A Pharmacokinetic and Pharmacodynamic Study of Once-Daily and Twice-Daily Dosing With Canagliflozin in Healthy Adult Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of canagliflozin on glucose levels in the blood and urine when taken at 2 dose levels as a once-daily or twice-daily dosing regimen in healthy adult volunteers

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) in healthy adult volunteers. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with type 2 diabetes mellitus (T2DM). Patients in Cohort 1 will be randomized to receive Treatment A (one 300-mg tablet orally, by mouth [PO] once daily for 5 days) followed 10 days later by Treatment B (one 50-mg and one 100-mg tablet PO twice daily for 5 days) or Treatment B followed by Treatment A. Patients in Cohort 2 will be randomized to receive Treatment C (one 100-mg tablet PO once daily for 5 days) followed 10 days later by Treatment D (one 50-mg tablet PO twice daily for 5 days) or Treatment D followed by Treatment C.

Official Title
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An Open-Label, Multiple-Dose Study to Assess the Steady-State Pharmacokinetics, Pharmacodynamics and Safety of Once-Daily Versus Twice-Daily Dosing With Canagliflozin in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Canagliflozin 300 mg once daily and 150 mg twice daily
* Drug: Canagliflozin 100 mg once daily and 50 mg twice daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers with a body mass index (BMI, a measure of a person's weight in relation to height) between 18 and 30 kg/m2, inclusive, and a body weight of not less than 50 kg Exclusion Criteria: History of or current clinically significant medical illness as determined by the Investigator History of clinically significant allergies, especially known hypersensitivity or intolerance to lactose Known allergy to canagliflozin or any of the excipients of the formulation of canagliflozin

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 |
| --- | --- |
| Experimental: 001<br>Canagliflozin 300 mg once daily and 150 mg twice daily Treatment A (one 300-mg tablet once daily for 5 days) followed 10 days later by Treatment B (one 50-mg and one 100-mg tablet twice daily for 5 days) or Treatment B followed by Treatment A. | Drug: Canagliflozin 300 mg once daily and 150 mg twice daily<br>* Treatment A (one 300-mg tablet once daily for 5 days) followed 10 days later by Treatment B (one 50-mg and one 100-mg tablet twice daily for 5 days) or Treatment B followed by Treatment A.<br>|
| Experimental: 002<br>Canagliflozin 100 mg once daily and 50 mg twice daily Treatment C (one 100-mg tablet once daily for 5 days) followed 10 days later by Treatment D (one 50-mg tablet twice daily for 5 days) or Treatment D followed by Treatment C. | Drug: Canagliflozin 100 mg once daily and 50 mg twice daily<br>* Treatment C (one 100-mg tablet once daily for 5 days) followed 10 days later by Treatment D (one 50-mg tablet twice daily for 5 days) or Treatment D followed by Treatment C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of canagliflozin |  | Up to Day 5 after the last treatment | 
| Plasma concentrations of glucose |  | Up to Day 5 after the last treatment | 
| Urinary glucose excretion (UGE) |  | Up to Day 5 after the last treatment | 
| Renal threshold of glucose (RTG) |  | Up to Day 5 after the last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and type of adverse events reported |  | Up to 10 days after last dose (last dose is given on Day 8) | 
| Changes in hematology laboratory parameters |  | Up to 10 days after last dose (last dose is given on Day 8) | 
| Changes in chemistry laboratory parameters |  | Up to 10 days after last dose (last dose is given on Day 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin, Pharmacokinetics, Pharmacodynamics