog total score. The ADAS-Cog total score ranges from 0 to 70, with higher total scores indicating more impairment. Lower scores (and negative changes from Baseline) indicate better performance.
Time frame: Baseline
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Baseline: ADAS-Cog Total Score | 19.08 units on a scale | Standard Deviation 7.51 |
| Placebo | Baseline: ADAS-Cog Total Score | 18.42 units on a scale | Standard Deviation 7.32 |
Other Pre-specified
Baseline: Cognition Summary Score (CSS)
The CSS was used to evaluate cognitive function as measured by the mean change from Baseline to Week 4 in the CSS total score. The CSS was derived from the correct sequence percentage from the Route Test and 6 of the CNTB scores (the CSS was scored as the mean of the 7 scores). CSS scores can range from 0 to 100, higher scores (and positive changes from baseline) indicate better performance.
Time frame: Baseline
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Baseline: Cognition Summary Score (CSS) | 42.31 units on a scale | Standard Deviation 7.35 |
| Placebo | Baseline: Cognition Summary Score (CSS) | 43.79 units on a scale | Standard Deviation 7.32 |
Other Pre-specified
Baseline: Short CNTB Summary Score.
The CNTB was used to evaluate cognitive function, as measured by the mean change from Baseline to Week 4 in the short CNTB summary score. The short CNTB summary score was scored as the mean score across 5 modules: Word List Learning-Selective Reminding, Word List Learning-Delayed Recall, Simple Reaction Time, Choice Reaction Time, and Visual Memory subtests. The short CNTB summary score ranges from 0 to 100, with higher scores (and positive changes from baseline) indicating better performance.
Time frame: Baseline
Population: Full Analysis Set: All patients who were randomized, took at least one dose of study medication, and had at least one efficacy measurement at either Baseline, Week 2 or Week 4. Patients were counted in the treatment group to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK0249 (5 mg) | Baseline: Short CNTB Summary Score. | 35.98 units on a scale | Standard Deviation 5.72 |
| Placebo | Baseline: Short CNTB Summary Score. | 36.23 units on a scale | Standard Deviation 6.59 |