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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01809327
• Other study ID #: CR100034
• Secondary ID: 28431754DIA30112
• Status: Completed
• Phase: Phase 3
• First received: March 8, 2013
• Last updated: January 14, 2016
• Start date: June 2013
• Est. completion date: December 2014

Study information

• Verified date: January 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationHungary: National Institute for Quality and Organizational Development in Healthcare and MedicinesUkraine: State Pharmacological Center - Ministry of HealthUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1186
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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).
• 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).
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Czech Republic,  Hungary,  Korea, Republic of,  Mexico,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26	The change in the value of glycated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) from baseline at Week 26 was compared between the different treatment groups.	Day 1 (Baseline) and Week 26	No
Secondary	Percent Change in Body Weight From Baseline to Week 26	The percentage change in body weight from baseline to Week 26 was compared between the different treatment groups.	Day 1 (Baseline) and Week 26	No
Secondary	Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26	The percentage of participants achieved HbAIc less than 7 percent at Week 26 was compared between the different treatment groups.	Week 26	No
Secondary	Change in Systolic Blood Pressure From Baseline at Week 26	The change in systolic blood pressure from baseline at Week 26 was compared between the different treatment groups.	Day 1 (Baseline) and Week 26	No
Secondary	Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26	The percentage change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) from baseline to Week 26 was compared between the different treatment groups.	Day 1 (Baseline) and Week 26	No
Secondary	Percent Change in Triglycerides From Baseline to Week 26	The percentage change in triglycerides from baseline to Week 26 was compared between the different treatment groups.	Day 1 (Baseline) and Week 26	No
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.	Up to 30 weeks of last study drug administration	Yes