A Bioequivalence Study of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) With Respect to the Individual Components

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the bioequivalence of the fixed dose combination (two components combined in one tablet) of canagliflozin and metformin extended release (XR) tablet (dose of 2 X 150 mg/1,000 mg) with respect to the individual components of canagliflozin (1 x 300 mg) and metformin XR tablet (4 x 500 mg) in healthy fed participants.

Detailed Description
-----------------
This is a randomized (the study medication is assigned by chance), open-label (physicians and participants know the identity of the assigned treatment), single-center, single-dose, 3-treatment, 3-way crossover (the same medications are provided to all participants but in different sequence) study of canagliflozin (CANA) and metformin extended release (MET XR) combined in one tablet, in comparison with tablets containing the individual components. Two Fixed Dose Combinations (FDCs) will be evaluated during the study (two types of tablets). The tablets will be of the same strength (150 mg CANA/1,000 mg MET XR) and will be compared with equal doses of the individual drugs: canagliflozin (1 x 300 mg tablet) and metformin XR (4 x 500 mg tablets). Thus, there will be 3 treatment periods in the study: Treatment A: Reference treatment of individual components administered concurrently; Treatment B: CANA/MET XR FDC, formulation 1; and Treatment C: CANA/MET XR FDC, formulation 2. Approximately 42 healthy adult participants will be randomly assigned to 1 of the 3 treatments groups, and then each group will receive all three treatments in different sequences (3-way crossover). The study will consist of 3 phases: a Screening Phase of approximately 3 weeks, an Open-Label Treatment Phase consisting of 3 single-dose Treatment Periods of 5 days each separated by a washout period of 10 to 14 days and a Follow-up Phase occurring 7 to 10 days after the last study-related procedure of Treatment Period 3. The total duration of the study will be about 70 days for each participant.

Official Title
-----------------
A Single-Dose, Open-Label, Randomized, 3-Way Crossover Pivotal Study to Assess the Bioequivalence of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) (2 x 150 mg/1,000 mg) With Respect to the Individual Components of Canagliflozin (1 x 300 mg) and Metformin XR Tablet (4 x 500 mg) in Healthy Fed Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Canagliflozin, 300 mg
* Drug: Metformin XR, 500 mg
* Drug: CANA/MET XR FDC, Formulation 1, 150 mg/1,000 mg
* Drug: CANA/MET XR FDC, Formulation 2, 150 mg/1,000 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must sign an informed consent document indicating they understand the purpose of the study and procedures Must have a body mass index (BMI) of between 18 and 30 kg/m2, inclusive Must have a body weight of not less than 50 kg - Must have a blood pressure between 90 and 140 mmHg inclusive, systolic, and no higher than 90 mmHg diastolic at screening Must have normal renal function and no evidence of kidney damage (including abnormalities in blood or urine tests) Exclusion Criteria: History of or current clinically significant medical illness Use of any prescription or nonprescription medication (including vitamins and herbal supplements) History of clinically significant allergies, especially known hypersensitivity or intolerance to drugs or lactose Known allergy to heparin or history of heparin induced thrombocytopenia Donated blood or blood products or had substantial loss of blood within 3 months before screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Each participant will receive a single dose of 1 tablet of canagliflozin (CANA), 300 mg, and 4 tablets of metformin extended release (MET XR), 500 mg each, administered together under fed conditions. | Drug: Canagliflozin, 300 mg<br>* Each tablet contains canagliflozin (CANA) of 300 mg to be taken orally (by mouth).<br>* Other names: INVOKANA™;Drug: Metformin XR, 500 mg<br>* Each tablet contains metformin extended release (MET XR), 500 mg, to be taken orally (by mouth).<br>* Other names: GLUMETZA®;|
| Experimental: Treatment B<br>Each participant will receive a single dose of 2 tablets of CANA/MET XR FDC, formulation 1, under fed conditions. | Drug: CANA/MET XR FDC, Formulation 1, 150 mg/1,000 mg<br>* Each tablet contains 150 mg of canagliflozin and 1,000 mg of metformin HCl granulate formulation 1, in release-controlling polymers to obtain the XR granulation, to be taken orally.<br>|
| Experimental: Treatment C<br>Each participant will receive a single dose of 2 tablets of CANA/MET XR FDC, formulation 2, under fed conditions. | Drug: CANA/MET XR FDC, Formulation 2, 150 mg/1,000 mg<br>* Each tablet contains 150 mg of canagliflozin and 1,000 mg of metformin HCl granulate formulation 2, in release-controlling polymers to obtain the XR granulation, to be taken orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of canagliflozin following administration of a single dose of study drug | Plasma concentrations of canagliflozin are used to evaluate how long canagliflozin stays in the body. | Predose, (before tablet intake) up to 72 hours after dose | 
| Plasma concentration of metformin following administration of a single dose of study drug | Plasma concentrations of metformin are used to evaluate how long metformin stays in the body. | Predose, up to 36 hours after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with adverse events as a measure of safety and tolerability |  | Screening, up to Day 10 of the follow-up period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers, Canagliflozin, Metformin, Type 2 diabetes mellitus