A Study to Assess the Pharmacokinetics and Pharmacodynamics of Canagliflozin in Healthy Chinese Volunteers

A Double-Blind, Randomized, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Single-Dose Pharmacokinetics and Pharmacodynamics of JNJ-28431754 (Canagliflozin) in Healthy Chinese Subjects

The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication) and pharmacodynamics (the action of the medication on the body) of JNJ-28431754 (canagliflozin) and its main metabolites (break-down products) following 2 different doses of canagliflozin in healthy Chinese volunteers. Safety and tolerability of canagliflozin will also be assessed.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Treatment A: Canagliflozin 100 mg; Drug: Treatment B: Canagliflozin 300 mg; Other: Treatment C: Placebo

Detailed Description

This study will be a double-blind (neither the Investigator nor volunteer knows the assigned treatment), randomized (the treatment is assigned by chance), placebo-controlled (one of the study treatments is inactive), single-dose, 3-way cross over study (all volunteers will receive each of the 3 treatments but in a different order) in healthy Chinese volunteers. Volunteers will be assigned to 1 of 3 treatment sequence groups (ABC, BCA, or CAB). The treatment sequence will be decided by randomization. Treatment A will be a single oral (by mouth) dose of 100 mg of canagliflozin. Treatment B will be a single oral dose of 300 mg of canagliflozin. Treatment C will be a single oral dose of placebo (inactive medication). Each treatment will be given during a treatment period of 5 days duration; each treatment period will be separated by a washout period (a time period with no medication) of at least 10 days. Canagliflozin is currently being investigated for the treatment of type 2 diabetes mellitus (T2DM).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Volunteers must be non-smokers for at least 6 months before first study drug administration
• Volunteers must consume no more than 4 to 5 cups of coffee or tea or 8 cans of cola each day

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
• Female volunteer is breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence 1: Treatment A-B-C; The study consists of 3 single-dose treatment periods. Each treatment period will be 5 days in duration. Successive treatment periods will be separated by a washout period (with no medication) of 10 days.	Drug: Treatment A: Canagliflozin 100 mg; Volunteers will receive one 100 mg over-encapsulated tablet of canagliflozin as a single oral (by mouth) dose on Day 1.; Other Names: JNJ-28431754; Drug: Treatment B: Canagliflozin 300 mg; Volunteers will receive one 300 mg over-encapsulated tablet of canagliflozin as a single oral dose on Day 1.; Other Names: JNJ-28431754; Other: Treatment C: Placebo; Volunteers will receive one matching placebo (inactive medication) capsule as a single dose on Day 1.
EXPERIMENTAL: Sequence 2: Treatment B-C-A; The study consists of 3 single-dose treatment periods. Each treatment period will be 5 days in duration. Successive treatment periods will be separated by a washout period (with no medication) of 10 days.	Drug: Treatment A: Canagliflozin 100 mg; Volunteers will receive one 100 mg over-encapsulated tablet of canagliflozin as a single oral (by mouth) dose on Day 1.; Other Names: JNJ-28431754; Drug: Treatment B: Canagliflozin 300 mg; Volunteers will receive one 300 mg over-encapsulated tablet of canagliflozin as a single oral dose on Day 1.; Other Names: JNJ-28431754; Other: Treatment C: Placebo; Volunteers will receive one matching placebo (inactive medication) capsule as a single dose on Day 1.
EXPERIMENTAL: Sequence 3: Treatment C-A-B; The study consists of 3 single-dose treatment periods. Each treatment period will be 5 days in duration. Successive treatment periods will be separated by a washout period (with no medication) of 10 days.	Drug: Treatment A: Canagliflozin 100 mg; Volunteers will receive one 100 mg over-encapsulated tablet of canagliflozin as a single oral (by mouth) dose on Day 1.; Other Names: JNJ-28431754; Drug: Treatment B: Canagliflozin 300 mg; Volunteers will receive one 300 mg over-encapsulated tablet of canagliflozin as a single oral dose on Day 1.; Other Names: JNJ-28431754; Other: Treatment C: Placebo; Volunteers will receive one matching placebo (inactive medication) capsule as a single dose on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of canagliflozin and its major metabolites following a single 100 mg and 300 mg dose	Plasma concentrations of canagliflozin and its major metabolites will be used to determine pharmacokinetic parameters (measurements that explore what the body does to the drug) for canagliflozin and its major metabolites.	Up to Day 4
Urine concentrations of canagliflozin and its major metabolites following a single 100 mg and 300 mg dose	Urine concentrations of canagliflozin and its major metabolites will be used to determine pharmacokinetic parameters for canagliflozin and its major metabolites.	Up to Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal threshold for glucose excretion following a single 100 mg dose of canagliflozin, 300 mg dose of canagliflozin, and placebo (inactive medication)	Renal threshold is defined as the plasma glucose concentration above which glucose is excreted in the urine.	Up to Day 2
Urine glucose excretion (UGE) following a single 100 mg dose of canagliflozin, 300 mg dose of canagliflozin, and placebo (inactive medication)	UGE is equal to the amount of glucose excreted into the urine over defined time intervals.	Up to Day 2
Mean plasma glucose concentration following a single 100 mg dose of canagliflozin, 300 mg dose of canagliflozin, and placebo (inactive medication)		Up to Day 2

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Chen X, Hu P, Vaccaro N, Polidori D, Curtin CR, Stieltjes H, Sha S, Weiner S, Devineni D. Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Canagliflozin in Healthy Chinese Subjects. Clin Ther. 2015 Jul 1;37(7):1483-1492.e1. doi: 10.1016/j.clinthera.2015.04.015. Epub 2015 Jun 3.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: October 12, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (ESTIMATE): October 16, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 20, 2013
• Last Update Submitted That Met QC Criteria: February 18, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Pharmacodynamics; Canagliflozin; JNJ-28431754
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: CR100923; 28431754DIA1026 (OTHER: Janssen Research & Development, LLC)