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

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

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).

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Cohort A; 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; 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; Drug: Scopolamine + Donepezil 5 mg + PF-04995274 Placebo; 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; Drug: Scopolamine + Donepezil 10mg + PF-04995274 Placebo; 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; Drug: Scopolamine + Donepezil Placebo + PF-04995274 0.25 mg; 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; Drug: Scopolamine + Donepezil Placebo + PF-04995274 15 mg; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: April 28, 2011
• First Submitted That Met QC Criteria: April 28, 2011
• First Posted (ESTIMATE): May 2, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 17, 2011
• Last Update Submitted That Met QC Criteria: November 16, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: attention cognition memory problem solving scopolamine challenge
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Antiemetics; Gastrointestinal Agents; Adjuvants, Anesthesia; Nootropic Agents; Cholinesterase Inhibitors; Mydriatics; Donepezil; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: B1661006