Clinical trial NCT00968812: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride
Official title: A Randomized, Double-Blind, 3-Arm Parallel-Group, 2-Year (104-Week), Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-28431754 Compared With Glimepiride in the Treatment of Subjects With Type 2 Diabetes Mellitus Not Optimally Controlled on Metformin Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Metformin
Glimepiride
Hemoglobin A1c
Type 2 diabetes mellitus
Canagliflozin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-08-31
Enrollment: 1452
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 demonstrate the efficacy, safety, and tolerability of canagliflozin (JNJ-28431754) compared with glimepiride in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin.

Detailed description: Type 2 diabetes mellitus (T2DM) is well recognized as a major public health problem that presents patients with a significant risk of complications including heart disease, retinopathy, nephropathy, and neuropathy. Various classes of orally administered antihyperglycemic agents have been developed for the treatment of diabetes and although individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients, thereby resulting in high rates of morbidity and mortality in the diabetic population. This is a randomized, double-blind, active comparator-controlled, 3-arm, parallel-group, multicenter study to demonstrate the efficacy, safety, and tolerability of canagliflozin compared with a sulfonylurea (glimepiride) in patients with T2DM, 18 to 80 years of age, inclusive, who are not optimally controlled on metformin monotherapy. The primary study hypothesis is that the study drug will be non-inferior to glimepiride as assessed by the change in hemoglobin A1c (HbA1c) from baseline. The patients will receive capsules taken by mouth of canagliflozin (either 100 or 300 mg), or glimepiride with a starting dosage of 1 mg, which will be increased to a maximum dose of 6 or 8 mg once daily for a total duration of 104 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients must have a diagnosis of type 2 diabetes
* Body mass index (BMI) \>=22 to \<=45 kg/m2, at screening
* Patients must be taking a stable dosage of metformin as monotherapy at screening
* Patients must have a HbA1c between \>=7% and \<=9.5% at Week 2
* Patients must have a fasting plasma glucose (FPG) \<=270 mg/dL (15 mmol/L) at Week -2

Exclusion Criteria:

* Patients having prior exposure or known contraindication or suspected hypersensitivity to JNJ-28431754, glimepiride, or metformin
* History of diabetic ketoacidosis or type 1 diabetes mellitus
* History of pancreas or beta-cell transplantation
* History of active proliferative diabetic retinopathy
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Renal disease requiring treatment with immunosuppressive therapy within the past 12 months before screening or a history of dialysis or renal transplant
* Taken thiazolidinedione therapy in the past 16 weeks before screening

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
Secondary outcomes:
measure: Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
measure: Percent Change in Body Weight From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
measure: Change in HbA1c From Baseline to Week 104
timeFrame: Baseline, Week 104
Other outcomes:
Locations:
city: Calera
country: United States
state: Alabama
city: Gilbert
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Jonesboro
country: United States
state: Arkansas
city: Buena Park
country: United States
state: California
city: Encinitas
country: United States
state: California
city: Fresno
country: United States
state: California
city: Lincoln
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Diego
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Chipley
country: United States
state: Florida
city: Marianna
country: United States
state: Florida
city: Oldsmar
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Perry
country: United States
state: Georgia
city: Nampa
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Vernon Hills
country: United States
state: Illinois
city: Valparaiso
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Elkridge
country: United States
state: Maryland
city: Bloomfield Hills
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Canal Fulton
country: United States
state: Ohio
city: Gallipolis
country: United States
state: Ohio
city: Mason
country: United States
state: Ohio
city: Perrysburg
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Yukon
country: United States
state: Oklahoma
city: Fleetwood
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: Pearland
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Danville
country: United States
state: Virginia
city: Olympia
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Wauwatosa
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Ciudad Autonoma De Buenos Aires
country: Argentina
city: Mar Del Plata
country: Argentina
city: Rosario
country: Argentina
city: Dimitrovgrad
country: Bulgaria
city: Kazanlak
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Chilliwack
country: Canada
state: British Columbia
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Mississauga
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Saskatoon
country: Canada
state: Saskatchewan
city: Quebec
country: Canada
city: San Jose
country: Costa Rica
city: San Pedro
country: Costa Rica
city: Aalborg
country: Denmark
city: Ballerup
country: Denmark
city: Vejle
country: Denmark
city: Vipperoed
country: Denmark
city: Helsinki
country: Finland
city: Kokkola
country: Finland
city: Kuopio
country: Finland
city: Oulu
country: Finland
city: Turku
country: Finland
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Duesseldorf
country: Germany
city: Hamburg
country: Germany
city: Mainz
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Bangalore
country: India
city: Chennai
country: India
city: Coimbatore
country: India
city: Hyderabad
country: India
city: Nagpur
country: India
city: Pune
country: India
city: Wardha
country: India
city: Beer Sheba
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Tel-Aviv
country: Israel
city: Zefat
country: Israel
city: Daegu
country: Korea, Republic of
city: Goyang-Si
country: Korea, Republic of
city: Gyeonggi-Do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Wonju-Si
country: Korea, Republic of
city: Wonju
country: Korea, Republic of
city: Ciudad De Mexico
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: Alesund
country: Norway
city: Oslo
country: Norway
city: Cebu
country: Philippines
city: Marikina City
country: Philippines
city: Pasay
country: Philippines
city: Quezon City
country: Philippines
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Kutno 001
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Zielona Gora
country: Poland
city: Ponce
country: Puerto Rico
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj
country: Romania
city: Galati
country: Romania
city: Ploiesti
country: Romania
city: Targu Mures
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Lubochna
country: Slovakia
city: Presov
country: Slovakia
city: Dnepropetrovsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Poltava
country: Ukraine
city: Ternopil
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Heerspink HJL, Perco P, Mulder S, Leierer J, Hansen MK, Heinzel A, Mayer G. Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia. 2019 Jul;62(7):1154-1166. doi: 10.1007/s00125-019-4859-4. Epub 2019 Apr 17.
citation: Garvey WT, Van Gaal L, Leiter LA, Vijapurkar U, List J, Cuddihy R, Ren J, Davies MJ. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018 Aug;85:32-37. doi: 10.1016/j.metabol.2018.02.002. Epub 2018 Feb 13.
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: Patel CA, Bailey RA, Vijapurkar U, Meininger G, Blonde L. A post-hoc analysis of the comparative efficacy of canagliflozin and glimepiride in the attainment of type 2 diabetes-related quality measures. BMC Health Serv Res. 2016 Aug 5;16(a):356. doi: 10.1186/s12913-016-1607-z.
citation: Blonde L, Stenlof K, Fung A, Xie J, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. Postgrad Med. 2016 May;128(4):371-80. doi: 10.1080/00325481.2016.1169894. Epub 2016 Apr 7.
citation: Leiter LA, Langslet G, Vijapurkar U, Davies MJ, Canovatchel W. Simultaneous Reduction in Both HbA1c and Body Weight with Canagliflozin Versus Glimepiride in Patients with Type 2 Diabetes on Metformin. Diabetes Ther. 2016 Jun;7(2):269-78. doi: 10.1007/s13300-016-0163-1. Epub 2016 Mar 16.
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: Leiter LA, Yoon KH, Arias P, Langslet G, Xie J, Balis DA, Millington D, Vercruysse F, Canovatchel W, Meininger G. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care. 2015 Mar;38(3):355-64. doi: 10.2337/dc13-2762. Epub 2014 Sep 9.
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.
citation: Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013 Sep 14;382(9896):941-50. doi: 10.1016/S0140-6736(13)60683-2. Epub 2013 Jul 12.