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

Phase 1

Completed

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

• Registration Number: NCT01756417
• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary

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.

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 Timeline

• Study Start: 2007-10
• Primary Completion: 2007-11
• Study Completion: 2007-11
• Study First Submitted: 2012-12-20
• Study First Submitted QC: 2012-12-20
• Study First Posted: 2012-12-25
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-28
• Last Update Posted: 2016-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin + canagliflozin (JNJ-28431754)	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.
Metformin + canagliflozin (JNJ-28431754)	Metformin	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.

Primary Outcome Measures

Name	Time	Method
The maximum plasma concentration (Cmax) of canagliflozin (JNJ-28431754)	Up to Day 8	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.
The maximum plasma concentration (Cmax) of metformin	Up to Day 8	Cmax (a measure of the body's exposure to metformin will be compared before and after administration of multiple doses of canagliflozin (JNJ-28431754).
The area under the plasma concentration-time curve (AUC) for canagliflozin (JNJ-28431754)	Up to Day 8	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.
The area under the plasma concentration-time curve (AUC) for metformin	Up to Day 8	AUC (a measure of the body's exposure to metformin will be compared before and after administration of multiple doses of canagliflozin (JNJ-28431754).
24-hour urine glucose excretion	Up to Day 10	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.
24-hour area under the serum glucose concentration-time curve	Up to Day 8	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.

Secondary Outcome Measures

Name	Time	Method
The number of volunteers with adverse events as a measure of safety and tolerability	up to 18 days