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The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01106690
First received: April 1, 2010
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo
Drug: Canagliflozin
Drug: Sitagliptin
Drug: Metformin
Drug: Pioglitazone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Change in HbA1c From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.


Secondary Outcome Measures:
  • Percentage of Patients With HbA1c <7% at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    The table below shows the percentage of patients with HbA1c<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.

  • Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

  • Change in Homeostasis Model Assessment (HOMA2-%B) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    HOMA2-%B is a measure of beta cell function (the cells in the pancreas that produce and store insulin). The table below shows the least-squares (LS) mean change in HOMA2-%B from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

  • Percent Change in Body Weight From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

  • Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

  • Percent Change in Triglycerides From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

  • Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.


Enrollment: 344
Study Start Date: June 2010
Study Completion Date: July 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo/Sitagliptin
Each patient will receive matching placebo once daily for 26 weeks with stable doses of metformin and pioglitazone. At Week 26, patients will be switched from placebo to 100 mg of sitagliptin once daily with stable doses of metformin and pioglitazone until Week 52.
Drug: Placebo
One matching placebo capsule orally (by mouth) once daily for 26 weeks with stable doses of metformin and pioglitazone.
Drug: Sitagliptin
One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 with stable doses of metformin and pioglitazone.
Drug: Metformin
The patient's stable dose of metformin background therapy should be continued throughout the study.
Drug: Pioglitazone
The patient's stable dose of pioglitazone background therapy should be continued throughout the study.
Experimental: Canagliflozin 100 mg
Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with stable doses of metformin and pioglitazone.
Drug: Metformin
The patient's stable dose of metformin background therapy should be continued throughout the study.
Drug: Pioglitazone
The patient's stable dose of pioglitazone background therapy should be continued throughout the study.
Experimental: Canagliflozin 300 mg
Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with stable doses of metformin and pioglitazone.
Drug: Metformin
The patient's stable dose of metformin background therapy should be continued throughout the study.
Drug: Pioglitazone
The patient's stable dose of pioglitazone background therapy should be continued throughout the study.

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106690

  Hide Study Locations
Locations
United States, Alabama
Anniston, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
Tucson, Arizona, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Burlingame, California, United States
Encinitas, California, United States
Fullerton, California, United States
Roseville, California, United States
Santa Ana, California, United States
Wes Hills, California, United States
United States, Colorado
Colorado Springs, Colorado, United States
United States, Florida
Bartow, Florida, United States
Hollywood, Florida, United States
Jacksonville, Florida, United States
Pembroke Pines, Florida, United States
United States, Iowa
Des Moines, Iowa, United States
United States, Louisiana
Baton Rouge, Louisiana, United States
United States, Minnesota
Chaska, Minnesota, United States
United States, Mississippi
Picayune, Mississippi, United States
United States, Montana
Billings, Montana, United States
United States, North Carolina
Charlotte, North Carolina, United States
Hickory, North Carolina, United States
Raleigh, North Carolina, United States
United States, Ohio
Dublin, Ohio, United States
Perrysburg, Ohio, United States
United States, Oklahoma
Tulsa, Oklahoma, United States
Yukon, Oklahoma, United States
United States, Pennsylvania
Bensalem, Pennsylvania, United States
United States, Tennessee
Bristol, Tennessee, United States
Kingsport, Tennessee, United States
Nashville, Tennessee, United States
United States, Texas
Arlington, Texas, United States
Dallas, Texas, United States
Grand Prairie, Texas, United States
Houston, Texas, United States
New Braunfels, Texas, United States
San Antonio, Texas, United States
United States, Virginia
Falls Church, Virginia, United States
Virginia Beach, Virginia, United States
United States, Washington
Federal Way, Washington, United States
Selah, Washington, United States
Canada, New Brunswick
Bathurst, New Brunswick, Canada
Moncton, New Brunswick, Canada
Canada, Newfoundland and Labrador
Grand Falls-Windsor, Newfoundland and Labrador, Canada
Canada, Ontario
Brampton, Ontario, Canada
Hamilton, Ontario, Canada
Ottawa, Ontario, Canada
Smiths Falls, Ontario, Canada
Thornhill, Ontario, Canada
Canada, Quebec
Drummondville, Quebec, Canada
Canada
Calgary, Canada
Mount Pearl, Canada
Truro, Canada
Finland
Kuopio, Finland
Oulu, Finland
Turku, Finland
France
Bondy Cedex, France
Le Creusot, France
Narbonne Cedex, France
Germany
Aschaffenburg, Germany
Mainz, Germany
Neuwied, Germany
Schkeuditz, Germany
Greece
Athens, Greece
Thessaloniki, Greece
Thessalonikis, Greece
India
Ahmedabad, India
Belgaum, India
Chennai, India
Coimbatore, India
Jaipur, India
Nagpur, India
Mexico
Chihuahua, Mexico
Ciudad Juarez, Mexico
Durango, Mexico
Mexico, Mexico
Spain
Almería, Spain
Madrid, Spain
Sevilla, Spain
Thailand
Bangkok, Thailand
Khon Kaen, Thailand
United Kingdom
Antrim, United Kingdom
Belfast, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided by Janssen Research & Development, LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01106690     History of Changes
Other Study ID Numbers: CR017032, 28431754DIA3012
Study First Received: April 1, 2010
Results First Received: April 2, 2013
Last Updated: June 26, 2013
Health Authority: United States: Food and Drug Administration
Great Britain: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Janssen Research & Development, LLC:
Canagliflozin
Placebo
Sitagliptin (Januvia)
Metformin
Pioglitazone (Actos)
Hemoglobin A1c
Type 2 diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Pioglitazone
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014