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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: November 7, 2014
Last verified: November 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

  Show 146 Study Locations
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: November 7, 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
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014