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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02077803
First received: February 28, 2014
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to assess the bioequivalence (similarity of the drug amount in blood among the formulations) 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/1000 mg) with respect to the individual components of canagliflozin (1 x 100 mg) and metformin XR tablet (4 x 500 mg) in healthy fed participants.


Condition Intervention Phase
Healthy
Drug: Canagliflozin, 100 mg
Drug: Metformin XR, 500 mg
Drug: CANA/MET XR FDC, Formulation 1, 50 mg/1000 mg
Drug: CANA/MET XR FDC, Formulation 2, 50 mg/1000 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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 50 mg/1,000 mg) With Respect to the Individual Components of Canagliflozin (1 x 100 mg) and Metformin XR Tablet (4 x 500 mg) in Healthy Fed Subjects

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Plasma concentration of canagliflozin following the single dose of drug administration [ Time Frame: Day 1 to Day 2 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours postdose); Day 3 (48 hour); and Day 4 ] [ Designated as safety issue: No ]
    Plasma concentrations of canagliflozin are used to evaluate how long canagliflozin stays in the body.

  • Plasma concentration of metformin following the single dose of drug administration [ Time Frame: Day 1 to Day 2 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, and 30 hours postdose); and Day 3 (36 hours) ] [ Designated as safety issue: No ]
    Plasma concentrations of metformin are used to evaluate how long it stays in the body.


Secondary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to Day 10 of the follow-up period ] [ Designated as safety issue: Yes ]

Enrollment: 47
Study Start Date: March 2014
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
Each participant will receive a single dose of 1 tablet of canagliflozin (CANA), 100 mg, and 4 tablets of metformin extended release (MET XR), 500 mg, administered together under fed conditions.
Drug: Canagliflozin, 100 mg
Each tablet contains canagliflozin (CANA) of 100 mg to be taken orally (by mouth).
Drug: Metformin XR, 500 mg
Each tablet contains metformin extended release (MET XR), 500 mg, to be taken orally (by mouth).
Experimental: Treatment B
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, 50 mg/1000 mg
Each tablet contains 50 mg of canagliflozin and 1000 mg of metformin HCl granulate, formulation 1, to be taken orally.
Experimental: Treatment C
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, 50 mg/1000 mg
Each tablet contains 50 mg of canagliflozin and 1000 mg of metformin HCl granulate, formulation 2, to be taken orally.

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 Fixed Dose Combination (FDC) tablets of canagliflozin (CANA) and metformin extended release (MET XR) 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/1,000 mg MET XR) and will be compared with equal doses of the individual drugs: canagliflozin (1 x 100 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. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02077803

Locations
United States, Arizona
Tempe, Arizona, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02077803     History of Changes
Other Study ID Numbers: CR103257, 28431754DIA1062
Study First Received: February 28, 2014
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Healthy
Canagliflozin
Metformin
Type 2 diabetes mellitus
Bioequivalence
GLUMETZA®

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014