Assessment Of The Effects Of Single Doses Of An Investigational Drug, Given Alone Or With Donepezil, On Scopolamine-Induced Changes In Memory And Learning In Healthy Adults

Study Overview
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Brief Summary
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This study is designed to look at the potential for an investigational drug (PF-04995274, under development by Pfizer, Inc. as a potential treatment for Alzheimer's disease) to reverse changes in memory and learning/problem solving skills caused by co-administration of a marketed drug called scopolamine. Scopolamine is known to cause temporary changes in memory and learning/problem solving skills that are similar to those seen in people with alzheimer's disease(AD).

Detailed Description
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Changes in sponsor's organizational strategy have led to the decision to terminate the study and therefore to not conduct the second cohort (Cohort B/arms 2 and 3) . This decision was not based on significant safety concerns. Date of termination (ie, the date the site was notified to stop study activities) was 12 Oct 2011.

Official Title
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A Randomized, Double-Blind, Sponsor Unblinded, Placebo- And Positive- Controlled Study To Evaluate The Effects Of Single Oral Administrations Of PF-04995274, Alone Or In Combination With Donepezil, On Scopolamine-Induced Deficits In Psychomotor And Cognitive Function In Healthy Adults

Conditions
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Healthy

Intervention / Treatment
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* Drug: Scopolamine + Donepezil Placebo + PF-04995274 Placebo
* Drug: Scopolamine + Donepezil 5 mg + PF-04995274 Placebo
* Drug: Scopolamine + Donepezil 10mg + PF-04995274 Placebo
* Drug: Scopolamine + Donepezil Placebo + PF-04995274 0.25 mg
* Drug: Scopolamine + Donepezil Placebo + PF-04995274 15 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female volunteers; females must be of non-childbearing potential. Weight with normal limits for height. Willing to comply with study schedule and able to complete 2 practice sessions (pre-study) with computerized memory and learning/problem solving tests. Exclusion Criteria: Positive urine drug screen; concurrent use of prescription or over-the-counter (OTC) drugs or dietary supplements within 7 days or 5 half-lives prior to the first dose of study medication. Use of medications with significant serotonergic, cholinergic or anticholinergic side effects [SSRIs, pyridostigmine, tricyclic antidepressants, meclizine, oxybutynin]) within 4 weeks of first dose of study drug. Glaucoma Abnormal electrocardiogram (ECG) Treatment with an investigational drug within 30 days of dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort A<br>Parallel design with 5 unique treatment groups Donepezil tablets and matching placebo tablets may be overencapsulated as needed. | Drug: Scopolamine + Donepezil Placebo + PF-04995274 Placebo<br>* Scopolamine 0.5 mg subcutaneously x 1 dose on Day 1 Donepezil-matching placebo tablet x 1 dose on Day 1 PF-04995274 matching placebo oral liquid x 1 dose on Day 1<br>Drug: Scopolamine + Donepezil 5 mg + PF-04995274 Placebo<br>* Scopolamine 0.5 mg subcutaneously x 1 dose on Day 1 Donepezil 5 mg tablet orally x 1 dose on Day 1 PF-04995274 matching placebo oral liquid x 1 dose on Day 1<br>Drug: Scopolamine + Donepezil 10mg + PF-04995274 Placebo<br>* Scopolamine 0.5 mg subcutaneously x 1 dose on Day 1 Donepezil 10 mg (2 x 5 mg tablets) orally x 1 dose on Day 1 PF-04995274 matching placebo oral liquid x 1 dose on Day 1<br>Drug: Scopolamine + Donepezil Placebo + PF-04995274 0.25 mg<br>* Scopolamine 0.5 mg subcutaneously x 1 dose on Day 1 Donepezil-matching placebo tablet x 1 dose on Day 1 PF-04995274 0.25 mg oral liquid x 1 dose on Day 1<br>Drug: Scopolamine + Donepezil Placebo + PF-04995274 15 mg<br>* Scopolamine 0.5 mg subcutaneously x 1 dose on Day 1 Donepezil-matching placebo tablet x 1 dose on Day 1 PF-04995274 15 mg oral liquid x 1 dose on day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Groton Maze Learning Test (Total Errors) |  | Day 1 of each period at 8 time points from 0-12 hr postdose relative to scopolamine dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection Task (Speed; included in CogState test battery) |  | Day 1 of each period at 8 time points from 0-12 hrs postdose relative to scopolamine dosing | 
| Identification Task (Speed; included in CogState test battery) |  | Day of each period at 8 time points from 0-12 hrs postdose relative to scopolamine dosing | 
| One Card Learning Task (Accuracy of Performance; included in CogState test battery) |  | Day 1 of each period at 8 time points from 1-12 hrs postdose relative to scopolamine dosing | 
| Bond-Lader Visual Analogue Scales |  | Day 1 of each period at 8 time points from 1-12 hours postdose relative to scopolamine dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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attention cognition memory problem solving scopolamine challenge