A Study to Evaluate the Effectiveness, Safety, and Tolerability of Canagliflozin in Combination With Metformin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise

This study is currently recruiting participants.
Verified April 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01809327
First received: March 8, 2013
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to assess the effectiveness of the co-administration of canagliflozin and metformin extended release (XR) compared with canagliflozin alone, and metformin XR alone in patients with type 2 diabetes mellitus with inadequate control despite treatment with diet and exercise. The safety and tolerability of canagliflozin will also be assessed.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Metformin XR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, 5-Arm, Parallel-Group, 26-Week, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in Combination With Metformin as Initial Combination Therapy in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in glycated hemoglobin (HbA1c) from baseline to Week 26 [ Time Frame: Day 1 (Baseline) up to Week 26 ] [ Designated as safety issue: No ]
    The change in HbA1c will be compared between the different treatment groups.


Secondary Outcome Measures:
  • Percent change in body weight from baseline to Week 26 [ Time Frame: Day 1 (Baseline) up to Week 26 ] [ Designated as safety issue: No ]
    The percent change in body weight will be compared between the different treatment groups.

  • Percentage of participants with glycated hemoglobin (HbAIc) less than 7 percent at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    The percentage of participants with HbAIc less than 7 percent will be compared between the different treatment groups.

  • Change in systolic blood pressure from baseline to Week 26 [ Time Frame: Day 1 (Baseline) up to Week 26 ] [ Designated as safety issue: No ]
    The change in systolic blood pressure will be compared between the different treatment groups.

  • Change in high-density lipoprotein cholesterol (HDL-C) from baseline to Week 26 [ Time Frame: Day 1 (Baseline) up to Week 26 ] [ Designated as safety issue: No ]
    The change in HDL-C will be compared between the different treatment groups.

  • Change in triglycerides from baseline to Week 26 [ Time Frame: Day 1 (Baseline) up to Week 26 ] [ Designated as safety issue: No ]
    The change in triglycerides will be compared between the different treatment groups.

  • Number of participants with adverse events [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events will be used as a measure of safety and tolerability.


Estimated Enrollment: 1200
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin 100 mg
Participants will receive one 100 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Drug: Canagliflozin 100 mg
One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).
Experimental: Canagliflozin 300 mg
Participants will receive one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Drug: Canagliflozin 300 mg
One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).
Experimental: Metformin XR
Participants will receive metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.
Drug: Metformin XR
One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.
Experimental: Canagliflozin 100 mg + Metformin XR
Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
Drug: Canagliflozin 100 mg
One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).
Drug: Metformin XR
One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.
Experimental: Canagliflozin 300 mg + Metformin XR
Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
Drug: Canagliflozin 300 mg
One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).
Drug: Metformin XR
One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.

Detailed Description:

This study will be a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), active-controlled (one of the treatments is an established effective treatment for type 2 diabetes mellitus), parallel-group (each group of participants will be treated at the same time), 5-arm (groups), multicenter study. Approximately 1,200 participants will be randomly assigned to the 5 treatment arms in a 1:1:1:1:1 ratio for 26 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have type 2 diabetes mellitus with inadequate glycemic control on diet and exercise
  • Not on antihyperglycemic agent therapy (at least 12 weeks before screening) and have a screening visit fingerstick glycated hemoglobin (HbA1c) of more than or equal to 7 percent and less than or equal to 12.5 percent
  • Have a screening visit HbA1c of more than or equal to 7.5 percent and less than or equal to 12 percent as determined by the central laboratory
  • Must have a fasting plasma glucose of less than or equal to 300 mg/dL (16.7 mmol/L) prior to randomization
  • Must have a fasting fingerstick glucose of greater than 120 mg/dL (6.7 mmol/L) performed at home or at the study center prior to randomization

Exclusion Criteria:

  • History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
  • Fasting C-peptide less than 0.70 ng/mL (0.23 nmol/L) in participants for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation
  • Repeated (2 or more over a 1 week period) fasting self-monitored blood glucose measurements more than 300 mg/dL (16.7 mmol/L) prior to randomization, despite reinforcement of diet and exercise counseling
  • History of hereditary glucose-galactose malabsorption or primary renal glucosuria
  • Has history of, or currently active, illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01809327

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Hide Study Locations
Locations
United States, Alabama
Withdrawn
Anniston, Alabama, United States
Recruiting
Birmingham, Alabama, United States
United States, Arizona
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Mesa, Arizona, United States
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Phoenix, Arizona, United States
Completed
Phoenix, Arizona, United States
United States, California
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Concord, California, United States
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Encinitas, California, United States
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Greenbrae, California, United States
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Newport Beach, California, United States
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Northridge, California, United States
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Norwalk, California, United States
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Rancho Cucamonga, California, United States
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Spring Valley, California, United States
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Walnut Creek, California, United States
United States, Colorado
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Denver, Colorado, United States
Completed
Northglenn, Colorado, United States
United States, Connecticut
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Waterbury, Connecticut, United States
United States, Florida
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Bradenton, Florida, United States
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Brooksville, Florida, United States
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Hialeah, Florida, United States
Completed
Hialeah, Florida, United States
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Hialeah, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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New Port Richey, Florida, United States
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Opa Locka, Florida, United States
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Palm Harbor, Florida, United States
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St. Petersburg, Florida, United States
United States, Georgia
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Perry, Georgia, United States
United States, Idaho
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Eagle, Idaho, United States
United States, Illinois
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Springfield, Illinois, United States
United States, Indiana
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Evansville, Indiana, United States
United States, Louisiana
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Baton Rouge, Louisiana, United States
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Mandeville, Louisiana, United States
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Metairie, Louisiana, United States
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Sunset, Louisiana, United States
United States, Maine
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Auburn, Maine, United States
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Portland, Maine, United States
United States, Maryland
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Elkridge, Maryland, United States
United States, Massachusetts
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Brockton, Massachusetts, United States
United States, Michigan
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Bingham Farms, Michigan, United States
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Flint, Michigan, United States
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Kalamazoo, Michigan, United States
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Royal Oak, Michigan, United States
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Troy, Michigan, United States
United States, Mississippi
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Olive Branch, Mississippi, United States
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Picayune, Mississippi, United States
United States, New Mexico
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Albuquerque, New Mexico, United States
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Albuquerque, New Mexico, United States
United States, New York
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West Seneca, New York, United States
United States, North Carolina
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Hickory, North Carolina, United States
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Mooresville, North Carolina, United States
United States, Ohio
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Cincinnati, Ohio, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Franklin, Ohio, United States
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Mason, Ohio, United States
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Perrysburg, Ohio, United States
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Zanesville, Ohio, United States
United States, Oklahoma
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Oklahoma City, Oklahoma, United States
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Yukon, Oklahoma, United States
United States, Oregon
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Tualatin, Oregon, United States
United States, Pennsylvania
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Fleetwood, Pennsylvania, United States
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Jersey Shore, Pennsylvania, United States
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Norristown, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
United States, South Dakota
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Rapid City, South Dakota, United States
United States, Tennessee
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Nashville, Tennessee, United States
United States, Texas
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Austin, Texas, United States
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Bellaire, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Houston, Texas, United States
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Pearland, Texas, United States
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Plano, Texas, United States
United States, Utah
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Bountiful, Utah, United States
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Salt Lake City, Utah, United States
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Salt Lake City, Utah, United States
United States, Virginia
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Danville, Virginia, United States
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Norfolk, Virginia, United States
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Richmond, Virginia, United States
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Virginia Beach, Virginia, United States
Argentina
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Olive Branch, MS, Argentina
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Buenos Aires, Argentina
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Caba, Argentina
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Cordoba, Argentina
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Cordoba, Argentina
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Mar Del Plata, Argentina
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Mendoza, Argentina
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Moron, Argentina
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Rosario, Argentina
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Rosario, Argentina
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Zarate, Argentina
Brazil
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Belem, Brazil
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Belo Horizonte, Brazil
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Brasilia, Brazil
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Campinas, Brazil
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Curitiba, Brazil
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Fortaleza, Brazil
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Goiânia, Brazil
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Marília, Brazil
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Mogi Das Cruzes, Brazil
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Passo Fundo, Brazil
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Recife, Brazil
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Rio De Janeiro, Brazil
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Sao Paulo, Brazil
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Sao Paulo, Brazil
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São Paulo, Brazil
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São Paulo, Brazil
Czech Republic
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Holesov, Czech Republic
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Kromeriz, Czech Republic
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Pardubce, Czech Republic
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Pardubice, Czech Republic
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Praha, Czech Republic
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Praha 8, Czech Republic
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Unicov, Czech Republic
Hungary
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Balatonfured, Hungary
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Budapest, Hungary
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Eger, Hungary
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Gyõr, Hungary
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Szentes, Hungary
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Szikszó, Hungary
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Zalaegerszeg, Hungary
Korea, Republic of
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Goyang-Si, Korea, Republic of
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Seoul, Korea, Republic of
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Suwon, Korea, Republic of
Mexico
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Aguascalientes, Mexico
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Celaya, Mexico
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Culiacan, Mexico
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Durango, Mexico
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Guadalajara, Mexico
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Mexico, Mexico
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Monterrey, Mexico
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Monterrey, Mexico
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Monterrey, Mexico
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Pachuca De Soto, Mexico
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Queretaro, Mexico
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Tampico, Mexico
Puerto Rico
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Carolina, Puerto Rico
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Ponce, Puerto Rico
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Ponce, Puerto Rico
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San Juan, Puerto Rico
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San Juan, Puerto Rico
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Trujillo Alto, Puerto Rico
Romania
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Bacau, Romania
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Brasov, Romania
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Bucharest, Romania
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Bucuresti, Romania
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Oradea, Romania
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Tg Mures, Romania
Russian Federation
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Arkhangelsk, Russian Federation
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Arkhangelsk, Russian Federation
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Barnaul, Russian Federation
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Barnaul, Russian Federation
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Chelyabinsk, Russian Federation
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Kemerovo, Russian Federation
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Kursk, Russian Federation
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Moscow, Russian Federation
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Moscow, Russian Federation
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Novosibirsk, Russian Federation
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Omsk, Russian Federation
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Penza, Russian Federation
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Perm, Russian Federation
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Rostov-On-Don, Russian Federation
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Saint Petersburg, Russian Federation
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Saint Petersburg, Russian Federation
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Saint-Petersburg, Russian Federation
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Samara, Russian Federation
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Saratov, Russian Federation
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Smolensk, Russian Federation
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St Petersburg, Russian Federation
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St Petersburg, Russian Federation
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St-Petersburg, Russian Federation
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Syktyvkar, Russian Federation
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Tomsk, Russian Federation
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Tyumen, Russian Federation
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Voronezh, Russian Federation
Slovakia
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Banska Bystrica, Slovakia
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Bratislava, Slovakia
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Malacky, Slovakia
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Presov, Slovakia
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Rimavska Sobota, Slovakia
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Sahy, Slovakia
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Trebisov, Slovakia
South Africa
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Cape Town, South Africa
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Durban, South Africa
Completed
Durban, South Africa
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Halfway, South Africa
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Johannesburg, South Africa
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Johannesburg N/A, South Africa
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Paarl, South Africa
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Soweto, Johannesburg, South Africa
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Worcester, South Africa
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Worcester, South Africa
Turkey
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Ankara, Turkey
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Antalya, Turkey
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Canakkale, Turkey
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Denizli, Turkey
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Gaziantep, Turkey
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Isparta, Turkey
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Kahramanmaras, Turkey
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Kayseri, Turkey
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Malatya, Turkey
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Samsun, Turkey
Ukraine
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Cherkasy, Ukraine
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Dnepropetrovsk, Ukraine
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Donetsk, Ukraine
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Ivano Frankivsk, Ukraine
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Kharkov, Ukraine
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Kiev, Ukraine
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Kyiv, Ukraine
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Lviv, Ukraine
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Odesa, Ukraine
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Poltava, Ukraine
Not yet recruiting
Simferopol, Ukraine
Recruiting
Sumy, Ukraine
Withdrawn
Vinnitsa, Ukraine
Recruiting
Zaporozhye, Ukraine
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01809327     History of Changes
Other Study ID Numbers: CR100034, 28431754DIA3011, 2011-000400-17
Study First Received: March 8, 2013
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Federal Government

Keywords provided by Janssen Research & Development, LLC:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Canagliflozin (JNJ-28431754)
Metformin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014