Canagliflozin-Mealtime Insulin Rescue

Study Overview
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Brief Summary
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24-week, randomized, double blind, placebo-controlled trial to evaluate safety and efficacy of canagliflozin as compared with placebo in reducing the need for mealtime insulin in subjects with type 2 diabetes currently using a basal-bolus insulin regimen.

Detailed Description
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The Canagliflozin Mealtime Insulin Rescue study will enroll up to 40 subjects at the Atlanta VA Medical Center. Subjects will be screened and enter a 2-week run-in period during which they will switch to or continue on a diabetes treatment regimen of basal insulin before supper and aspart insulin before meals. Run-in will be useful in evaluating compliance to treatment and self-monitoring. After run-in, subjects will collect one week of baseline glycemic data with regular pre-meal and fasting glycemic levels using both finger stick testing and continuous glucose monitoring. Subjects will be randomized at Visit 3 to 100 mg of canagliflozin or placebo. If well tolerated, this dose will be increased to 300 mg of canagliflozin or placebo at Visit 4. Diabetes management will be assured through regular contact with the study team (weekly calls and clinic visits at Weeks 4, 8, 16 and 24). Management will be facilitated by diabetes management software. Self-monitoring and continuous glucose monitoring will be repeated at the end of study participation.

Official Title
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Canagliflozin-Mealtime Insulin Rescue

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: canagliflozin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: use of basal-bolus insulin onset of diabetes after age 30 BMI less than 35 eGFR at least 60 ml/mn Hb A1c 7.0-10.0% willingness to perform home glucose monitoring willingness to transmit glucose and medication information weekly Exclusion Criteria: Type 1 diabetes Known peripheral artery disease Liver enzymes equal or more than 1.5 times the upper limit of normal Chronic heart failure NYHA class III or IV Current haemodialysis or peritoneal dialysis End stage liver disease, defined as acute or chronic liver disease and recent history of one of the following: ascites, encephalopathy, variceal bleeding, bilirubin equal or greater than 2.0 mg/dL, albumin equal or less than 3.5 g/ dL, prothrombin time greater or equal to 4 seconds, INR greater than or equal to 1.7 or prior liver transplant Known or suspected hypersensitivity to trial products or related products Female of child-bearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using adequate contraceptive methods as required by law or local practice. Expected simultaneous participation in any other clinical trial of an investigational medicinal product. Receipt of any investigational medicinal product within 30 days before randomization Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell skin carcinoma) Any condition that in the investigator's opinion would make the subject unable to adhere to the trial visit schedule and procedures Known history of non-compliance to treatment.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: canagliflozin<br>Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. | Drug: canagliflozin<br>* Subjects randomized to active drug will receive canagliflozin 100 mg . If study drug well tolerated, dose will be increased to 300 mg canagliflozin at Visit 4.<br>* Other names: Invokana;|
| Placebo Comparator: placebo<br>Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. | Drug: placebo<br>* Subjects randomized to placebo will receive 100 mg placebo pill . If study drug well tolerated, dose will be increased to 300 mg placebo pill at Visit 4.<br>* Other names: inactive substance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who discontinue all pre-meal medications for at least one meal per day |  | 24 weeks | 
| Number of patients who replace mealtime insulin with an oral agent for at least one meal per day | anti-hyperglycemic pill instead of insulin for at least one meal per day | 24 weeks | 
| Number of patients with a continuing need for insulin 4 times per day | no change from the original basal -bolus regimen | 24 weeks | 
| Frequency and severity of hypoglycemia | Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire | 24 weeks | 
| Self monitoring and continuous monitoring blood glucose levels | glycemic control and glycemic variability | 24 weeks |