An Efficacy, Safety, and Tolerability Study of Canagliflozin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy - Full Text View

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 receiving treatment with metformin monotherapy (ie, treatment with a single drug) and have inadequate glycemic (blood sugar) control.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Canagliflozin 50 mg Drug: Placebo Drug: Canagliflozin 150 mg Drug: Metformin	Phase 2

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, 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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Canagliflozin

U.S. FDA Resources

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

Primary Outcome Measures:

Change in hemoglobin A1c from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Percentage of patients with adverse events as a measure of safety and tolerability [ Time Frame: Up to week 18 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in fasting plasma glucose from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Percentage of patients with hemoglobin A1c <7% (last observation carried forward) [ Time Frame: Week 18 ] [ Designated as safety issue: No ]
Percentage of patients with hemoglobin A1c <6.5% (last observation carried forward) [ Time Frame: Week 18 ] [ Designated as safety issue: No ]
Change in body mass index (BMI) from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in body weight from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in systolic blood pressure from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in diastolic blood pressure from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in high-density lipoprotein cholesterol (HDL-C) from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in triglycerides from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in total cholesterol from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]
Change in the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) from baseline to week 18 (last observation carried forward) [ Time Frame: Day 1 (Baseline) and Week 18 ] [ Designated as safety issue: No ]

Enrollment:	279
Study Start Date:	July 2011
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Canagliflozin 50 mg bid Each patient will receive 50 mg canagliflozin twice daily for 18 weeks.	Drug: Canagliflozin 50 mg One canagliflozin 50-mg capsule taken orally twice daily with a meal for 18 weeks Drug: Metformin The patient's stable daily dose of Metformin background therapy should be continued throughout the study.
Experimental: Canagliflozin 150 mg bid Each patient will receive 150 mg canagliflozin twice daily for 18 weeks	Drug: Canagliflozin 150 mg 1 canagliflozin 150-mg capsule taken orally twice daily with a meal for 18 weeks Drug: Metformin The patient's stable daily dose of Metformin background therapy should be continued throughout the study.
Placebo Comparator: Placebo Each patient will receive matching placebo twice daily for 18 weeks	Drug: Placebo 1 placebo capsule taken orally twice daily with a meal for 18 weeks Drug: Metformin The patient's stable daily dose of Metformin background therapy should be continued throughout the study.

Detailed Description:

This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study doctor will know the identity of assigned study drug), placebo-controlled, parallel-group,3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin compared to placebo (a capsule that is identical in appearance to canagliflozin but does not contain active drug) in patients with type 2 diabetes mellitus (T2DM) who are not achieving an adequate response from current antihyperglycemic therapy with metformin to control their diabetes. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with T2DM. Patients will take single-blind placebo capsules orally (by mouth) for 2 weeks before randomization. Patients will be randomly assigned canagliflozin or matching placebo, orally, twice daily, with 1 capsule taken with the morning meal and 1 capsule taken with the evening meal (2 capsules per day) and concurrent with metformin, if applicable, for up to 18 weeks. The dosing time of metformin should remain the same throughout the study.

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 metformin
Patients in the study must have a HbA1c between >=7 and <=10.5%
Patients must have 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, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01340664

Show 66 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:	NCT01340664 History of Changes
Other Study ID Numbers:	CR017914, 28431754DIA2003, 2010-024256-28
Study First Received:	April 21, 2011
Last Updated:	March 1, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:

Canagliflozin
Placebo
Metformin
Hemoglobin A1c
Type 2 diabetes mellitus

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 May 21, 2013