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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Alzheimer Disease, Huntington Disease

Intervention / Treatment
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* Drug: digoxin
* Drug: digoxin
* Drug: dimebon


Participation Criteria
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Eligibility Criteria
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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.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>digoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days. | Drug: digoxin<br>* digoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days.<br>|
| Experimental: B<br>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<br>* digoxin once daily (0.125 mg QD) for 14 days.<br>Drug: dimebon<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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digoxin dimebon drug-drug interaction study