A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, 2-Period Crossover Study to Assess the Efficacy and Safety of MK-0952 in Patients With Alzheimer’s Disease - MK-952 Proof of Concept Study

Phase 1

• Conditions: Alzheimer's Disease; MedDRA version: 8.0Level: LLTClassification code 10012271

• Registration Number: EUCTR2006-003924-13-GB
• Lead Sponsor: Merck Sharp & Dohme Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-12
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 76

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 d

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified