NCT02624908

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at below P25 for phase_4 diabetes-mellitus-type-2

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_4 diabetes-mellitus-type-2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 3, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 9, 2015

Completed
23 days until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2018

Completed
4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2022

Completed
Last Updated

August 15, 2022

Status Verified

August 1, 2022

Enrollment Period

2.5 years

First QC Date

December 3, 2015

Last Update Submit

August 12, 2022

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (5)

  • 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

Study Arms (2)

canagliflozin

ACTIVE COMPARATOR

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

placebo

PLACEBO COMPARATOR

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

Interventions

canagliflozinDRUG

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.

Also known as: Invokana
canagliflozin
placeboDRUG

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.

Also known as: inactive substance
placebo

Eligibility Criteria

Age30 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Related Publications (11)

  • ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden 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.

    PMID: 22686416BACKGROUND

  • 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.

    PMID: 18374840BACKGROUND

  • 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.

    PMID: 23564919BACKGROUND

  • 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.

    PMID: 23412078BACKGROUND

  • 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.

    PMID: 22111719BACKGROUND

  • 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.

    PMID: 20649629BACKGROUND

  • 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.

    PMID: 21421802BACKGROUND

  • 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, Hebert 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. doi: 10.1056/NEJMoa1204942.

    PMID: 22992074BACKGROUND

  • 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.

    PMID: 22699297BACKGROUND

  • 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.

    PMID: 18299315BACKGROUND

  • Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8. doi: 10.1001/jama.295.14.1707. No abstract available.

    PMID: 16609094BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsHeterocyclic Compounds, 1-RingHeterocyclic CompoundsGlucosidesGlycosidesCarbohydrates

Study Officials

  • Lawrence S Phillips, MD

    Atlanta VA Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 3, 2015

First Posted

December 9, 2015

Study Start

January 1, 2016

Primary Completion

July 1, 2018

Study Completion

December 1, 2022

Last Updated

August 15, 2022

Record last verified: 2022-08

Locations

US(1)