Clinical trial NCT01181310: Placebo-Controlled Crossover Study to Evaluate Donepezil and MK-3134 for Reversal of Cognitive Impairment Associated With Scopolamine Administration (3134-005)(COMPLETED)
Official title: A Five-Period, Placebo-Controlled, Crossover Study to Evaluate the Effect of Donepezil and MK-3134 on Reversal of Cognitive Impairment Associated With a Single-Dose of Scopolamine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dementia
Keywords: dementia, cognitive impairment, neurodegeneration, Alzheimer's, acetylcholine, AchE
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-08-13
Enrollment: 31
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The drug, scopolamine, can result in short-term impairments of cognitive function, attention, and memory that resemble those seen in aging and Alzheimer's disease. This study tested the capability of both individual and combined doses of MK-3134 and the current standard treatment: donepezil (Aricept), to reverse such impairments, following a single dose of scopolamine. Participants were evaluated after each of 5 different treatment periods (in a cross-over, double-dummy design): A: placebo to match both donepezil (oral \[PO\]) and MK-3134 (PO) followed by placebo scopolamine (subcutaneous \[SQ\]); B: placebo to match both donepezil (PO) and MK-3134 (PO), followed by scopolamine SQ; C: MK-3134 (PO) followed by scopolamine SQ; D: donepezil (PO) followed by scopolamine SQ; E: MK-3134 (PO) and donepezil (PO) followed by scopolamine SQ. The doses of MK3134, donepezil, and scopolamine were the same over all treatment arms in which the specified drug was administered. There were 8 total visits for each treatment period, including 5 Treatment Visits requiring 14-day intervals between visits for study-drug washout. Participants were assessed for cognitive function before and after each treatment period during the Treatment Visits.


Eligibility criteria: Participants were eligible for inclusion in the study who were:

* Male between 18 and 40 years of age.
* Non-smokers, in good health (as defined in protocol), and were willing to follow study-related procedures.

Participants were not eligible for inclusion in the study if they:

* Had a history of illness that, in the opinion of the study investigator or as specified in protocol, might confound the results of the study or posed an potential, additional risk to the participant if they were to participate in the study.
* Were taking any medication (prescription, nonprescription, vitamin supplements or herbal, illicit or legitimate) except for acetaminophen.
* Had a history of any significant head injury/trauma.

Primary outcomes:
measure: CogState Early Phase Battery, Groton Maze Learning Test (GMLT) as measured by the number of errors on the GMLT over time (area under the GMLT-time curve) over hours 1-12.
timeFrame: 1, 2, 3, 4, 6, 8, and 12 hours relative to administration of SQ scopolamine or SQ placebo
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Cho W, Maruff P, Connell J, Gargano C, Calder N, Doran S, Fox-Bosetti S, Hassan A, Renger J, Herman G, Lines C, Verma A. Additive effects of a cholinesterase inhibitor and a histamine inverse agonist on scopolamine deficits in humans. Psychopharmacology (Berl). 2011 Dec;218(3):513-24. doi: 10.1007/s00213-011-2344-y. Epub 2011 Jun 7.