Clinical trial NCT01081834: The CANTATA-M (CANagliflozin Treatment and Trial Analysis - Monotherapy) Trial
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin as Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
Canagliflozin
Placebo
Hemoglobin A1c
Type 2 diabetes mellitus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-03-05
Enrollment: 678
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, safety, and tolerability of 2 different doses of canagliflozin administered as monotherapy compared with placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.

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), parallel-group, 3 arm (patients will be assigned to 1 of 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 diagnosed with T2DM who are not achieving an adequate response from diet and exercise to control their diabetes. Approximately 450 patients with inadequate glycemic control with diet and exercise will receive once-daily treatment with canagliflozin 100 mg or 300 mg once daily for 52 weeks or 26 weeks of double-blind treatment with placebo followed by 26 weeks of sitagliptin 100 mg (sitagliptin is an antihyperglycemic agent that will allow patients randomized to the placebo group to improve glycemic control and remain in the study). Patients will participate in the study for approximately 60 to 68 weeks (referred to as the Main Study). The study will also include a High Glycemic Substudy in 50 to 100 patients with T2DM who have poorer glycemic control with diet and exercise. Patients in the substudy will be assigned to receive double-blind canagliflozin 100 mg or 300 mg for 26 weeks and the total duration of patient participatation in the substudy will be approximately 34 to 42 weeks. During treatment, if a patient's fasting blood sugar remains high despite treatment with study drug and reinforcement with diet and exercise, the patient will receive treatment with metformin (rescue therapy) consistent with local prescribing information. 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 1 or 2 weeks (wks) before randomization to the Main Study or the High Glycemic Substudy.

Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of T2DM
* Patients in the main study must have a Hemoglobin A1c (HbA1c) between \>=7% and \<=10% and a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)
* Patients in the High Glycemic Cohort Substudy must have an HbA1c between \>10% and \<=12% and a FPG \<=350 mg/dL (19.44 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 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
Secondary outcomes:
measure: Percentage of Patients With HbA1c <7% at Week 26 (Main Study)
timeFrame: Week 26
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Body Weight From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Triglycerides From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)
timeFrame: Week 26
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)
timeFrame: Day 1 (Baseline) and Week 26
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Concord
country: United States
state: California
city: Greenbrae
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Northglenn
country: United States
state: Colorado
city: Springfield
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Baton Rouge
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: Meridian
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: West Seneca
country: United States
state: New York
city: Mooresville
country: United States
state: North Carolina
city: Perryopolis
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Taylors
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Horn
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Barranquilla
country: Colombia
city: Bogota
country: Colombia
city: Pärnu
country: Estonia
city: Tartu
country: Estonia
city: Viljandi
country: Estonia
city: Guatemala
country: Guatemala
city: Reykjavik
country: Iceland
city: Bangalore
country: India
city: Hyderabad
country: India
city: Nagpur
country: India
city: Busan
country: Korea, Republic of
city: Goyang-Si
country: Korea, Republic of
city: Jeonju-Si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Wonju-Si
country: Korea, Republic of
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius Lt
country: Lithuania
city: Vilnius
country: Lithuania
city: Kelantan
country: Malaysia
city: Kuala Lumpur N/A
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Aguascalientes
country: Mexico
city: Guadalajara
country: Mexico
city: Mex
country: Mexico
city: Monterrey
country: Mexico
city: Zapopan
country: Mexico
city: Makati
country: Philippines
city: Manila
country: Philippines
city: Marikina City
country: Philippines
city: Pasay
country: Philippines
city: Katowice
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Fajardo
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Targu Mures
country: Romania
city: Halfway
country: South Africa
city: Pretoria
country: South Africa
city: Alcala De Henares
country: Spain
city: Elche
country: Spain
city: Girona
country: Spain
city: Pozuelo De Alarcon
country: Spain
city: Göteborg
country: Sweden
city: Lund
country: Sweden
city: Malmö
country: Sweden
city: Skene
country: Sweden
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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.
citation: Stenlof K, Cefalu WT, Kim KA, Jodar E, Alba M, Edwards R, Tong C, Canovatchel W, Meininger G. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin. 2014 Feb;30(2):163-75. doi: 10.1185/03007995.2013.850066. Epub 2013 Oct 28.