Dimebon (PF-01913539)-Digoxin Drug-Drug Interaction Study In Healthy Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study To Evaluate The Steady-State Effect Of Dimebon (PF-01913539) On The Safety, Tolerability, And Steady-State Pharmacokinetics Of Digoxin In Healthy Subjects

This study has been designed to confirm, in healthy subjects, the lack of a clinically important pharmacokinetic interaction between Dimebon, at the proposed maximum commercial dose of 20 mg TID (administered every 8 hours), and digoxin (Lanoxin®) 0.125 mg QD, a sensitive P-gp substrate recommended by FDA.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease; Huntington Disease
• Intervention / Treatment: Drug: digoxin; Drug: digoxin; Drug: dimebon

• Study Type: Interventional
• Enrollment (Actual): 12
• 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female 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).
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

• A known history of hypersensitivity or previous intolerance to Dimebon or digoxin.
• Evidence or history of clinically significant hematological, renal, endocrine,pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic,seasonal allergies at time of dosing) disease or clinical findings at screening.
• Pregnant or nursing women; women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception as outlined in the protocol from at least 14 days prior to the first dose of study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; digoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days.	Drug: digoxin; digoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days.; Drug: digoxin; digoxin once daily (0.125 mg QD) for 14 days.
Experimental: B; digoxin once daily (0.125 mg QD) plus Dimebon three times a day, 8 hours apart for 14 days (10 mg TID on Days 1-7 and 20 mg TID on Days 8-14).	Drug: digoxin; digoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days.; Drug: digoxin; digoxin once daily (0.125 mg QD) for 14 days.; Drug: dimebon; Dimebon three times a day, 8 hours apart for 14 days (10 mg TID on Days 1-7 and 20 mg TID on Days 8-14).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC24 and Cmin of digoxin on Day 14	Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax, Tmax, Ae, and renal clearance of digoxin on Day 14	Day 14
Adverse event monitoring through Day 14 including physical/neurological examination findings	Day 14
Clinical safety assessments through Day 14 including chemistry, hematology, and vital signs	Day 14
12-lead ECGs through Day 14	Day 14

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: January 27, 2009
• First Submitted That Met QC Criteria: January 27, 2009
• First Posted (Estimate): January 29, 2009

Study Record Updates

• Last Update Posted (Estimate): June 12, 2009
• Last Update Submitted That Met QC Criteria: June 9, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: digoxin dimebon drug-drug interaction study
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Digoxin
• Other Study ID Numbers: B1451021