A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin as Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise
Overview
- Phase
- Phase 3
- Intervention
- Canagliflozin
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 678
- Primary Endpoint
- Change in HbA1c From Baseline to Week 26 (Main Study)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of 2 different doses of canagliflozin administered as monotherapy compared with placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.
Detailed Description
Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double blind (neither the patient or the study doctor will know the name of the assigned treatment), parallel-group, 3 arm (patients will be assigned to 1 of 3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients diagnosed with T2DM who are not achieving an adequate response from diet and exercise to control their diabetes. Approximately 450 patients with inadequate glycemic control with diet and exercise will receive once-daily treatment with canagliflozin 100 mg or 300 mg once daily for 52 weeks or 26 weeks of double-blind treatment with placebo followed by 26 weeks of sitagliptin 100 mg (sitagliptin is an antihyperglycemic agent that will allow patients randomized to the placebo group to improve glycemic control and remain in the study). Patients will participate in the study for approximately 60 to 68 weeks (referred to as the Main Study). The study will also include a High Glycemic Substudy in 50 to 100 patients with T2DM who have poorer glycemic control with diet and exercise. Patients in the substudy will be assigned to receive double-blind canagliflozin 100 mg or 300 mg for 26 weeks and the total duration of patient participatation in the substudy will be approximately 34 to 42 weeks. During treatment, if a patient's fasting blood sugar remains high despite treatment with study drug and reinforcement with diet and exercise, the patient will receive treatment with metformin (rescue therapy) consistent with local prescribing information. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single blind placebo for 1 or 2 weeks (wks) before randomization to the Main Study or the High Glycemic Substudy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All patients must have a diagnosis of T2DM
- •Patients in the main study must have a Hemoglobin A1c (HbA1c) between \>=7% and \<=10% and a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)
- •Patients in the High Glycemic Cohort Substudy must have an HbA1c between \>10% and \<=12% and a FPG \<=350 mg/dL (19.44 mmol/L)
Exclusion Criteria
- •History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening
Arms & Interventions
Canagliflozin 100 mg
Each patient will receive 100 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy).
Intervention: Canagliflozin
Canagliflozin 300 mg
Each patient will receive 300 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy).
Intervention: Canagliflozin
Placebo/Sitagliptin
In the Main Study, each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52.
Intervention: Placebo
Placebo/Sitagliptin
In the Main Study, each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52.
Intervention: Sitagliptin
Outcomes
Primary Outcomes
Change in HbA1c From Baseline to Week 26 (Main Study)
Time Frame: Day 1 (Baseline) and Week 26
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)
Time Frame: Day 1 (Baseline) and Week 26
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
Secondary Outcomes
- Percentage of Patients With HbA1c <7% at Week 26 (Main Study)(Week 26)
- Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Percent Change in Body Weight From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)(Week 26)
- Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)
- Percent Change in Triglycerides From Baseline to Week 26 (Main Study)(Day 1 (Baseline) and Week 26)
- Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)
- Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)
- Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)
- Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)
- Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)(Day 1 (Baseline) and Week 26)