A Study Evaluating The Absorption Of Dimebon Into The Body From A Dimebon Solution Applied To The Skin

A Phase 1, Fixed Sequence, Cross-Over Study To Investigate The Single Dose Pharmacokinetics Of A Dimebon (Latrepirdine) Transdermal Solution Relative To The Immediate Release Formulation In Older Adults

To estimate the absorption, safety, and tolerability of a dimebon transdermal solution relative to the dimebon immediate release oral formulation.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease; Huntington's Disease
• Intervention / Treatment: Drug: Dimebon IR; Drug: Dimebon Transdermal; Drug: Dimebon Transdermal; Drug: Dimebon Transdermal

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Caucasian, male or females, 50 to 85 years inclusive.
• Subjects must have adequate space available on each side of the upper or middle back that is free from excessive hair, broken or irritated skin, tattoos, scars, moles, acne, and sunburn.

Exclusion Criteria:

• Evidence or history of any major medical or psychiatric illness or unstable medical condition within six months of Screening that may increase the risk associated with study participation.
• Subjects with any central nervous system disease including Alzheimer's disease, Parkinson's disease, Huntington disease, or any form of dementia.
• Subjects with any history of stroke, known cerebrovascular disease or subjects with any history of structural brain disease.
• Any history of epilepsy, seizure disorder (i.e., including febrile seizures) or convulsion.
• Subjects with any skin disorders that might prevent application of the dimebon solution including, but not limited to, any known sensitivity to adhesives.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1	Drug: Dimebon IR; A single, oral 10 mg dose of dimebon dihydrochloride (equivalent to 8.2 mg free base) immediate release will be administered.; Drug: Dimebon Transdermal; A single, transdermal 5 mg dose of dimebon free base solution will be applied to the back over a 24 hour period. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.; Drug: Dimebon Transdermal; A single, to be determined dose of dimebon free base solution will be applied to the back over a 24 hour period. The dose level chosen will be determined based on the pharmacokinetic/safety profile of the 5 mg dose. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.; Drug: Dimebon Transdermal; A single, to be determined dose of dimebon free base solution will be applied to the back over a 24 hour period. The dose level chosen will be determined based on the pharmacokinetic/safety profile of the 5 mg dose in Cohort 1. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.
Other: Cohort 2	Drug: Dimebon IR; A single, oral 10 mg dose of dimebon dihydrochloride (equivalent to 8.2 mg free base) immediate release will be administered.; Drug: Dimebon Transdermal; A single, transdermal 5 mg dose of dimebon free base solution will be applied to the back over a 24 hour period. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.; Drug: Dimebon Transdermal; A single, to be determined dose of dimebon free base solution will be applied to the back over a 24 hour period. The dose level chosen will be determined based on the pharmacokinetic/safety profile of the 5 mg dose. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.; Drug: Dimebon Transdermal; A single, to be determined dose of dimebon free base solution will be applied to the back over a 24 hour period. The dose level chosen will be determined based on the pharmacokinetic/safety profile of the 5 mg dose in Cohort 1. A double-blinded vehicle (placebo) solution will be applied concurrently to a contralateral body site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic endpoints include dimebon area under the curve from 0 to the last quantifiable concentration (AUClast) and dimebon area under the curve from 0 to infinity (AUCinf) as permitted by data	4 to 6 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety endpoints include subjective symptoms/objective findings (including skin irritation), clinical safety laboratory assessments, 12 lead ECGs, and supine vital signs.	4 to 6 days

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

Publications and helpful links

General Publications

• Chew ML, Mordenti J, Yeoh T, Ranade G, Qiu R, Fang J, Liang Y, Corrigan B. Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example. Pharm Res. 2016 Aug;33(8):1873-80. doi: 10.1007/s11095-016-1922-4. Epub 2016 Apr 12.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: October 6, 2009
• First Submitted That Met QC Criteria: October 6, 2009
• First Posted (Estimate): October 7, 2009

Study Record Updates

• Last Update Posted (Estimate): February 3, 2010
• Last Update Submitted That Met QC Criteria: February 2, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: percutaneous transcutaneous dimebon transdermal pharmacokinetics
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Tauopathies; Cognition Disorders; Chorea; Alzheimer Disease; Huntington Disease
• Other Study ID Numbers: B1451038