Diabetes Mellitus, Type 2
Conditions
Keywords
Canagliflozin, Placebo, Metformin, Hemoglobin A1c, Type 2 diabetes mellitus
Brief summary
The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (ie, treatment with a single drug) and have inadequate glycemic (blood sugar) control.
Detailed description
This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study doctor will know the identity of assigned study drug), placebo-controlled, parallel-group,3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin compared to placebo (a capsule that is identical in appearance to canagliflozin but does not contain active drug) in patients with type 2 diabetes mellitus (T2DM) who are not achieving an adequate response from current antihyperglycemic therapy with metformin to control their diabetes. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with T2DM. Patients will take single-blind placebo capsules orally (by mouth) for 2 weeks before randomization. Patients will be randomly assigned canagliflozin or matching placebo, orally, twice daily, with 1 capsule taken with the morning meal and 1 capsule taken with the evening meal (2 capsules per day) and concurrent with metformin, if applicable, for up to 18 weeks. The dosing time of metformin should remain the same throughout the study.
Interventions
One canagliflozin 50-mg capsule taken orally twice daily with a meal for 18 weeks
DRUGPlacebo
1 placebo capsule taken orally twice daily with a meal for 18 weeks
DRUGCanagliflozin 150 mg
1 canagliflozin 150-mg capsule taken orally twice daily with a meal for 18 weeks
DRUGMetformin
The patient's stable daily dose of Metformin background therapy should be continued throughout the study.
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 80 Years
Healthy volunteers
No
Inclusion criteria
* All patients must have a diagnosis of T2DM and be currently treated with metformin * Patients in the study must have a HbA1c between \>=7 and \<=10.5% * Patients must have a fasting plasma glucose (FPG) \<270 mg/dL (15 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 18 | Day 1 (Baseline) and Week 18 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With HbA1c <7% at Week 18 | Week 18 | The table below shows the percentage of patients with HbA1c \<7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 | Day 1 (Baseline) and Week 18 | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Percent Change in Body Weight From Baseline to Week 18 | Day 1 (Baseline) and Week 18 | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. |
Countries
Canada, Czechia, Mexico, Romania, Russia, Slovakia, United States
Participant flow
Recruitment details
This study evaluated the efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin. The study was conducted between 27 June 2011 and 20 April 2012 and recruited patients from 60 study centers located in 7 countries worldwide.
Pre-assignment details
A total of 279 patients were randomly allocated to the 3 treatment arms in the study. All 279 patients received at least 1 dose of study drug and were included in the modified intent-to-treat analysis set which was used for the efficacy and safety analyses.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Each patient received matching placebo twice daily for 18 weeks. | 93 |
| Canagliflozin 50 mg Bid Each patient received 50 mg canagliflozin twice daily for 18 weeks. | 93 |
| Canagliflozin 150 mg Bid Each patient received 150 mg canagliflozin twice daily for 18 weeks. | 93 |
| Total | 279 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 7 |
| Overall Study | Creatinine or eGFR withdrawal criteria | 0 | 1 | 2 |
| Overall Study | Glycemic withdrawal criteria | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 |
| Overall Study | Other | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo | Canagliflozin 50 mg Bid | Canagliflozin 150 mg Bid | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 24 Participants | 18 Participants | 56 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 69 Participants | 75 Participants | 223 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 9.32 | 58.6 years STANDARD_DEVIATION 8.88 | 56.7 years STANDARD_DEVIATION 10.33 | 57.4 years STANDARD_DEVIATION 9.53 |
| Region Enroll CANADA | 17 participants | 11 participants | 12 participants | 40 participants |
| Region Enroll CZECH REPUBLIC | 2 participants | 4 participants | 6 participants | 12 participants |
| Region Enroll MEXICO | 10 participants | 12 participants | 10 participants | 32 participants |
| Region Enroll ROMANIA | 13 participants | 15 participants | 9 participants | 37 participants |
| Region Enroll RUSSIAN FEDERATION | 18 participants | 17 participants | 20 participants | 55 participants |
| Region Enroll SLOVAKIA | 10 participants | 9 participants | 11 participants | 30 participants |
| Region Enroll UNITED STATES | 23 participants | 25 participants | 25 participants | 73 participants |
| Sex: Female, Male Female | 47 Participants | 53 Participants | 49 Participants | 149 Participants |
| Sex: Female, Male Male | 46 Participants | 40 Participants | 44 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 93 | 0 / 93 | 0 / 93 |
| serious Total, serious adverse events | 1 / 93 | 0 / 93 | 3 / 93 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 18
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 18
Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when Week 18 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1c From Baseline to Week 18 | -0.01 Percent | Standard Error 0.069 |
| Canagliflozin 50 mg Bid | Change in HbA1c From Baseline to Week 18 | -0.45 Percent | Standard Error 0.07 |
| Canagliflozin 150 mg Bid | Change in HbA1c From Baseline to Week 18 | -0.61 Percent | Standard Error 0.069 |
p-value: <0.00195% CI: [-0.637, -0.251]ANCOVA
p-value: <0.00195% CI: [-0.792, -0.407]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 18
Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when Week 18 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 | 8.1 mg/dL | Standard Error 3.291 |
| Canagliflozin 50 mg Bid | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 | -15.5 mg/dL | Standard Error 3.327 |
| Canagliflozin 150 mg Bid | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 | -15.9 mg/dL | Standard Error 3.313 |
p-value: <0.00195% CI: [-32.78, -14.38]ANCOVA
p-value: <0.00195% CI: [-33.18, -14.83]ANCOVA
Secondary
Percentage of Patients With HbA1c <7% at Week 18
The table below shows the percentage of patients with HbA1c \<7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Time frame: Week 18
Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when Week 18 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c <7% at Week 18 | 31.5 Percentage of Participants |
| Canagliflozin 50 mg Bid | Percentage of Patients With HbA1c <7% at Week 18 | 47.8 Percentage of Participants |
| Canagliflozin 150 mg Bid | Percentage of Patients With HbA1c <7% at Week 18 | 57.1 Percentage of Participants |
p-value: 0.01395% CI: [1.21, 4.9]Regression, Logistic
p-value: <0.00195% CI: [1.68, 6.81]Regression, Logistic
Secondary
Percent Change in Body Weight From Baseline to Week 18
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 18
Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when Week 18 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Body Weight From Baseline to Week 18 | -0.6 Percent change | Standard Error 0.3 |
| Canagliflozin 50 mg Bid | Percent Change in Body Weight From Baseline to Week 18 | -2.8 Percent change | Standard Error 0.3 |
| Canagliflozin 150 mg Bid | Percent Change in Body Weight From Baseline to Week 18 | -3.2 Percent change | Standard Error 0.3 |
p-value: <0.00195% CI: [-3.1, -1.3]ANCOVA
p-value: <0.00195% CI: [-3.5, -1.7]ANCOVA