Clinical trial NCT01106677: The CANTATA-D Trial (CANagliflozin Treatment and Trial Analysis - DPP-4 Inhibitor Comparator Trial)
Official title: A Randomized, Double-Blind, Placebo and Active-Controlled, 4-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 Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Type 2 diabetes mellitus
Canagliflozin
Placebo
Sitagliptin
Januvia
Metformin Immediate Release (IR)
Hemoglobin A1c
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 1284
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 canagliflozin compared with sitagliptin and placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (i.e., treatment with a single drug) 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 nor the study doctor will know the identity of assigned study drug), placebo- and active-controlled, parallel-group, 4-arm (4 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) and an active-control (sitagliptin 100 mg, an antihyperglycemic agent) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin Immediate Release (IR) to control their diabetes. Approximately 1,260 patients with T2DM who are receiving treatment with metformin IR and have inadequate glycemic (blood sugar) will receive once-daily treatment with canagliflozin (100 mg or 300 mg), sitagliptin 100 mg, or placebo capsules for 26 weeks (Period I) followed by another 26-weeks where patients treated with canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg will continue treatment for an additional 26 weeks and patients treated with placebo will be switched to active double-blind treatment with sitagliptin 100 mg capsules administered once-daily for 26 weeks (Period II). In addition, all patients will take protocol specified stable doses of metformin IR along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 71 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, metformin IR, and reinforcement with diet and exercise, the patient will receive treatment with glimepiride (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 sign 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. Patients will take single-blind placebo for 2 weeks before randomization. After randomization, patients in the study will take double-blind canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg for 52 weeks OR placebo for 26 weeks switched to double-blind treatment with sitaliptin 100 mg for 26 weeks.

Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of T2DM and be currently treated with metformin IR
* 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, 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: Change in 2-hour Post-prandial Glucose 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
measure: Change in HbA1c From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
measure: Change in Fasting Plasma Glucose (FPG) 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 Systolic Blood Pressure (SBP) From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
measure: Percent Change in Triglycerides From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
measure: Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
timeFrame: Day 1 (Baseline) and Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Fountain Valley
country: United States
state: California
city: National City
country: United States
state: California
city: Northridge
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Bradenton
country: United States
state: Florida
city: Brooksville
country: United States
state: Florida
city: Defuniak Springs
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Niceville
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Champaign
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Fishers
country: United States
state: Indiana
city: Franklin
country: United States
state: Indiana
city: West Des Moines
country: United States
state: Iowa
city: Wichita
country: United States
state: Kansas
city: Munfordville
country: United States
state: Kentucky
city: Portland
country: United States
state: Maine
city: Benzonia
country: United States
state: Michigan
city: Interlochen
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Picayune
country: United States
state: Mississippi
city: Florissant
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Mansfield
country: United States
state: New Jersey
city: New Hyde Park
country: United States
state: New York
city: Asheboro
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Kettering
country: United States
state: Ohio
city: Oregon City
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Tipton
country: United States
state: Pennsylvania
city: East Providence
country: United States
state: Rhode Island
city: Greer
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: New Braunfels
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Spokane
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Mendoza
country: Argentina
city: San Juan
country: Argentina
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sevlievo
country: Bulgaria
city: Sofia
country: Bulgaria
city: Barranquilla
country: Colombia
city: Bogota
country: Colombia
city: Medellin
country: Colombia
city: Beroun
country: Czech Republic
city: Pardubice
country: Czech Republic
city: Plzen
country: Czech Republic
city: Rychnov Nad Kneznou
country: Czech Republic
city: Tabor
country: Czech Republic
city: Tallinn
country: Estonia
city: Piraeus
country: Greece
city: Thessalonikis
country: Greece
city: Ahmedabad, Gujarat
country: India
city: Aurangabad
country: India
city: Bangalore, Karnataka
country: India
city: Bangalore
country: India
city: Belgaum
country: India
city: Coimbatore
country: India
city: Mumbai
country: India
city: Nagpur
country: India
city: Pune
country: India
city: Trivandrum
country: India
city: Daugavpils
country: Latvia
city: Limbazi
country: Latvia
city: Riga
country: Latvia
city: Talsi
country: Latvia
city: Kelantan
country: Malaysia
city: Kuala Lumpur N/A
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Pulau Pinang
country: Malaysia
city: Selangor
country: Malaysia
city: Culiacan
country: Mexico
city: Guadalajara
country: Mexico
city: Monterrey
country: Mexico
city: Queretaro
country: Mexico
city: Tampico
country: Mexico
city: Lima 1 Lima Lima
country: Peru
city: Leczyca
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Wroclaw
country: Poland
city: Zgierz
country: Poland
city: Aveiro
country: Portugal
city: Leiria
country: Portugal
city: Lisboa
country: Portugal
city: Portalegre
country: Portugal
city: San Juan
country: Puerto Rico
city: Chelyabinsk
country: Russian Federation
city: Dzerzhinsky Moscow Region
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Penza
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice
country: Slovakia
city: Sahy
country: Slovakia
city: Trebisov
country: Slovakia
city: Göteborg
country: Sweden
city: Stockholm
country: Sweden
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Konya
country: Turkey
city: Donetsk
country: Ukraine
city: Ivano Frankivsk
country: Ukraine
city: Kiev
country: Ukraine
city: Sumy
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zaporozhye
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC 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: Schernthaner G, Lavalle-Gonzalez FJ, Davidson JA, Jodon H, Vijapurkar U, Qiu R, Canovatchel W. Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes. Postgrad Med. 2016 Nov;128(8):725-730. doi: 10.1080/00325481.2016.1210988. Epub 2016 Jul 26.
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: Bailey RA, Vijapurkar U, Meininger G, Rupnow MF, Blonde L. Diabetes-Related Composite Quality End Point Attainment: Canagliflozin Versus Sitagliptin Based on a Pooled Analysis of 2 Clinical Trials. Clin Ther. 2015 May 1;37(5):1045-54. doi: 10.1016/j.clinthera.2015.02.020. Epub 2015 Mar 18.
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: 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: Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013 Dec;56(12):2582-92. doi: 10.1007/s00125-013-3039-1. Epub 2013 Sep 13.