A Phase 1, Randomized, Open-Label, Two-Way Crossover Study To Evaluate The Steady-State Effect Of Dimebon (PF 01913539) On The Single-Dose Pharmacokinetics And Pharmacodynamics Of Warfarin In Healthy Subjects

This study will evaluate the potential drug-drug interaction of Dimebon with the FDA-recommended CYP2C9 substrate warfarin in healthy subjects. Conformance with the guidance includes general study design using a randomized, open label, single-dose warfarin, steady-state Dimebon, 2-sequence, 2-treatment, 2-period crossover design with a minimum 7-day washout period between treatments.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 14
• 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 and/or female (non-childbearing potential) subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
• Prothrombin time (PT)/INR, and partial thromboplastin time (PTT).
• Plasma Protein C and Protein S activity (functional) within the normal reference range.

Exclusion Criteria:

• A known sensitivity or previous intolerance to Dimebon or warfarin.
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at Screening.
• Subjects receiving warfarin for treatment of active thromboembolic events (ie, pulmonary embolism, deep vein thrombosis), as well as subjects anticoagulated with prosthetic heart valves.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: A; A: Warfarin alone	Drug: Warfarin; A: a single oral dose of warfarin 25 mg administered on Day 1 of the relevant dosing period, as tablets.; Drug: Warfarin; B is oral doses of Dimebon 10 mg TID on Days 1 7 and Dimebon 20 mg TID on Days 8 17, with co administration of a single oral dose of warfarin 25 mg on Day 12 of the relevant dosing period, both as tablets
OTHER: B; B: Dimebon and Warfarin co-administration	Drug: Warfarin; A: a single oral dose of warfarin 25 mg administered on Day 1 of the relevant dosing period, as tablets.; Drug: Warfarin; B is oral doses of Dimebon 10 mg TID on Days 1 7 and Dimebon 20 mg TID on Days 8 17, with co administration of a single oral dose of warfarin 25 mg on Day 12 of the relevant dosing period, both as tablets; Drug: Dimebon; B is oral doses of Dimebon 10 mg TID on Days 1 7 and Dimebon 20 mg TID on Days 8 17, with co administration of a single oral dose of warfarin 25 mg on Day 12 of the relevant dosing period, both as tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Single dose pharmacokinetics (Cmax, AUCinf) of warfarin 25 mg with and without co-administration of steady-state Dimebon 20 mg TID in healthy adult subjects.	7+18 days
Single dose pharmacodynamics (INRmax, AUC-INR) of warfarin 25 mg with and without co-administration of steady-state Dimebon 20 mg TID in healthy adult subjects.	7+18 days
Safety and tolerability ( adverse event monitoring, physical examinations, vital signs, ECG's and clinical laboratory tests) of multiple doses of Dimebon 20 mg TID with a single dose of warfarin 25 mg in healthy adult subjects.	7+18 days

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

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: February 1, 2009
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): April 1, 2009

Study Registration Dates

• First Submitted: January 20, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (ESTIMATE): January 22, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Dimebon Warfarin Drug-Drug Interaction
• 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; Anticoagulants; Warfarin
• Other Study ID Numbers: B1451020