| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012271 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of MK-0952 37.5 mg daily over a 4-week treatment period in improving cognitive function in patients with mild-to-moderate AD as assessed by the 0-hour to 24-hour difference in Word List Learning-Selective Reminding (WLL-SR) Summary Score and the 2-hour to 24-hour correct response percentage difference in the Word List Learning-Delayed Recognition (WLL-DR) test of the Computerized Neuropsychological Test Battery (CNTB); 2) To evaluate the safety and tolerability of MK-0952 37.5 mg daily in patients with mild-to-moderate AD. |
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| E.2.2 | Secondary objectives of the trial |
| 1) To evaluate the efficacy of MK-0952 37.5 mg daily over a 4-week treatment period in improving cognitive function in patients with mild-to-moderate AD as measured by the total score from the 11 tasks of the Alzheimer’s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog); 2) To evaluate the efficacy of MK-0952 37.5 mg daily over a 4-week treatment period in improving cognitive function in patients with mild-to-moderate AD as measured by a Memory Summary Score (MSS) derived from the Route test result and the following CNTB memory test scores: Summary Score from WLL-SR (0-hour), Recall Retention Index from WLL-DRCall (2-hour), Recognition Retention Index from WLL-DR (2-hour), correct percentage from the VMEM test, 0- to 24-hour Summary Score difference from WLL-SR, and 2- to 24-hour correct response percentage difference from WLL-DR. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female (not of reproductive potential) ≥55 years old
2. Diagnosis of probable AD according to NINCDS-ADRDA criteria
3. MMSE between 18 and 26, inclusive
4. MHIS ≤ 4
5. Patient has a Global Clinical Dementia Rating (CDR) score of 1 or 2, or, if the Global CDR is 0.5, then the CDR Sum of Boxes is at least 3.5.
6. Any regularly used medications taken for prior conditions other than AD have been at a stable dose for four weeks prior to Screening Visit, unless otherwise specified
7. Patient, by investigator’s clinical impression, has adequate motor and sensory capacities (when corrected, if necessary) to perform neuropsychological testing
8. Patient has a reliable informant/caregiver (e.g., spouse, sibling, close friend) who consents to: accompany patient to all clinic visits; provide information to study investigator/staff via telephone contact. (NOTE: Every effort should be made to ensure that any information is provided by the same informant/caregiver for a given patient throughout the duration of the study), return for per-protocol follow-up visits and procedures, including in the event of discontinuation of study drug; and supervise administration of study medication.
9. Patient and caregiver/informant are fluent in written and verbal English.
10. Patient has a normal screening test for fecal occult blood; or, if the screening test for fecal occult blood is abnormal but likely due to hemorrhoids, the patient has had a normal sigmoidoscopy, rectoscopy, and/or colonoscopy within the last year prior to Screening Visit.
11. Patient performance on CNTB practice battery elicits a “YES” response on Pre-screen checklist for inclusion into the study.
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| E.4 | Principal exclusion criteria |
1. Patient is living in a nursing home or skilled nursing facility.
2. Patient has a history (within 2 years of Screening Visit) or current evidence of any neurological or neurodegenerative disorder, other than AD, that is associated with transient or sustained altered cognition or that may interfere with cognitive assessment, including, but not limited to, transient ischemic events, epilepsy, Parkinson’s disease, Dementia with Lewy Bodies, progressive supranuclear palsy, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, or significant head trauma with loss of consciousness.
3. Patient has a history of stroke or multiple lacunar infarcts.
4. Patient has a history (within 2 years prior to Screening Visit) or current evidence of a psychotic disorder or a major untreated depressive disorder. NOTE: Patients who are on stable doses of antidepressants (e.g., Selective Serotonin Re-uptake Inhibitors [SSRIs]) for ≥3 months prior to Screening Visit are eligible for entry.
5. In the opinion of the investigator, patient has uncontrolled hypertension or a history in the 2 years prior to Screening Visit of clinically significant cardiac arrhythmia, angina, or congestive heart failure with symptoms that occur at rest, or orthostatic symptoms.
6. Patient has a clinically significant history, in the opinion of the investigator, of gastrointestinal bleeding disease within the past 5 years prior to Screening Visit.
7. Patient has current evidence or history within past 5 years of Crohn’s disease, ulcerative colitis, proctitis, mesenteric arteritis or enteritis and/or unexplained diarrhea, bloody or mucoid stools documented by history, physical examination, x-ray or scans, and/or laboratory values.
8. Patient has a recent history (within 2 weeks of Screening Visit) of severe abdominal pain and/or persistent abdominal pain and/or loose stools for 48 hours or more.
9. Patient has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
10. Patient has a history within the past 5 years of syncope, vasovagal reactions, frequent lightheadedness or frequent dizziness when standing, or a decrease in systolic blood pressure of ≥20 mm Hg when standing compared to sitting/lying at Screening Visit.
11. Patient has any conduction delays, an abnormal QTc (>440 msec) on the ECG obtained at Screening Visit, or any other clinically significant ECG abnormalities (as determined by the investigator).
12. Patient has any additional clinically significant abnormalities, as determined by the investigator or from abnormalities specified within the protocol I/E criteria, in laboratory safety tests or physical examination at Screening Visit.
13. Patient has, <6 months prior to Screening Visit, initiated treatment with memantine, the cholinesterase inhibitors donepezil (ARICEPTTM, Eisai Co., Ltd.), rivastigmine (EXELONTM, Novartis Pharmaceuticals Corp.), or galantamine (RAZADYNETM, Janssen Pharmaceutical Products, L.P.), or any other symptomatic AD treatments, including those newly available; or patient has discontinued use of such medications <2 months prior to Screening Visit.
NOTE: Patients who are using memantine, donepezil, rivastigamine, galantamine, or any newly-available symptomatic AD treatments may participate in the study provided they have been on a stable dose for ≥6 months prior to Screening Visit. The dose should not be increased during the course of the study, but it may be decreased for tolerability issues.
14. Various concomitant therapy restrictions as specified in the protocol I/E criteria |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Mean change from baseline to week 4 for the 0- to 24-hour summary score difference in WLL-SR test of CNTB; OR
Mean change from baseline to week 4 for 2- to 24-hour correct response percentage difference in WLL-DR test of CNTB.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 10 |
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