A Drug Interaction Study of Warfarin and Canagliflozin in Healthy Adult Volunteers

Study Overview
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Brief Summary
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The purpose of the study is to assess the effect of multiple oral doses of canagliflozin on a single oral dose of warfarin.

Detailed Description
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This is an open-label (volunteers will know the names of treatments they are assigned) single-center study of canagliflozin (JNJ-28431754) and warfarin in healthy adult volunteers. Canagliflozin is a drug currently under development to lower blood sugar levels in patients with type 2 diabetes mellitus and warfarin is an approved anticoagulant (ie, a drug that stops blood from clotting). After an overnight fast (without eating food) of at least 10 hours, volunteers will receive Sequence 1 (canagliflozin 300 mg, orally, once daily on Days 1-12 with a single, oral 30 mg dose of warfarin on Day 6 [Treatment A] followed 14 days later by a single, oral 30 mg dose of warfarin on Day 1 [Treatment B]) OR Sequence 2 (Treatment B followed 14 days later by Treatment A).

Official Title
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An Open-Label Drug Interaction Study to Assess the Pharmacokinetics and Pharmacodynamics of Warfarin When Administered Alone and in Combination With Multiple-Dose JNJ-28431754 (Canagliflozin) in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Canagliflozin/Warfarin
* Drug: Canagliflozin/Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers with a body mass index between 18 and 30 kg/m Exclusion Criteria: Any blood coagulation disorder determined to be clinically relevant by the Investigator Medications known to affect coagulation taken within 7 to 14 days of study entry

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Canagliflozin/Warfarin Treatment A: Tablets oral canagliflozin 300 mg once daily for 12 days and canagliflozin 300 mg + warfarin 30 mg single dose on Day 6 followed 14 days later by Treatment B: Tablets oral warfarin 30 mg single dose on Day 1 | Drug: Canagliflozin/Warfarin<br>* Treatment A: Tablets, oral, canagliflozin 300 mg, once daily for 12 days and canagliflozin 300 mg + warfarin 30 mg, single dose on Day 6 followed 14 days later by Treatment B: Tablets, oral, warfarin 30 mg, single dose on Day 1<br>|
| Experimental: 002<br>Canagliflozin/Warfarin Treatment B: Tablets oral warfarin 30 mg single dose on Day 1 followed 14 days later by Treatment A: Tablets oral canagliflozin 300 mg once daily for 12 days and canagliflozin 300 mg + warfarin 30 mg single dose on Day 6 | Drug: Canagliflozin/Warfarin<br>* Treatment B: Tablets, oral, warfarin 30 mg, single dose on Day 1 followed 14 days later by Treatment A: Tablets, oral, canagliflozin 300 mg, once daily for 12 days and canagliflozin 300 mg + warfarin 30 mg, single dose on Day 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of canagliflozin |  | At protocol-specified times during Treatment A on Days 1 through 12. | 
| Plasma concentrations of warfarin |  | At protocol specified times during Treatment A on Days 6 through 13 | 
| Plasma concentrations of warfarin |  | At protocol specified times during Treatment B on Days 1 through 8 | 
| Measurement of Prothrombin time (PT) to assess the international normalized ratio (INR) |  | At protocol-specified times during Treatment A on Days 6 through 13 | 
| Measurement of PT to assess the INR |  | At protocol-specified time points during Treatment B on Days 1 through 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and type of adverse events reported |  | Day 1 of Treatment A through 10 days after Day 8 of Treatment B | 
| The number and type of adverse events reported |  | Day 1 of Treatment B through 10 days after Day 13 of Treatment A | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin (JNJ-28431754), Warfarin, Pharmacokinetic, Pharmacodynamic, Prothrombin time (PT), International normalized ratio (INR)