A Study to Evaluate the Effect of JNJ-28431754 (Canagliflozin) on Post-Meal Glucose in Patients With Type 2 Diabetes Mellitus

A Double-Blind, Placebo-Controlled, Randomized, Crossover, Multicenter Study to Evaluate the Effect of JNJ-28431754 (Canagliflozin) on Post-Meal Glucose in Subjects With Type 2 Diabetes Mellitus

The purpose of this study is to evaluate the effect of canagliflozin on post-meal glucose blood levels in patients with Type 2 Diabetes Mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Canagliflozin 300mg/Placebo; Drug: Canagliflozin 300mg; Drug: Canagliflozin 300mg/Canagliflozin 150mg

Detailed Description

This is a double-blind (neither study staff or the patient will know the identity of the treatment assigned) study of canagliflozin in patients with Type 2 Diabetes Mellitus (T2DM) who are currently taking metformin at a stable dose of >=1500 mg/day. Patients will participate in the study for up to approximately 16 weeks. During the study, patients will receive 4 treatments (A, B, C, and D); each treatment will be administered during a 3-day treatment period. Patients will receive 1 dose of study medication in the morning of Day 1 and Day 2 of each treatment period and treatment periods will be separated by approximately 2 weeks. Treatments will consist of placebo (A), canagliflozin 300 mg and placebo (B), canagliflozin 300mg (C), and canagliflozin 300mg and canagliflozin 150mg (D).

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States
  • Florida
    • Miramar, Florida, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Texas
    • Dallas, Texas, United States
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with T2DM with inadequate glycemic control (based upon fasting glucose measurements >=130 mg/dL and <=250 mg/dL) on metformin monotherapy or on metformin in dual combination with other glucose lowering agents (sulphonylurea [SU] or a meglitinide or a dipeptidyl peptidase-4 [DPP-4] inhibitor) 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
• history of a severe hypoglycemic episode within 6 months before screening
• Has repeated (ie, 2 or more over a 1-week period) fasting plasma glucose (FPG) and/or fasting self-monitored blood glucose (SMBG) measurements >=250 mg/dL (13.88 mmol/L) during the pre-treatment phase, despite reinforcement of diet and exercise counseling
• 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: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 001; Placebo Treatment A: Form=capsule route=oral administration. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods.	Drug: Placebo; Treatment A: Form=capsule, route=oral administration. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods.
Experimental: 002; Canagliflozin 300mg/Placebo Treatment B: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Form=capsule route=oral administration. Capsule is taken once on Day 2 in 1 of 4 treatment periods.	Drug: Canagliflozin 300mg/Placebo; Treatment B: Type=1, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Form=capsule, route=oral administration. Capsule is taken once on Day 2 in 1 of 4 treatment periods.
Experimental: 003; Canagliflozin 300mg Treatment C: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods.	Drug: Canagliflozin 300mg; Treatment C: Type=1, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods.
Experimental: 004; Canagliflozin 300mg/Canagliflozin 150mg Treatment D: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Type=1 unit=mg number=150 form=capsule route=oral use. Capsule is taken once on Day 2 in 1 of 4 treatment periods.	Drug: Canagliflozin 300mg/Canagliflozin 150mg; Treatment D: Type=1, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Type=1, unit=mg, number=150, form=capsule, route=oral use. Capsule is taken once on Day 2 in 1 of 4 treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of glucose	Up to Day 44

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of insulin secretion	Up to Day 44
Urinary glucose excretion (UGE)	Up to Day 44
Renal threshold of glucose excretion (RTG)	Up to Day 44
Adverse events	Up to approximately Day 44

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

General Publications

• Stein P, Berg JK, Morrow L, Polidori D, Artis E, Rusch S, Vaccaro N, Devineni D. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism. 2014 Oct;63(10):1296-303. doi: 10.1016/j.metabol.2014.07.003. Epub 2014 Jul 9.

Helpful Links

• A Double-Blind, Placebo-Controlled, Randomized, Crossover, Multicenter Study to Evaluate the Effect of JNJ-28431754 (canagliflozin) on Post-Meal Glucose in Subjects With Type 2 Diabetes Mellitus

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: April 19, 2013
• Last Verified: April 1, 2013

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; Canagliflozin
• Other Study ID Numbers: CR018373; 28431754DIA1045