A Study of Effects of Canagliflozin as Add-on Therapy to Insulin in the Treatment of Participants With Type 1 Diabetes Mellitus (T1DM)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Phase 2, Double-blind, Placebo-controlled, Treat-to-Target, Parallel-group, 3-arm, Multicenter Study to Assess the Efficacy and Safety of Canagliflozin as Add-on Therapy to Insulin in the Treatment of Subjects With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Canagliflozin 100 mg
* Drug: Canagliflozin 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin 100 mg<br>Each participant will receive 100 mg of canagliflozin once daily for 18 weeks. | Drug: Canagliflozin 100 mg<br>* Canagliflozin capsule of 100 mg dose will be taken orally, before the first meal of the day.<br>|
| Experimental: Canagliflozin 300 mg<br>Each participant will receive 300 mg of canagliflozin once daily for 18 weeks. | Drug: Canagliflozin 300 mg<br>* Canagliflozin capsule of 300 mg dose will be taken orally, before the first meal of the day.<br>|
| Placebo Comparator: Placebo<br>Each participant will receive matching placebo once daily for 18 weeks | Drug: Placebo<br>* Matching placebo capsule will be taken orally, before the first meal of the day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 18 | 
| Percentage of Participants With Adverse Events |  | Up to 22 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 1, Canagliflozin, Continuous Glucose Monitoring