A Study to Compare the Pharmacodynamics of Canagliflozin and Dapagliflozin in Healthy Volunteers
- Registration Number
- NCT01877889
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
The purpose of this study is to compare the pharmacodynamics (ie, how the drug affects the body) of canagliflozin with the pharmacodynamics of dapagliflozin.
- Detailed Description
The study will be conducted as a 2-part study. Part 1 is an open-label pilot study (the investigator and the participants know the identity of the assigned treatment) in which 6 healthy volunteers will be given 300 mg of canagliflozin once daily for 4 consecutive days. The total study duration for each volunteer in Part 1 will be approximately 35 days (including a screening phase, an open-label treatment phase, and a follow-up phase). Part 2 will be a double-blind (neither the investigator nor volunteers know the identity of the assigned treatment), randomized (the treatment is assigned by chance), 2-period crossover study (all volunteers will receive each of the 2 treatments but in a different order) with a two-stage sequential group design.
Approximately 34 healthy volunteers will be participating in the first stage. After all the participants of the first stage will complete Part 2, and the results are analyzed, based on the first stage outcomes the study will be either terminated or will proceed to the second stage, which will be conducted using the same study method as in the first stage.
Potentially, up to 30 volunteers will participate in the second stage. A total number of participants in Part 2 will be up to 64.
Volunteers assigned to Treatment Sequence 1 will receive 10 mg of dapagliflozin once daily for 4 consecutive days (Period 1), and after a 12- to 14-day washout period (with no medication), 300 mg of canagliflozin once daily for 4 days (Period 2). Volunteers assigned to Treatment Sequence 2 will receive 300 mg of canagliflozin once daily for 4 days (Period 1), and after a 12- to 14-day washout period, 10 mg of dapagliflozin once daily for 4 consecutive days (Period 2). The total study duration for each volunteer in Part 2 will be up to approximately 65 days (including a screening phase, a baseline phase, a double-blind treatment phase, a washout period, and a follow-up phase).
Volunteers can participate in Part 1 or Part 2 of the study, but not in both parts. Canagliflozin and dapagliflozin are used for the treatment of type 2 diabetes mellitus.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 20 and 27 kg/m2 (inclusive), and body weight >= 50 kg at Screening
- Volunteers must have a systolic blood pressure between 90 and 140 mmHg, inclusive, and a diastolic blood pressure no higher than 90 mmHg (based upon an average of 3 blood pressure readings at Screening)
- Volunteers must be non-smokers
- Major surgery (eg, requiring general anesthesia) within 12 weeks before Screening, or planned during participation in the study, or within 2 weeks after the last dose of study drug administration, or volunteer will not have fully recovered from surgery during participation in the study; volunteers with planned surgical procedures to be conducted under local anesthesia may participate
- History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
- History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
- History of, or currently active illness, considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the volunteer from the study or that could interfere with the interpretation of the study results
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 2: Sequence 1 (Dapa/Cana) Canagliflozin Each volunteer will receive 10 mg of dapagliflozin once daily for 4 days (treatment period 1) followed by 300 mg of canagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period (with no medication). Part 2: Sequence 2 (Cana/Dapa) Canagliflozin Each volunteer will receive 300 mg of canagliflozin once daily for 4 days (treatment period 1) followed by 10 mg of dapagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period. Part 2: Sequence 2 (Cana/Dapa) Dapagliflozin Each volunteer will receive 300 mg of canagliflozin once daily for 4 days (treatment period 1) followed by 10 mg of dapagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period. Part 1: Cana Canagliflozin Each volunteer will receive 300 mg of canagliflozin once daily for 4 days. Part 2: Sequence 1 (Dapa/Cana) Dapagliflozin Each volunteer will receive 10 mg of dapagliflozin once daily for 4 days (treatment period 1) followed by 300 mg of canagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period (with no medication).
- Primary Outcome Measures
Name Time Method Between treatment difference in 24-hour mean renal threshold for glucose for canagliflozin (300 mg once daily for 4 days) compared to dapagliflozin (10 mg once daily for 4 days) Day 4 Renal threshold is defined as the plasma glucose concentration above which glucose is excreted in the urine.
- Secondary Outcome Measures
Name Time Method Percent change from baseline in postprandial glucose area under the curve at 0-2 hours post-dose on Day 4 following 300 mg of canagliflozin once daily for 4 days or 10 mg of dapagliflozin once daily for 4 days Day -10 (Baseline) and Day 4 Area under the concentration time curve (or area under the curve) is a measure of the body's exposure to glucose over a specific time period.
Number of volunteers with adverse events Up to Day 65 Adverse events will be used as a measure of safety and tolerability