Bioequivalence Study of Metformin Component of Fixed Dose Combination (FDC) Immediate Release (IR) Tablet of Canagliflozin and Metformin Compared to Metformin IR Tablet Co-administered With Canagliflozin in Healthy Fed and Fasted Participants

A Single-Dose, Open-Label, Randomized, 4-Way Crossover Pivotal Study to Assess the Bioequivalence of the Metformin Component of the Fixed Dose Combination Tablet of Canagliflozin and Metformin Immediate Release (IR) 1 x (150 mg/500 mg) With Respect to the Metformin IR Tablet (Locally Sourced From Canada [Glucophage, 1 x 500 mg]) Coadministered With Canagliflozin (1 x 50 mg and 1 x 100 mg) in Healthy Fed and Fasted Subjects

The purpose of this study is to evaluate the bioequivalence of metformin component of the canagliflozin and metformin immediate release (IR) fixed dose combination (FDC) tablet compared with the metformin IR tablet co-administered with canagliflozin in healthy fed and fasted participants.

Study Overview

• Status: Completed
• Conditions: Bioequivalence
• Intervention / Treatment: Drug: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]; Drug: Canagliflozin; Drug: Metformin

Detailed Description

This is a randomized (study medication assigned to participants by chance), open-label (identity of study drug will be known to volunteer and study staff), single-center, single-dose, 4-treatment, 4-way crossover (method used to switch participants from one study group to another in a clinical trial, like the flip of a coin) study in healthy adult participants. The study will have 3 phases: Screening Phase (approximately 3 weeks, Day -22 to Day -2), Open-Label Treatment Phase (consisting of 4 single-dose treatment periods of 3 days each [Day -1 to Day 2], each separated by a washout period of 7 days) and Follow-up Phase (5 to 7 days after last study-related procedure on Day 2 of treatment period 4). All the eligible participants will be randomly assigned to 1 of 4 treatment sequences and will receive 2 treatments under fasting and 2 treatments under fed conditions. Blood samples will be collected for evaluation of pharmacokinetics (how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time) at pre-dose and post-dose of study treatment. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States

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:

• Body mass index (BMI) between 18.5 and 30 kilogram per square meter (kg/m^2) (inclusive) and a body weight of not less than 50 kg

Exclusion Criteria:

• History of or current medical illness, abnormal values for hematology or clinical chemistry laboratory tests, or abnormal physical examination, vital signs or 12-lead electrocardiogram (ECG) deemed to be clinically significant by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence ABDC; Treatment A (1 immediate release (IR) fixed dose combination [FDC] tablet containing canagliflozin 150 milligram [mg] and metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.	Drug: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]; Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA/MET IR FDC; Drug: Canagliflozin; Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA; Drug: Metformin; Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: MET
Experimental: Treatment Sequence BCAD; Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.	Drug: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]; Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA/MET IR FDC; Drug: Canagliflozin; Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA; Drug: Metformin; Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: MET
Experimental: Treatment Sequence CDBA; Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.	Drug: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]; Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA/MET IR FDC; Drug: Canagliflozin; Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA; Drug: Metformin; Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: MET
Experimental: Treatment Sequence DACB; Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.	Drug: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]; Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA/MET IR FDC; Drug: Canagliflozin; Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: CANA; Drug: Metformin; Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.; Other Names: MET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Metformin	Plasma concentrations of metformin are used to evaluate how much metformin is in the blood over time.	Pre-dose, up to 24 hours afterdose
Plasma Concentration of Canagliflozin	Plasma concentrations of canagliflozin are used to evaluate how much canagliflozin is in the blood, 2 hours after dosing.	2 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number and type of adverse events will be reported from Day 1 of treatment period 1 through 5-7 days after treatment period 4 including a 7+/- 1 day washout period between treatment periods (total time is approximately 58 days).	Up to approximately 58 days
Clinical Laboratory Test	Clinically relevant changes occurring in laboratory safety parameters will be evaluated.	Up to approximately 58 days
Vital Signs	Blood pressure, pulse, and oral body temperature will be evaluated.	Up to approximately 58 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 18, 2014
• First Submitted That Met QC Criteria: August 18, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): November 25, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Healthy; Metformin; Bioequivalence; Canagliflozin
• 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: CR104980; 28431754DIA1071 (Other Identifier: Janssen Research & Development, LLC)