A Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin (JNJ-28431754) in Volunteers With Varying Degrees of Kidney Function

Phase 1

Completed

• Conditions: Renal Insufficiency; Healthy
• Interventions: Drug: Canagliflozin (JNJ-28431754)

• Registration Number: NCT01759576
• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary

The purpose of this study is to assess the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of canagliflozin (JNJ-28431754) after administration of a single dose to non-diabetic volunteers with normal kidney function and non-diabetic volunteers with varying degrees of kidney impairment (including volunteers with end-stage renal disease requiring hemodialysis).

Detailed Description

This study will be an open label (all volunteers and study staff know the identity of the assigned treatment), single-dose, multicenter (the study will be conducted at more than one center), parallel-group study (each group of volunteers will be treated at the same time) to assess the pharmacokinetics and pharmacodynamics of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) in volunteers with varying degrees of kidney function. The study will consist of 3 phases: a screening phase, an open-label treatment phase, and an end-of study (or follow-up) phase. Volunteers will be assigned to 1 of 5 groups (depending on kidney function): group 1 will have normal kidney function; group 2 will have mild kidney impairment; group 3 will have moderate kidney impairment; group 4 will have severe kidney impairment; and group 5 will comprise volunteers requiring hemodialysis. Volunteers in groups 1 through 4 will receive a single dose of canagliflozin on Day 1. Volunteers in group 5 will receive a single dose of canagliflozin following dialysis and then, approximately 10 days later, they will receive a second dose before dialysis. Volunteers in groups 1 through 4 will participate in the study for 27 days. Volunteers in group 5 will participate in the study for 40 days.

Study Timeline

• Study Start: 2008-03
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Study First Submitted: 2012-12-24
• Study First Submitted QC: 2012-12-28
• Study First Posted: 2013-01-03
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-27
• Last Update Posted: 2013-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 20 and 40 kg/m2 (inclusive), and body weight not less than 50 kg
• Volunteers must smoke no more than 10 cigarettes, or 2 cigars, or 2 pipes of tobacco per day for at least 6 months before first study drug administration

Exclusion Criteria

• History of or currently 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
• Volunteers with end stage renal disease receiving dialysis treatment other than intermittent hemodialysis
• Volunteers with end stage renal disease who have received a renal transplantation within 1 year before screening
• Volunteers with end stage renal disease diagnosed with renal carcinoma within 1 year before screening
• Volunteers with end stage renal disease receiving immunosuppressive medications, including steroids

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 3 (moderate kidney impairment)	Canagliflozin (JNJ-28431754)	Each volunteer will receive a single dose of canagliflozin (JNJ-28431754) on Day 1
Group 4 (severe kidney impairment)	Canagliflozin (JNJ-28431754)	Each volunteer will receive a single dose of canagliflozin (JNJ-28431754) on Day 1
Group 1 (normal kidney function)	Canagliflozin (JNJ-28431754)	Each volunteer will receive a single dose of canagliflozin (JNJ-28431754) on Day 1
Group 2 (mild kidney impairment)	Canagliflozin (JNJ-28431754)	Each volunteer will receive a single dose of canagliflozin (JNJ-28431754) on Day 1
Group 5 (hemodialysis)	Canagliflozin (JNJ-28431754)	Each volunteer will receive a single dose of canagliflozin (JNJ-28431754) on Day 1 following completion of hemodialysis. Approximately 10 days later, each volunteer will receive another single dose of canagliflozin before hemodialysis begins.

Primary Outcome Measures

Name	Time	Method
Plasma concentrations of canagliflozin (JNJ-28431754) in varying degrees of kidney function	Up to Day 6	Plasma concentrations of canagliflozin (JNJ-28431754) following the administration of a single dose of canagliflozin will be used to determine pharmacokinetic parameters for canagliflozin (measurements describing how the body affects the drug) in varying degrees of kidney function.
Change from baseline in 24-hour urine glucose excretion in varying degrees of kidney function	Day -1 (Baseline) to Day 3	Change from baseline in 24-hour urine glucose excretion following the administration of a single dose of canagliflozin (JNJ-28431754) will be used to evaluate the pharmacodynamics of canagliflozin (ie, how the drug affects the body) in varying degrees of kidney function.
Plasma concentrations of canagliflozin (JNJ-28431754) metabolites in varying degrees of kidney function	Up to Day 6	Plasma concentrations of canagliflozin (JNJ-28431754) metabolites following the administration of a single dose of canagliflozin will be used to determine pharmacokinetic parameters for canagliflozin metabolites (measurements describing how the body affects the metabolites) in varying degrees of kidney function.