Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus, Type 2, Canagliflozin, Hemoglobin A1c, Metformin, Sitagliptin, T2DM, JNJ-28431754
Brief summary
The purpose of this study is to assess the effect of canagliflozin (JNJ-28431754) compared to placebo in the treatment of participants with Type 2 Diabetes Mellitus (T2DM), who have inadequate glycemic control on maximally or near-maximally effective doses of metformin and sitagliptin.
Detailed description
This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a study drug, to test whether the study drug has a real effect), multicenter study of efficacy, safety, and tolerability of canagliflozin in participants with T2DM, who have inadequate glycemic (blood sugar) control on maximally or near-maximally effective doses of metformin \>=1500 mg/day and sitagliptin 100 mg/day. Approximately 200 participants will be randomly assigned to 1 of 2 treatment groups in 1:1 ratio for 26 weeks. During the study the participants will be also provided with diet and exercise counseling (standardized non-pharmacological therapy).
Interventions
One 100 mg capsule taken orally (by mouth) once daily.
One 300 mg capsule taken orally (by mouth) once daily.
DRUGPlacebo
One placebo capsule taken orally (by mouth) once daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Must have a diagnosis of type 2 diabetes mellitus * Must have a screening HbA1c of \>=7.5% to \<=10.5% * Must be on metformin \>=1500 mg/day and sitagliptin 100 mg/day (or equivalent fixed dose combination) at a stable dose for at least 12 weeks before screening
Exclusion criteria
* History of diabetic ketoacidosis or T1DM, hereditary glucose-galactose malabsorption or primary renal glycosuria * A myocardial infarction, unstable angina, revascularization procedure or cerebrovascular accident within 12 weeks before screening * eGFR \<60 ml/min/1.73m2, or serum creatinine \>=1.4 mg/dL for men and \>=1.3 mg/dL for women * Known significant liver disease (eg, acute hepatitis, chronic active hepatitis, cirrhosis) * Major surgery (ie, requiring general anesthesia) within 12 weeks before screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Baseline and Week 26 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Baseline and Week 26 |
| Percent Change From Baseline in Body Weight at Week 26 | Baseline and Week 26 |
| Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26 | Week 26 |
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 26 | Baseline and Week 26 |
Countries
Australia, Canada, France, Germany, United States
Participant flow
Pre-assignment details
One participant was randomized at 2 different sites (once to placebo and once to canagliflozin) and was therefore counted twice in the total number of randomized participants. The participant was withdrawn from the study and not included in any efficacy or safety analyses.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants administered with placebo (inactive medication) once daily for 26 weeks. | 106 |
| Canagliflozin Participants administered canagliflozin (JNJ-28431754) 100 milligram (mg) titratable to 300 mg once daily for 26 weeks. | 107 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Potential misconduct,GCPcompliance issue | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 8 |
Baseline characteristics
| Characteristic | Placebo | Canagliflozin | Total |
|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 10.14 | 57.4 years STANDARD_DEVIATION 9.28 | 57.4 years STANDARD_DEVIATION 9.69 |
| Gender Female | 51 Participants | 41 Participants | 92 Participants |
| Gender Male | 55 Participants | 66 Participants | 121 Participants |
| Region of Enrollment Australia | 13 participants | 22 participants | 35 participants |
| Region of Enrollment Canada | 16 participants | 23 participants | 39 participants |
| Region of Enrollment France | 10 participants | 6 participants | 16 participants |
| Region of Enrollment Germany | 16 participants | 13 participants | 29 participants |
| Region of Enrollment United States | 51 participants | 43 participants | 94 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 108 | 18 / 108 |
| serious Total, serious adverse events | 2 / 108 | 2 / 108 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
Time frame: Baseline and Week 26
Population: mITT population included all randomized participants who received at least 1 dose of double-blind study drug. A total of 3 participants were excluded from the mITT population due to potential misconduct and GCP compliance issues. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.01 percentage of glycosylated hemoglobin | Standard Error 0.119 |
| Canagliflozin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.91 percentage of glycosylated hemoglobin | Standard Error 0.113 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Time frame: Baseline and Week 26
Population: mITT population included all randomized participants who received at least 1 dose of double-blind study drug. A total of 3 participants were excluded from the mITT population due to potential misconduct and GCP compliance issues. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -0.14 millimoles per liter | Standard Error 0.281 |
| Canagliflozin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -1.65 millimoles per liter | Standard Error 0.264 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) at Week 26
Time frame: Baseline and Week 26
Population: mITT population included all randomized participants who received at least 1 dose of double-blind study drug. A total of 3 participants were excluded from the mITT population due to potential misconduct and GCP compliance issues. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Week 26 | 0.09 millimeter of mercury (mmHg) | Standard Error 1.123 |
| Canagliflozin | Change From Baseline in Systolic Blood Pressure (SBP) at Week 26 | -5.76 millimeter of mercury (mmHg) | Standard Error 1.078 |
Secondary
Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26
Time frame: Week 26
Population: mITT population included all randomized participants who received at least 1 dose of double-blind study drug. A total of 3 participants were excluded from the mITT population due to potential misconduct and GCP compliance issues. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26 | 12.2 percentage of participants |
| Canagliflozin | Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26 | 32.3 percentage of participants |
Secondary
Percent Change From Baseline in Body Weight at Week 26
Time frame: Baseline and Week 26
Population: mITT population included all randomized participants who received at least 1 dose of double-blind study drug. A total of 3 participants were excluded from the mITT population due to potential misconduct and GCP compliance issues. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight at Week 26 | -1.60 percent change | Standard Error 0.337 |
| Canagliflozin | Percent Change From Baseline in Body Weight at Week 26 | -3.35 percent change | Standard Error 0.324 |