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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01809327
First received: March 8, 2013
Last updated: August 22, 2014
Last verified: August 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.


Enrollment: 1186
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 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
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: NCT01809327

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
United States, California
Encinitas, California, United States
Newport Beach, California, United States
Northridge, California, United States
Norwalk, California, United States
Rancho Cucamonga, California, United States
Walnut Creek, California, United States
United States, Colorado
Denver, Colorado, United States
Northglenn, Colorado, United States
United States, Florida
Hialeah, Florida, United States
Miami, Florida, United States
New Port Richey, Florida, United States
Opa Locka, Florida, United States
United States, Georgia
Perry, Georgia, United States
United States, Indiana
Evansville, Indiana, United States
United States, Louisiana
Mandeville, Louisiana, United States
Metairie, Louisiana, United States
Sunset, Louisiana, United States
United States, Michigan
Flint, Michigan, United States
Kalamazoo, Michigan, United States
Royal Oak, Michigan, United States
Troy, Michigan, United States
United States, Mississippi
Olive Branch, Mississippi, United States
Picayune, Mississippi, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
West Seneca, New York, United States
United States, North Carolina
Hickory, North Carolina, United States
Mooresville, North Carolina, United States
United States, Ohio
Franklin, Ohio, United States
Mason, Ohio, United States
Perrysburg, Ohio, United States
Zanesville, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
Yukon, Oklahoma, United States
United States, Oregon
Tualatin, Oregon, United States
United States, Pennsylvania
Fleetwood, Pennsylvania, United States
Norristown, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
United States, South Dakota
Rapid City, South Dakota, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Austin, Texas, United States
Bellaire, Texas, United States
Dallas, Texas, United States
Houston, Texas, United States
Pearland, Texas, United States
Plano, Texas, United States
United States, Utah
Bountiful, Utah, United States
Salt Lake City, Utah, United States
United States, Virginia
Danville, Virginia, United States
Norfolk, Virginia, United States
Richmond, Virginia, United States
Argentina
Buenos Aires, Argentina
Caba, Argentina
Cordoba, Argentina
Mar Del Plata, Argentina
Moron, Argentina
Rosario, Argentina
Zarate, Argentina
Brazil
Passo Fundo, Brazil
Sao Paulo, Brazil
São Paulo, Brazil
Czech Republic
Kromeriz, Czech Republic
Pardubice, Czech Republic
Praha, Czech Republic
Praha 8, Czech Republic
Unicov, Czech Republic
Hungary
Balatonfured, Hungary
Budapest, Hungary
Eger, Hungary
Szikszó, Hungary
Zalaegerszeg, Hungary
Korea, Republic of
Goyang-Si, Korea, Republic of
Seoul, Korea, Republic of
Suwon, Korea, Republic of
Mexico
Aguascalientes, Mexico
Celaya, Mexico
Durango, Mexico
Guadalajara, Mexico
Mexico, Mexico
Monterrey, Mexico
Pachuca De Soto, Mexico
Tampico, Mexico
Puerto Rico
Carolina, Puerto Rico
Ponce, Puerto Rico
San Juan, Puerto Rico
Trujillo Alto, Puerto Rico
Romania
Bacau, Romania
Brasov, Romania
Bucharest, Romania
Bucuresti, Romania
Oradea, Romania
Tg Mures, Romania
Russian Federation
Arkhangelsk, Russian Federation
Barnaul, Russian Federation
Chelyabinsk, Russian Federation
Kemerovo, Russian Federation
Moscow, Russian Federation
Penza, Russian Federation
Rostov-On-Don, Russian Federation
Saint Petersburg, Russian Federation
Saint-Petersburg, Russian Federation
Samara, Russian Federation
Saratov, Russian Federation
Smolensk, Russian Federation
St Petersburg, Russian Federation
St-Petersburg, Russian Federation
Syktyvkar, Russian Federation
Tomsk, Russian Federation
Tyumen, Russian Federation
Voronezh, Russian Federation
Slovakia
Banska Bystrica, Slovakia
Bratislava, Slovakia
Malacky, Slovakia
Presov, Slovakia
Rimavska Sobota, Slovakia
Sahy, Slovakia
Trebisov, Slovakia
South Africa
Cape Town, South Africa
Durban, South Africa
Halfway, South Africa
Johannesburg, South Africa
Johannesburg N/A, South Africa
Soweto, Johannesburg, South Africa
Worcester, South Africa
Turkey
Ankara, Turkey
Antalya, Turkey
Canakkale, Turkey
Denizli, Turkey
Gaziantep, Turkey
Isparta, Turkey
Kahramanmaras, Turkey
Kayseri, Turkey
Malatya, Turkey
Samsun, Turkey
Ukraine
Cherkasy, Ukraine
Dnepropetrovsk, Ukraine
Donetsk, Ukraine
Ivano Frankivsk, Ukraine
Kharkov, Ukraine
Kiev, Ukraine
Kyiv, Ukraine
Lviv, Ukraine
Odesa, Ukraine
Poltava, Ukraine
Sumy, Ukraine
Zaporozhye, Ukraine
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More 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: August 22, 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 September 30, 2014