The CANTATA-M (CANagliflozin Treatment and Trial Analysis - Monotherapy) Trial

NCT ID: NCT01081834

Last Updated: 2017-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 678 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-03-31

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Canagliflozin 100 mg

Each patient will receive 100 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy).

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks (Main Study) or 26 weeks (High Glycemic Substudy)

Canagliflozin 300 mg

Each patient will receive 300 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy).

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks (Main Study) or 26 weeks (High Glycemic Substudy)

Placebo/Sitagliptin

In the Main Study, each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

One matching placebo capsule orally once daily for 26 weeks (Main Study)

Sitagliptin

Intervention Type: DRUG

One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 (Main Study)

Interventions

Canagliflozin

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks (Main Study) or 26 weeks (High Glycemic Substudy)

Intervention Type: DRUG

Placebo

One matching placebo capsule orally once daily for 26 weeks (Main Study)

Intervention Type: DRUG

Sitagliptin

One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 (Main Study)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Phoenix, Arizona, United States

Concord, California, United States

Greenbrae, California, United States

Los Angeles, California, United States

Spring Valley, California, United States

Colorado Springs, Colorado, United States

Denver, Colorado, United States

Northglenn, Colorado, United States

Springfield, Illinois, United States

Evansville, Indiana, United States

Baton Rouge, Louisiana, United States

Metairie, Louisiana, United States

Meridian, New Jersey, United States

Albuquerque, New Mexico, United States

New York, New York, United States

West Seneca, New York, United States

Mooresville, North Carolina, United States

Perryopolis, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Taylors, South Carolina, United States

Dallas, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Norfolk, Virginia, United States

Horn, , Austria

Salzburg, , Austria

Vienna, , Austria

Barranquilla, , Colombia

Bogotá, , Colombia

Pärnu, , Estonia

Tartu, , Estonia

Viljandi, , Estonia

Guatemala City, , Guatemala

Reykjavik, , Iceland

Bangalore, , India

Hyderabad, , India

Nagpur, , India

Kaunas, , Lithuania

Klaipėda, , Lithuania

Šiauliai, , Lithuania

Vilnius, , Lithuania

Vilnius Lt, , Lithuania

Kelantan, , Malaysia

Kuala Lumpur, , Malaysia

Aguascalientes, , Mexico

Guadalajara, , Mexico

Mexico City, , Mexico

Monterrey, , Mexico

Zapopan, , Mexico

Makati, , Philippines

Manila, , Philippines

Marikina City, , Philippines

Pasay, , Philippines

Katowice, , Poland

Torun, , Poland

Warsaw, , Poland

Fajardo, , Puerto Rico

Ponce, , Puerto Rico

San Juan, , Puerto Rico

Baia Mare, , Romania

Brasov, , Romania

Bucharest, , Romania

Târgu Mureş, , Romania

Halfway, , South Africa

Pretoria, , South Africa

Busan, , South Korea

Goyang-si, , South Korea

Jeonju, , South Korea

Seoul, , South Korea

Wŏnju, , South Korea

Alcalá de Henares, , Spain

Elche, , Spain

Girona, , Spain

Pozuelo de Alarcón, , Spain

Gothenburg, , Sweden

Lund, , Sweden

Malmo, , Sweden

Skene, , Sweden

Countries

United States; Austria; Colombia; Estonia; Guatemala; Iceland; India; Lithuania; Malaysia; Mexico; Philippines; Poland; Puerto Rico; Romania; South Africa; South Korea; Spain; Sweden

References

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.

Reference Type: DERIVED

PMID: 28327140 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28241822 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28197834 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27977934 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27600862 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26580237 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26579834 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26373629 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26121561 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25813214 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25329038 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24918789 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24786834 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24742013 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24585202 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24517339 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24073995 (View on PubMed)

Other Identifiers

28431754DIA3005

Identifier Type: OTHER

Identifier Source: secondary_id

CR017011

Identifier Type: -

Identifier Source: org_study_id