Clinical trial NCT01106690: The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone)
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 Pioglitazone Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Canagliflozin
Placebo
Sitagliptin (Januvia)
Metformin
Pioglitazone (Actos)
Hemoglobin A1c
Type 2 diabetes mellitus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 344
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 receving treatment with metformin and pioglitazone 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), 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 pioglitazone to control their diabetes. Approximately 360 patients with T2DM who are receiving combination therapy with metformin and pioglitazone will receive the addition of once-daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 26 weeks followed by a 26-week extension period where patients treated with canagliflozin (100 mg or 300 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, an antihyperglycemic agent administered once-daily for 26 weeks. In addition, all patients will take protocol specified stable doses of metformin and pioglitazone along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 78 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with glimepiride (rescue therapy) in accordance 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 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 capsules for 2 weeks before randomization. After randomization, patients will take double-blind canagliflozin (100 mg or 300 mg) for 52 weeks OR placebo for 26 weeks switched to double-blind sitagliptin 100 mg for 26 weeks.

Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of T2DM and be currently treated with PPAR gamma agent ((pioglitazone or rosiglitazone) and another anti-diabetes agent (metformin)
* Patients in the study must have a HbA1c between \>=7 and \<=10.5% and 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: Change in Homeostasis Model Assessment (HOMA2-%B) 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: Anniston
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Burlingame
country: United States
state: California
city: Encinitas
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Roseville
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Wes Hills
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Bartow
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Des Moines
country: United States
state: Iowa
city: Baton Rouge
country: United States
state: Louisiana
city: Chaska
country: United States
state: Minnesota
city: Picayune
country: United States
state: Mississippi
city: Billings
country: United States
state: Montana
city: Charlotte
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Dublin
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: Bensalem
country: United States
state: Pennsylvania
city: Bristol
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Grand Prairie
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: New Braunfels
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Federal Way
country: United States
state: Washington
city: Selah
country: United States
state: Washington
city: Bathurst
country: Canada
state: New Brunswick
city: Moncton
country: Canada
state: New Brunswick
city: Grand Falls-Windsor
country: Canada
state: Newfoundland and Labrador
city: Brampton
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Smiths Falls
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Drummondville
country: Canada
state: Quebec
city: Calgary
country: Canada
city: Mount Pearl
country: Canada
city: Truro
country: Canada
city: Kuopio
country: Finland
city: Oulu
country: Finland
city: Turku
country: Finland
city: Bondy Cedex
country: France
city: Le Creusot
country: France
city: Narbonne Cedex
country: France
city: Aschaffenburg
country: Germany
city: Mainz
country: Germany
city: Neuwied
country: Germany
city: Schkeuditz
country: Germany
city: Athens
country: Greece
city: Thessalonikis
country: Greece
city: Thessaloniki
country: Greece
city: Ahmedabad
country: India
city: Belgaum
country: India
city: Chennai
country: India
city: Coimbatore
country: India
city: Jaipur
country: India
city: Nagpur
country: India
city: Chihuahua
country: Mexico
city: Ciudad Juarez
country: Mexico
city: Durango
country: Mexico
city: Mexico
country: Mexico
city: Almería
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
city: Antrim
country: United Kingdom
city: Belfast
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC C. 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: 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: 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.