Trial Outcomes & Findings for MK0249 for the Symptomatic Treatment of Alzheimer's Disease (MK0249-011) (NCT NCT00420420)

NCT ID: NCT00420420

Last Updated: 2015-02-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

144 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2015-02-12

Participant Flow

First Patient Dosed: 13 JAN 2007; Last Patient Last Treatment: 14 AUG 2008. 15 U.S. outpatient centers.

At Visit 1, patients were assessed using the protocol inclusion and exclusion criteria, then, if deemed eligible, patients were randomized at Visit 3.

Participant milestones

Participant milestones
Measure	MK0249 (5 mg) Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Overall Study STARTED	73	71
Overall Study COMPLETED	65	67
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	MK0249 (5 mg) Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Overall Study Adverse Event	5	3
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	1	0
Overall Study sponsor decision (abnormal ECG @ screen)	1	0

Baseline Characteristics

MK0249 for the Symptomatic Treatment of Alzheimer's Disease (MK0249-011)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK0249 (5 mg) n=73 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=71 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).	Total n=144 Participants Total of all reporting groups
Age, Continuous	74.4 years STANDARD_DEVIATION 6.91 • n=5 Participants	73.7 years STANDARD_DEVIATION 8.91 • n=7 Participants	74.05 years STANDARD_DEVIATION 7.91 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	36 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	35 Participants n=7 Participants	65 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=59 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=62 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
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	-0.76 units on a scale Standard Error 0.57

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=70 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=68 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
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 0.50	-1.17 units on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=49 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=51 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Week 4 Change From Baseline in Cognition Summary Score (CSS)	1.19 units on a scale Standard Error 0.75	-0.19 units on a scale Standard Error 0.72

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=64 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=68 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Baseline: Short CNTB Summary Score.	35.98 units on a scale Standard Deviation 5.72	36.23 units on a scale Standard Deviation 6.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=73 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=70 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Baseline: ADAS-Cog Total Score	19.08 units on a scale Standard Deviation 7.51	18.42 units on a scale Standard Deviation 7.32

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	MK0249 (5 mg) n=56 Participants Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=57 Participants Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Baseline: Cognition Summary Score (CSS)	42.31 units on a scale Standard Deviation 7.35	43.79 units on a scale Standard Deviation 7.32

Adverse Events

MK0249 (5 mg)

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK0249 (5 mg) n=73 participants at risk Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=70 participants at risk Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Injury, poisoning and procedural complications Accidental Overdose	0.00% 0/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	1.4% 1/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Injury, poisoning and procedural complications Hip fracture	1.4% 1/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.4% 1/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Respiratory, thoracic and mediastinal disorders Lung infiltration	1.4% 1/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK0249 (5 mg) n=73 participants at risk Patients were randomly assigned to 28 days of treatment with 5 mg MK-0249 taken orally daily (qd).	Placebo n=70 participants at risk Patients were randomly assigned to 28 days of treatment with matching placebo taken orally daily (qd).
Gastrointestinal disorders Diarrhoea	8.2% 6/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	2.9% 2/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Gastrointestinal disorders Dry mouth	4.1% 3/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Gastrointestinal disorders Dyspepsia	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Gastrointestinal disorders Nausea	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	2.9% 2/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Gastrointestinal disorders Stomach discomfort	5.5% 4/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Gastrointestinal disorders Vomiting	4.1% 3/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Infections and infestations Nasopharyngitis	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	1.4% 1/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Infections and infestations Urinary tract infection	4.1% 3/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	2.9% 2/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Injury, poisoning and procedural complications Excoriation	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Injury, poisoning and procedural complications Fall	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	4.3% 3/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Investigations Electrocardiogram QT prolonged	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Musculoskeletal and connective tissue disorders Muscle spasms	5.5% 4/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Nervous system disorders Dizziness	2.7% 2/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	1.4% 1/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Nervous system disorders Headache	8.2% 6/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	1.4% 1/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.
Psychiatric disorders Insomnia	5.5% 4/73 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.	0.00% 0/70 • Patients were assessed for AEs from Visit 2 (Day 0) Baseline through Visit 8 (Day 43) Post-Study Safety Visit.