A Study to Assess the Effects of Canagliflozin (JNJ-28431754) on the Pharmacokinetics and Safety of Digoxin in Healthy Volunteers.

Study Overview
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Brief Summary
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The purpose of this study is to determine how multiple doses of canagliflozin (JNJ-28431754) affect the pharmacokinetics (ie, how the body affects the drug) of multiple doses of digoxin. The safety and tolerability of canagliflozin will also be assessed in healthy volunteers.

Detailed Description
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This study will be an open label (all volunteers and study staff know the identity of the assigned treatment), randomized (the treatment is assigned by chance), multiple dose, cross-over study (all volunteers will switch from one treatment to another) to determine how canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) affects the pharmacokinetics of digoxin (a drug used to treat various heart conditions). Volunteers will be randomly assigned to 1 of 2 treatment sequence groups: Group AB or Group BA. Volunteers assigned to Group AB will be given Treatment A: digoxin once a day for 7 days. Volunteers assigned to Group BA will be given Treatment B: digoxin and canagliflozin once a day for 7 days. A washout period (when no medication is given) of at least 14 days will follow the first 7-day treatment period. Following the washout period, volunteers will be assigned to the treatment that they did not receive during the first treatment period. This second treatment period will last for 7 days. Each volunteer will participate in the study for approximately 60 days.

Official Title
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An Open-Label, 2-Period, Crossover Study to Evaluate the Effects of Multiple Doses of JNJ-28431754 on the Pharmacokinetics of Multiple Doses of Digoxin in Healthy Subjects.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Digoxin 0.5 mg
* Drug: Digoxin 0.25 mg
* Drug: Canagliflozin (JNJ-28431754)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg Exclusion Criteria: History of, or current active illness, considered to be clinically significant by the Investigator, or any other illness that the Investigator considers should exclude the patient from the study, or that could interfere with the interpretation of the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>Each volunteer will receive digoxin once daily on Days 1 through 7. | Drug: Digoxin 0.5 mg<br>* Two 0.25 mg tablets (0.5 mg total dose) taken orally (by mouth) on Day 1.<br>* Other names: Lanoxin;Drug: Digoxin 0.25 mg<br>* One 0.25 mg tablet taken orally on Days 2 through 7.<br>* Other names: Lanoxin;|
| Experimental: Treatment B<br>Each volunteer will receive digoxin once daily on Days 1 through 7 in combination with canagliflozin (JNJ-28431754) once daily on Days 1 through 7. | Drug: Digoxin 0.5 mg<br>* Two 0.25 mg tablets (0.5 mg total dose) taken orally (by mouth) on Day 1.<br>* Other names: Lanoxin;Drug: Digoxin 0.25 mg<br>* One 0.25 mg tablet taken orally on Days 2 through 7.<br>* Other names: Lanoxin;Drug: Canagliflozin (JNJ-28431754)<br>* One 300 mg tablet taken orally on Days 1 through 7.<br>* Other names: JNJ-28431754;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of digoxin | Comparison of plasma concentrations of digoxin following administration of digoxin alone (Treatment A) or in combination with canagliflozin (JNJ-28431754) (Treatment B). This will be used to determine whether there is a pharmacokinetic interaction between digoxin and canagliflozin. | Days 5 through 7 | 
| Urine concentration of digoxin | Comparison of the urine concentrations of digoxin following administration of digoxin alone (Treatment A) or in combination with canagliflozin (JNJ-28431754) (Treatment B). This will be used to determine whether there is a pharmacokinetic interaction between canagliflozin and digoxin. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| There are no secondary outcome measures |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Canagliflozin (JNJ-28431754), Pharmacokinetics, Digoxin (LANOXIN)