Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1, Canagliflozin, Continuous Glucose Monitoring
Brief summary
The purpose of this study is to assess the effects of administration of canagliflozin 100 mg and 300 mg, compared with placebo as an addition to insulin therapy for the treatment of Type 1 Diabetes Mellitus (T1DM).
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 medication to test whether the medication has a real effect) parallel-group, multicenter study of canagliflozin as an addition to insulin therapy for participants with type 1 diabetes mellitus and inadequate glycemic control. Approximately 330 participants will be randomly assigned in a 1:1:1 ratio to either canagliflozin 100 mg, canagliflozin 300 mg, or placebo groups. About 90 participants (30 per treatment group) will be selected for a substudy with a purpose of a continuous glucose monitoring (CGM) assessment for 7 days at baseline and 7 days at the end of treatment. The total duration of the participation will be about 22 weeks, during which participants will need to return to investigational sites for approximately 9 visits. During the study participants will receive advice on treatment of hypoglycemia and diabetic ketoacidosis (DKA), as well as on compliance with diet and exercise.
Interventions
Canagliflozin capsule of 100 mg dose will be taken orally, before the first meal of the day.
Canagliflozin capsule of 300 mg dose will be taken orally, before the first meal of the day.
DRUGPlacebo
Matching placebo capsule will be taken orally, before the first meal of the day.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must have type 1 diabetes mellitus (T1DM) for at least 1 year * Must have have inadequate glycemic control (as defined by glycosylated hemoglobin level of \>= 7.0% to \<= 9.0%) on basal plus bolus insulin at screening * Must have body mass index 21 to 35 kg/m2 inclusive * Must be on a total daily dose of insulin \>= 0.6 IU/kg at screening * Must be on a stable insulin regimen for at least 8 weeks prior to screening
Exclusion criteria
* History of T2DM, pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy * Severe hypoglycemia (defined as an event required assistance from another person, or which resulted in seizure or loss of consciousness) within 6 months prior to study start * Diabetic ketoacidosis within 6 months prior to study start * History of hereditary glucose-galactose malabsorption or primary renal glycosuria * An ongoing, inadequately controlled thyroid disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | Week 18 | Clinical response at Weeks 18 was assessed by the percentage of participants with Hemoglobin A1c (HbA1c) reduction greater than or equal to 0.4 % and had no increase in body weight. |
| Percentage of Participants With Adverse Events | Up to 22 Weeks | — |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 614 participants were screened and 352 subjects (57.3%) were randomized to study drug. One subject randomized to placebo did not take any study drug and withdrew consent on the day of randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received canagliflozin matching placebo capsules once daily for 18 weeks. | 117 |
| Canagliflozin 100 Milligram (mg) Participants received 100 mg of canagliflozin capsules once daily for 18 weeks. | 117 |
| Canagliflozin 300 mg Participants received 300 mg of canagliflozin capsules once daily for 18 weeks. | 117 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 |
| Overall Study | eGFR Withdrawal Criteria | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 | 2 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Participant in Poor Compliance | 1 | 0 | 1 |
| Overall Study | Participant wishes to discontinue | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Canagliflozin 100 Milligram (mg) | Canagliflozin 300 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 117 Participants | 115 Participants | 115 Participants | 347 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 11.9 | 42 years STANDARD_DEVIATION 11.6 | 42.8 years STANDARD_DEVIATION 10.96 | 42.3 years STANDARD_DEVIATION 11.47 |
| Region Enroll Canada | 24 participants | 19 participants | 20 participants | 63 participants |
| Region Enroll United Stats | 93 participants | 98 participants | 97 participants | 288 participants |
| Sex: Female, Male Female | 54 Participants | 48 Participants | 52 Participants | 154 Participants |
| Sex: Female, Male Male | 63 Participants | 69 Participants | 65 Participants | 197 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 | 32 / 117 | 36 / 117 | 43 / 117 |
| serious Total, serious adverse events | 0 / 117 | 9 / 117 | 8 / 117 |
Outcome results
Primary
Percentage of Participants With Adverse Events
Time frame: Up to 22 Weeks
Population: Safety Analysis Set included all randomized participants who took at least 1 dose of double-blind study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events | 54.7 percentage of participants |
| Canagliflozin 100 Milligram (mg) | Percentage of Participants With Adverse Events | 55.6 percentage of participants |
| Canagliflozin 300 mg | Percentage of Participants With Adverse Events | 67.5 percentage of participants |
Primary
Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight
Clinical response at Weeks 18 was assessed by the percentage of participants with Hemoglobin A1c (HbA1c) reduction greater than or equal to 0.4 % and had no increase in body weight.
Time frame: Week 18
Population: Modified intent-to-treat analysis set included all randomized participants who took at least 1 dose of double-blind study drug. 'N (Number of Participants Analyzed)' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | Yes | 14.5 percentage of participants |
| Placebo | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | No | 85.5 percentage of participants |
| Canagliflozin 100 Milligram (mg) | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | Yes | 36.9 percentage of participants |
| Canagliflozin 100 Milligram (mg) | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | No | 63.1 percentage of participants |
| Canagliflozin 300 mg | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | Yes | 41.4 percentage of participants |
| Canagliflozin 300 mg | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight | No | 58.6 percentage of participants |