A Efficacy, Safety, and Tolerability Study of Canagliflozin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Alone or in Combination With a Sulphonylurea

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, 18-Week 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 Alone or in Combination With a Sulphonylurea

The purpose of this study is to assess the safety, tolerability, and efficacy of the addition of canagliflozin relative to the addition of placebo in patients with inadequate glycemic control on metformin alone or in combination with a sulphonylurea.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Canagliflozin 100mg; Drug: Metformin; Drug: Sulphonylurea; Drug: Canagliflozin 300mg; Drug: Placebo

Detailed Description

This is a double-blind (neither study staff or the patient will know the identity of the treatment assigned) study of canagliflozin where Chinese and other Asian adult patients with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic control on metformin alone or in combination with a sulphonylurea (SU) will be randomized (assigned to 1 of 3 treatments by chance) to receive the addition of treatment with canagliflozin 100 mg once daily, canagliflozin 300 mg once daily, or matching placebo capsules (placebo is a treatment identical in appearance to canagliflozin but does not contain active drug). All patients will take orally (by mouth) 1 single-blind placebo capsule once daily before the first meal of the day for up to 2 weeks (last dose of single-blind placebo to be taken the day before the baseline (Day 1) visit. On Day 1, patients will take orally, once daily 1 capsule of canagliflozin 100 mg, canagliflozin 300 mg, or placebo before the first meal of the day for up to 18 weeks.

• Study Type: Interventional
• Enrollment (Actual): 678
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China
  • Beijing, China
  • Changchun, China
  • Changsha, China
  • Chengdu, China
  • Chongqing, China
  • Guangzhou, China
  • Hangzhou, China
  • Harbin, China
  • Nanchang, China
  • Nanjing, China
  • Nanning, China
  • Shanghai, China
  • Shenyang, China
  • Shiyan, China
  • Siping, China
  • Su Zhou, China
  • Tianjin, China
  • Wuxi, China
  • Xi'An, China
• Malaysia
  • Kota Bharu, Malaysia
  • Pulau Pinang, Malaysia
  • Selangor, Malaysia
• Vietnam
  • Hanoi, Vietnam
  • Ho Chi Minh, Vietnam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with T2DM with inadequate glycemic control on metformin monotherapy or on metformin in combination with an SU at protocol-specified doses and having HbA1c >=7.0% and <=10.5% at Week -2 are eligible for enrollment in the study.

Exclusion Criteria:

• History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
• Has repeated (ie, 2 or more over a 1-week period) fasting plasma glucose (FPG) and/or fasting self-monitored blood glucose (SMBG) measurements >=270 mg/dL (15 mmol/L) during the pre-treatment phase, despite reinforcement of diet and exercise counseling
• History of a severe hypoglycemic episode within 6 months before screening
• History of or current illness considered to be clinically significant by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canagliflozin 100mg; Each participant will receive 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Canagliflozin 100mg; Type=1, unit=mg, number=100, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).; Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.
Experimental: Canagliflozin 300mg; Each participant will receive 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.; Drug: Canagliflozin 300mg; Type=1, unit=mg, number=300, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).
Placebo Comparator: Placebo; Each participant will receive matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.; Drug: Placebo; Form=capsule, route=oral administration. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18	The table below shows the least-squares (LS) mean change in HbA1c from baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.	Day 1 (Baseline) and Week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18	The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.	Day 1 (Baseline) and Week 18
Percent Change in Body Weight From Baseline to Week 18	The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.	Day 1 (Baseline) and Week 18
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18	The table below shows the percentage of patients with HbA1c <7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.	Day 1 (Baseline) and Week 18
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18	The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.	Day 1 (Baseline) and Week 18

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): May 9, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Canagliflozin; Placebo
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Canagliflozin
• Other Study ID Numbers: CR018541; 28431754DIA3014 (Other Identifier: Janssen Research & Development, LLC)