A Pharmacokinetic and Pharmacodynamic Study of Metformin and Canagliflozin in Healthy Adult Volunteers

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

The purpose of the study is to investigate the potential interaction between multiple oral doses of canagliflozin and a single oral dose of metformin in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Canagliflozin/Metformin

Detailed Description

This is an open-label (volunteers will know the names of treatments they are assigned) single-center study of canagliflozin and metformin 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) and metformin is an approved treatment for patients with T2DM. Canagliflozin will be administered orally (by mouth) as a single 300-mg tablet on Days 4, 5, 6, 7, and 8 and metformin will be administered orally as two 1,000 mg tablets on Days 1 and 8. Both canagliflozin and metformin tablets will be taken with 8 ounces (240 mL) of water.

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

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:

• 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.

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 metformin or any of the excipients of the formulation of canagliflozin or metformin
• Known allergy to heparin or history of heparin induced thrombocytopenia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; Canagliflozin/Metformin Two 1000-mg tablets of metformin on Day 1 followed by one 300-mg tablet of canagliflozin once daily on Days 4 through 8 followed by two 1000-mg tablets of metformin and one 300-mg tablet of canagliflozin on Day 8.	Drug: Canagliflozin/Metformin; Two 1000-mg tablets of metformin on Day 1 followed by one 300-mg tablet of canagliflozin once daily on Days 4 through 8, followed by two 1000-mg tablets of metformin and one 300-mg tablet of canagliflozin on Day 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of canagliflozin	At protocol-specified times up to Day 11
Plasma concentrations of metformin	At protocol-specified times up to Day 11)
Urine concentrations of metformin	At protocol-specified times up to Day 10)
Plasma concentrations of glucose	Up to Day 9
Urinary glucose excretion (UGE)	Up to Day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
The number and type of adverse events reported	Up to Day 8

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Devineni D, Manitpisitkul P, Murphy J, Skee D, Wajs E, Mamidi RN, Tian H, Vandebosch A, Wang SS, Verhaeghe T, Stieltjes H, Usiskin K. Effect of canagliflozin on the pharmacokinetics of glyburide, metformin, and simvastatin in healthy participants. Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):226-36. doi: 10.1002/cpdd.166. Epub 2014 Oct 27.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion: December 7, 2022
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: December 23, 2010
• First Submitted That Met QC Criteria: January 7, 2011
• First Posted (Estimate): January 10, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2013
• Last Update Submitted That Met QC Criteria: July 26, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Canagliflozin; Metformin (GLUCOPHAGE IR)
• 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: CR017815; 28431754DIA1028

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No