Clinical trial NCT01106625: The CANTATA-MSU Trial (CANagliflozin Treatment And Trial Analysis - Metformin and SUlphonylurea)
Official title: A Randomized, Double-Blind, Placebo-Controlled, 3-Arm, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Sulphonylurea Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Canagliflozin
Placebo
Metformin
Sulphonylurea
Hemoglobin A1c
Type 2 diabetes mellitus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 469
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control.

Detailed description: Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), placebo-controlled, parallel-group, 3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin and sulphonylurea to control their diabetes. Approximately 450 patients with T2DM who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 52 weeks (includes 26 weeks of double-blind treatment followed by a 26-week extension period). In addition, all patients will take protocol-specified stable doses of metformin and sulphonylurea for the duration of the study. Patients will participate in the study for approximately 59 to 72 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with insulin (rescue therapy) consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is to assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. All patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double-blind canagliflozin (100 mg or 300 mg) or matching placebo for 52 weeks.

Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of T2DM and be currently treated with metformin and sulphonylurea
* Patients in the study must have a HbA1c between \>=7 and \<=10.5%
* Patients must have a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)

Exclusion Criteria:

* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
Secondary outcomes:
measure: Percentage of Patients With HbA1c <7% at Week 26
timeFrame: Week 26
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Body Weight From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Triglycerides From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Little Rock
country: United States
state: Alaska
city: Phoenix
country: United States
state: Arizona
city: Chino
country: United States
state: California
city: Fair Oaks
country: United States
state: California
city: Roseville
country: United States
state: California
city: Wes Hills
country: United States
state: California
city: Waterbury
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: St Petersburg
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Reisterstown
country: United States
state: Maryland
city: Olive Branch
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Westfield
country: United States
state: New York
city: Greenville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Harleysville
country: United States
state: Pennsylvania
city: Levittown
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Bryan
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Desoto
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: South Burlington
country: United States
state: Vermont
city: Wenatchee
country: United States
state: Washington
city: Freemantle
country: Australia
city: Heidelberg Heights
country: Australia
city: Meadowbrook
country: Australia
city: Nedlands
country: Australia
city: Wollongong
country: Australia
city: Aalst
country: Belgium
city: Bonheiden
country: Belgium
city: Edegem
country: Belgium
city: Leuven
country: Belgium
city: Corbeil Essonnes
country: France
city: La Rochelle
country: France
city: Le Creusot
country: France
city: Poitiers
country: France
city: Venissieux
country: France
city: Guatemala
country: Guatemala
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Győr
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Tel Aviv
country: Israel
city: Guadalajara
country: Mexico
city: Monterrey
country: Mexico
city: Carolina
country: Puerto Rico
city: Trujillo Alto
country: Puerto Rico
city: Arkhangelsk
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Alicante
country: Spain
city: Almeria
country: Spain
city: Malaga
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Belfast
country: United Kingdom
city: Bolton
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Cai J, Delahanty LM, Akapame S, Slee A, Traina S. Impact of Canagliflozin Treatment on Health-Related Quality of Life among People with Type 2 Diabetes Mellitus: A Pooled Analysis of Patient-Reported Outcomes from Randomized Controlled Trials. Patient. 2018 Jun;11(3):341-352. doi: 10.1007/s40271-017-0290-4.
citation: Davies MJ, Merton K, Vijapurkar U, Yee J, Qiu R. Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data. Cardiovasc Diabetol. 2017 Mar 21;16(1):40. doi: 10.1186/s12933-017-0517-7.
citation: Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017 Feb 27;16(1):29. doi: 10.1186/s12933-017-0511-0.
citation: Gilbert RE, Mende C, Vijapurkar U, Sha S, Davies MJ, Desai M. Effects of Canagliflozin on Serum Magnesium in Patients With Type 2 Diabetes Mellitus: A Post Hoc Analysis of Randomized Controlled Trials. Diabetes Ther. 2017 Apr;8(2):451-458. doi: 10.1007/s13300-017-0232-0. Epub 2017 Feb 14.
citation: Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017 Mar;33(3):553-562. doi: 10.1080/03007995.2016.1271780. Epub 2017 Jan 4.
citation: John M, Cerdas S, Violante R, Deerochanawong C, Hassanein M, Slee A, Canovatchel W, Hamilton G. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016 Sep;70(9):775-85. doi: 10.1111/ijcp.12868.
citation: Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
citation: Lavalle-Gonzalez FJ, Eliaschewitz FG, Cerdas S, Chacon Mdel P, Tong C, Alba M. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America. Curr Med Res Opin. 2016;32(3):427-39. doi: 10.1185/03007995.2015.1121865. Epub 2016 Jan 14.
citation: Blonde L, Woo V, Mathieu C, Yee J, Vijapurkar U, Canovatchel W, Meininger G. Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials. Curr Med Res Opin. 2015 Nov;31(11):1993-2000. doi: 10.1185/03007995.2015.1082991. Epub 2015 Sep 28.
citation: Gavin JR 3rd, Davies MJ, Davies M, Vijapurkar U, Alba M, Meininger G. The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(9):1693-702. doi: 10.1185/03007995.2015.1067192. Epub 2015 Sep 4.
citation: Cefalu WT, Stenlof K, Leiter LA, Wilding JP, Blonde L, Polidori D, Xie J, Sullivan D, Usiskin K, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia. 2015 Jun;58(6):1183-7. doi: 10.1007/s00125-015-3547-2. Epub 2015 Mar 27.
citation: Weir MR, Januszewicz A, Gilbert RE, Vijapurkar U, Kline I, Fung A, Meininger G. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82. doi: 10.1111/jch.12425. Epub 2014 Oct 20.
citation: Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med. 2014 May;126(3):16-34. doi: 10.3810/pgm.2014.05.2753.
citation: Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.
citation: Sinclair A, Bode B, Harris S, Vijapurkar U, Mayer C, Fung A, Shaw W, Usiskin K, Desai M, Meininger G. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord. 2014 Apr 18;14:37. doi: 10.1186/1472-6823-14-37.
citation: Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia. 2014 May;57(5):891-901. doi: 10.1007/s00125-014-3196-x. Epub 2014 Mar 1.
citation: Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.