A Study to Investigate Whether Pharmacokinetic and Pharmacodynamic Interactions Exist Between Metformin and Canagliflozin (JNJ-28431754) in Healthy Volunteers

An Open-Label, Fixed Sequence, Single and Multiple Dose Study in Male and Female Subjects to Investigate the Potential for Pharmacokinetic and Pharmacodynamic Interaction Between Metformin and JNJ-28431754

The purpose of this study is to investigate whether there is a drug-drug interaction between multiple doses of canagliflozin (JNJ-28431754) and a single dose of metformin. The safety and tolerability of canagliflozin will also be assessed.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Metformin; Drug: Canagliflozin (JNJ-28431754)

Detailed Description

This study is an open-label (all volunteers and study staff know the identity of the assigned treatment), fixed sequence (all volunteers receive the same medication on the same days), single and multiple-dose study to determine how metformin (a blood glucose-lowering agent used to treat patients with diabetes) affects the pharmacokinetics (ie, how the body affects the drug) and the pharmacodynamics (ie, how the drug affects the body) of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus). The effect of canagliflozin on the pharmacokinetics and pharmacodynamics of metformin will also be evaluated. The study will consist of 3 phases: a screening phase, an open-label treatment phase, and an end-of-study (or follow-up) phase. Each volunteer will participate in the study for approximately 39 days.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Neptune, New Jersey, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Volunteers must have a Body Mass Index (BMI [weight (kg) / height (m)2]) between 18.5 and 35 kg/m2, inclusive
• Volunteers must be non-smokers or non-tobacco users

Exclusion Criteria:

- History of or currently active illness that the Investigator considers to be clinically significant and should exclude the volunteer from the study or that could interfere with the interpretation of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin + canagliflozin (JNJ-28431754); Each volunteer will receive a single dose of metformin on Day 1 followed by canagliflozin (JNJ-28431754) once daily on Days 4 to 7. On Day 8, volunteers will receive a single dose of canagliflozin in combination with a single dose of metformin.	Drug: Metformin; One 1,000 mg tablet of metformin taken orally (by mouth) on Day 1 and Day 8.; Drug: Canagliflozin (JNJ-28431754); Four 25 mg tablets of canagliflozin (JNJ-28431754) taken orally on Days 4 through 8.; Other Names: JNJ-28431754

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum plasma concentration (Cmax) of canagliflozin (JNJ-28431754)	Cmax (a measure of the body's exposure to canagliflozin [JNJ-28431754]) will be compared before and after administration of a single dose of metformin.	Up to Day 8
The area under the plasma concentration-time curve (AUC) for canagliflozin (JNJ-28431754)	AUC (a measure of the body's exposure to canagliflozin [JNJ-28431754]) will be compared before and after administration of a single dose of metformin.	Up to Day 8
The maximum plasma concentration (Cmax) of metformin	Cmax (a measure of the body's exposure to metformin will be compared before and after administration of multiple doses of canagliflozin (JNJ-28431754).	Up to Day 8
The area under the plasma concentration-time curve (AUC) for metformin	AUC (a measure of the body's exposure to metformin will be compared before and after administration of multiple doses of canagliflozin (JNJ-28431754).	Up to Day 8
24-hour urine glucose excretion	24-hour urine glucose excretion will be compared following a single dose of metformin, multiple doses of canagliflozin (JNJ-28431754), or multiple doses of canagliflozin in combination with a single dose of metformin.	Up to Day 10
24-hour area under the serum glucose concentration-time curve	24-hour area under the serum glucose concentration-time curve will be compared following a single dose of metformin, multiple doses of canagliflozin (JNJ-28431754), or multiple doses of canagliflozin in combination with a single dose of metformin.	Up to Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of volunteers with adverse events as a measure of safety and tolerability	up to 18 days

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

Helpful Links

• An Open-Label Study to Investigate the Absorption, Metabolism, and Excretion of JNJ-28431754 in Healthy Male Subjects Following a Single Oral Dose Administration of 14C-JNJ-28431754

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: December 20, 2012
• First Posted (Estimate): December 25, 2012

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Metformin; Pharmacodynamics; Canagliflozin (JNJ-28431754)
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Canagliflozin
• Other Study ID Numbers: CR013636; 28431754NAP1004 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)