Canagliflozin-Mealtime Insulin Rescue

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Canagliflozin-Mealtime Insulin Rescue

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02624908
• Other study ID #: 28431754DIA4008
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: December 2022

Study information

• Verified date: August 2022
• Source: Foundation for Atlanta Veterans Education and Research, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2022
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Atlanta VA Medical Center	Decatur	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Foundation for Atlanta Veterans Education and Research, Inc.	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who discontinue all pre-meal medications for at least one meal per day		24 weeks
Primary	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
Primary	Number of patients with a continuing need for insulin 4 times per day	no change from the original basal -bolus regimen	24 weeks
Primary	Frequency and severity of hypoglycemia	Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire	24 weeks
Primary	Self monitoring and continuous monitoring blood glucose levels	glycemic control and glycemic variability	24 weeks