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 XR Tablet Co-administered With Canagliflozin in Healthy Fed and Fasted Participants
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02846506
- Lead Sponsor
- Janssen Research & Development, LLC
- 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 co-administered with canagliflozin in healthy fed and fasted participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
Inclusion Criteria
- 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 kilogram (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 mmHg, inclusive, systolic and no higher than 90 (Millimeter of mercury) mmHg diastolic at Screening or Day -1 of each Treatment Period
- Normal renal function evidenced by estimated glomerular filtration rate (eGFR) >=90 mL/min/1.73m2 using the Modification of Diet in Renal Disease Study (MDRD) equation as defined in the protocol
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Exclusion Criteria
- 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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence BACD Canagliflozin 50 mg 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. Treatment Sequence DCAB Canagliflozin 50 mg 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. Treatment Sequence DCAB Canagliflozin 100 mg 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. Treatment Sequence DCAB Metformin Extended Release (XR) 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. Treatment Sequence ADBC Canagliflozin 50 mg Participants will receive Treatment A (1 canagliflozin tablet 100 milligram (mg) and 1 canagliflozin tablet 50 mg along with 1 Extended Release (XR) tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, then Treatment D (1 XR fixed dose combination \[FDC\] tablet containing canagliflozin 150 mg and metformin 500 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 500 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) 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. Treatment Sequence ADBC Metformin Extended Release (XR) Participants will receive Treatment A (1 canagliflozin tablet 100 milligram (mg) and 1 canagliflozin tablet 50 mg along with 1 Extended Release (XR) tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, then Treatment D (1 XR fixed dose combination \[FDC\] tablet containing canagliflozin 150 mg and metformin 500 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 500 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) 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. Treatment Sequence CBDA Canagliflozin 50 mg 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. Treatment Sequence CBDA Canagliflozin 100 mg 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. Treatment Sequence CBDA Metformin Extended Release (XR) 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. Treatment Sequence BACD Canagliflozin 100 mg 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. Treatment Sequence BACD Metformin Extended Release (XR) 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. Treatment Sequence ADBC Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC] Participants will receive Treatment A (1 canagliflozin tablet 100 milligram (mg) and 1 canagliflozin tablet 50 mg along with 1 Extended Release (XR) tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, then Treatment D (1 XR fixed dose combination \[FDC\] tablet containing canagliflozin 150 mg and metformin 500 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 500 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) 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. Treatment Sequence BACD Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC] 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. Treatment Sequence CBDA Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC] 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. Treatment Sequence DCAB Canagliflozin and Metformin Extended Release (XR) Fixed Dose Combination [FDC] 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. Treatment Sequence ADBC Canagliflozin 100 mg Participants will receive Treatment A (1 canagliflozin tablet 100 milligram (mg) and 1 canagliflozin tablet 50 mg along with 1 Extended Release (XR) tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, then Treatment D (1 XR fixed dose combination \[FDC\] tablet containing canagliflozin 150 mg and metformin 500 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 500 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) 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.
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) 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 post-dose on Day 2 The Cmax is the maximum observed plasma concentration of metformin.
Area Under the Plasma Concentration-Time Curve From Time 0 to The Time of the Last Observed Quantifiable Concentration (AUClast) 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 post-dose on Day 2 The AUClast is the area under the plasma concentration-time curve from time 0 to the time of the last observed quantifiable concentration (Clast).
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinite Time [AUC (0-infinity)] 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 post-dose on Day 2 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.
- Secondary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Day -1 to End of study (up to 58 Days)