Canagliflozin-Mealtime Insulin Rescue
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: canagliflozin 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
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.
Other Names:
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Placebo Comparator: placebo 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
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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 [24 weeks]
anti-hyperglycemic pill instead of insulin for at least one meal per day
- Number of patients with a continuing need for insulin 4 times per day [24 weeks]
no change from the original basal -bolus regimen
- Frequency and severity of hypoglycemia [24 weeks]
Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire
- Self monitoring and continuous monitoring blood glucose levels [24 weeks]
glycemic control and glycemic variability
Eligibility Criteria
Criteria
Inclusion Criteria:
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use of basal-bolus insulin
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onset of diabetes after age 30
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BMI less than 35
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eGFR at least 60 ml/mn
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Hb A1c 7.0-10.0%
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willingness to perform home glucose monitoring
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willingness to transmit glucose and medication information weekly
Exclusion Criteria:
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Type 1 diabetes
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Known peripheral artery disease
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Liver enzymes equal or more than 1.5 times the upper limit of normal
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Chronic heart failure NYHA class III or IV
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Current haemodialysis or peritoneal dialysis
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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
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Known or suspected hypersensitivity to trial products or related products
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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.
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Expected simultaneous participation in any other clinical trial of an investigational medicinal product.
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Receipt of any investigational medicinal product within 30 days before randomization
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Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell skin carcinoma)
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Any condition that in the investigator's opinion would make the subject unable to adhere to the trial visit schedule and procedures
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Known history of non-compliance to treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Atlanta VA Medical Center | Decatur | Georgia | United States | 30033 |
Sponsors and Collaborators
- Foundation for Atlanta Veterans Education and Research, Inc.
- Janssen Scientific Affairs, LLC
Investigators
- Principal Investigator: Lawrence S Phillips, MD, Atlanta VA Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- Bretzel RG, Nuber U, Landgraf W, Owens DR, Bradley C, Linn T. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008 Mar 29;371(9618):1073-84. doi: 10.1016/S0140-6736(08)60485-7. Erratum in: Lancet. 2008 Aug 30;372(9640):718.
- Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8.
- Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053.
- Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25.
- Home PD, Fritsche A, Schinzel S, Massi-Benedetti M. Meta-analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine. Diabetes Obes Metab. 2010 Sep;12(9):772-9. doi: 10.1111/j.1463-1326.2010.01232.x. Review.
- Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011 May;34(5):1164-70. doi: 10.2337/dc10-1915. Epub 2011 Mar 18.
- McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012 Sep;35(9):1897-901. doi: 10.2337/dc11-2054. Epub 2012 Jun 14.
- NICE-SUGAR Study Investigators, Finfer S, Liu B, Chittock DR, Norton R, Myburgh JA, McArthur C, Mitchell I, Foster D, Dhingra V, Henderson WR, Ronco JJ, Bellomo R, Cook D, McDonald E, Dodek P, Hébert PC, Heyland DK, Robinson BG. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012 Sep 20;367(12):1108-18.
- ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
- Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013 Aug;36(8):2154-61. doi: 10.2337/dc12-2391. Epub 2013 Feb 14.
- Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013 Sep;36(9):2508-15. doi: 10.2337/dc12-2491. Epub 2013 Apr 5. Erratum in: Diabetes Care. 2013 Dec;36(12):4172.
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