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

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 50 mg/500 mg) With Respect to the Individual Components of Canagliflozin (1 x 100 mg) and Metformin XR Tablet (2 x 500 mg) in Healthy Fed Subjects

Sponsors

Lead Sponsor: Janssen Research & Development, LLC

Source Janssen Research & Development, LLC
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 50 mg/500 mg) with respect to the individual components of canagliflozin (1 x 100 mg) and metformin XR tablet (2 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 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 of 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 (50 mg CANA/500 mg MET XR) and will be compared with the equal doses of the individual drugs: canagliflozin (1 x 100 mg tablet) and metformin XR (2 x 500 mg tablets). Thus, there will be 3 treatment periods in the study: Treatment A: "Reference" treatment of individual components. 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 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 (Days -22 to -2), an Open-Label Treatment Phase consisting of 3 single-dose Treatment Periods of 5 days each (Days -1 through 4) separated by a washout of 10 to 14 days between Day 1 of each Treatment Period, and a Follow-up Phase occurring 7 to 10 days after the last study-related procedure on Day 4 of Treatment Period 3. The total duration of the study will be about 70 days for each participant.

Overall Status Completed
Start Date February 2014
Completion Date April 2014
Primary Completion Date April 2014
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Plasma concentration of canagliflozin following the single dose of drug administration Predose, (before tablet intake) up to 72 hours afterdose
Plasma concentration of metformin following the single dose of drug administration Predose, up to 36 hours afterdose
Secondary Outcome
Measure 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
Enrollment 2
Condition
Intervention

Intervention Type: Drug

Intervention Name: Canagliflozin, 100 mg

Description: Each tablet contains canagliflozin (CANA) of 100 mg to be taken orally (by mouth).

Arm Group Label: Treatment A

Intervention Type: Drug

Intervention Name: Metformin XR, 500 mg

Description: Each tablet contains metformin extended release (MET XR), 500 mg, to be taken orally (by mouth).

Arm Group Label: Treatment A

Other Name: GLUMETZA®

Intervention Type: Drug

Intervention Name: CANA/MET XR FDC, Formulation 1, 50 mg/500 mg

Description: Each tablet contains 50 mg of canagliflozin and 500 mg of metformin HCl granulate, formulation 1, in release-controlling polymers to obtain the XR granulation, to be taken orally.

Arm Group Label: Treatment B

Intervention Type: Drug

Intervention Name: CANA/MET XR FDC, Formulation 2, 50 mg/500 mg

Description: Each tablet contains 50 mg of canagliflozin and 500 mg of metformin HCl granulate, formulation 2, in release-controlling polymers to obtain the XR granulation, to be taken orally.

Arm Group Label: Treatment C

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Location
Facility:
Location Countries

United States

Verification Date

June 2014

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 3
Arm Group

Label: Treatment A

Type: Experimental

Description: Each participant will receive a single dose of 1 tablet of canagliflozin (CANA), 100 mg, and 2 tablets of metformin extended release (MET XR), 500 mg, administered together under fed conditions.

Label: Treatment B

Type: Experimental

Description: Each participant will receive a single dose of 2 tablets of CANA/MET XR FDC, formulation 1, under fed conditions.

Label: Treatment C

Type: Experimental

Description: Each participant will receive a single dose of 2 tablets of CANA/MET XR FDC, formulation 2, under fed conditions.

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov