A Study to Assess the Bioequivalence of the Metformin Component of the Fixed Dose Combination Tablet of Canagliflozin and Metformin Extended Release With Respect to Metformin Extended Release Tablet Coadministered With Canagliflozin in Healthy Fed and Fasted Participants

NCT02851212 | Completed Phase 1

• 2 other identifiers: CR10820128431754DIA1076
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate bioequivalence of the metformin component of the Fixed Dose Combination (FDC) tablet compared with the metformin Extended Release (XR) tablet coadministered with canagliflozin in healthy fed and fasted participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax) of Metformin

  The Cmax is the maximum observed plasma concentration of metformin.

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, hr post-dose on Day 1; 24 hr postdose on Day 2

• Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration (AUClast) of Metformin

  The area under the plasma concentration time curve from time 0 to the time of the last observed quantifiable concentration (Clast).

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, hr post dose on Day 1; 24 hr post-dose on Day 2

• Area Under the Plasma Concentration Time Curve From Time 0 to Infinite Time [AUC (0-infinity)] of Metformin

  The AUC (0-infinity) is the area under the plasma concentration time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, hr post dose on Day 1; 24 hr postdose on Day 2

Secondary Outcomes (1)

• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  Day 1 to End of study (up to 58 Days)

Study Arms (4)

Treatment Sequence ADBC

EXPERIMENTAL

Participants will receive Treatment A (1 canagliflozin tablet 100 milligram (mg) and 1 canagliflozin tablet 50 mg along with two Extended Release (XR) tablets of metformin of each 500 mg orally under fed condition) on Day 1 of treatment period 1, then Treatment D (1 Extended Release (XR) fixed dose combination \[FDC\] tablet containing canagliflozin 150 mg and metformin 1000 mg orally under fasted condition) on Day 1 of treatment period 2, then Treatment B (1 XR FDC tablet containing canagliflozin 150 mg and metformin 1000 mg orally under fed condition) on Day 1 of treatment period 3, followed by Treatment C (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg and metformin XR two tablets of each 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 Extended Release (XR) Fixed Dose Combination [FDC]; Drug: Canagliflozin; Drug: Metformin Extended Release (XR)

Treatment Sequence BACD

EXPERIMENTAL

Participants will receive Treatment B on Day 1 of treatment period 1, then Treatment A on Day 1 of treatment period 2, then Treatment C on Day 1 of treatment period 3, followed by Treatment D on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.

Drug: Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC]; Drug: Canagliflozin; Drug: Metformin Extended Release (XR)

Treatment Sequence CBDA

EXPERIMENTAL

Participants will receive Treatment C Day 1 of treatment period 1, then Treatment B on Day 1 of treatment period 2, then Treatment D on Day 1 of treatment period 3, followed by Treatment A on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.

Drug: Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC]; Drug: Canagliflozin; Drug: Metformin Extended Release (XR)

Treatment Sequence DCAB

EXPERIMENTAL

Participants will receive Treatment D on Day 1 of treatment period 1, then Treatment C on Day 1 of treatment period 2, then Treatment A on Day 1 of treatment period 3, followed by Treatment B on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.

Drug: Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC]; Drug: Canagliflozin; Drug: Metformin Extended Release (XR)

Interventions

Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC] DRUG

Participants will receive 1 XR FDC tablet containing canagliflozin 150 mg and metformin 1000 mg orally under fed (Treatment B)or fasted condition (Treatment D) in a given treatment period as per treatment sequence.

Treatment Sequence ADBC; Treatment Sequence BACD; Treatment Sequence CBDA; Treatment Sequence DCAB

Canagliflozin DRUG

Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablets) under fed (part of Treatment A) or fasted condition (part of Treatment C) in a given treatment period as per treatment sequence.

Treatment Sequence ADBC; Treatment Sequence BACD; Treatment Sequence CBDA; Treatment Sequence DCAB

Metformin Extended Release (XR) DRUG

Participants will receive metformin XR 500 mg tablet orally under fed (part of Treatment A) or fasted condition (part of Treatment C) in a given treatment period as per treatment sequence.

Treatment Sequence ADBC; Treatment Sequence BACD; Treatment Sequence CBDA; Treatment Sequence DCAB

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
• Before randomization, a woman must be either Not of childbearing potential or of childbearing potential and agrees to use a highly effective method of contraception (failure rate of less than \[\<\]1 percent \[%\] per year when used consistently and correctly) throughout the study
• All women must have a negative urine pregnancy test at Screening and on Day -1 of each Treatment Period
• Body mass index (BMI) (weight \[kg\]/height\^2 \[m\]\^2) between 18 and 30 kg/m\^2 (inclusive), and body weight not less than 50 kg
• Blood pressure (an average of 3 measurements done after the participant is sitting for 5 minutes and with at least 5 minutes between measurements) between 90 and 140 (mercury of millimeter) mmHg, inclusive, systolic and no higher than 90 mmHg diastolic at Screening or Day -1 of each Treatment Period
• Normal renal function evidenced by estimated glomerular filtration rate (eGFR) greater than or equal to (\>=90) milliliters per minute (mL/min)/1.73m\^2 using the Modification of Diet in Renal Disease Study (MDRD) equation as defined in the protocol

You may not qualify if:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis as assessed by the investigator at Screening or Day -1 of the first Treatment Period
• Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) (Screening only) as assessed by the investigator at Screening or on Day -1 of the first Treatment Period as deemed appropriate by the investigator
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, hormonal contraceptives and hormonal replacement therapy within 14 days before the first dose of the study drug is scheduled
• History of, or a reason to believe a participant has a history of drug or alcohol abuse within the past 5 years

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, United States

Location

MeSH Terms

Interventions

Canagliflozin

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 1, 2016
• Study Start: August 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: December 2, 2016

Record last verified: 2016-12

Locations

US (1)