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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: Canagliflozin 300mg/Placebo
* Drug: Canagliflozin 300mg/Canagliflozin 150mg
* Drug: Canagliflozin 300mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 001<br>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<br>* Treatment A: Form=capsule, route=oral administration. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods.<br>|
| Experimental: 002<br>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<br>* 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.<br>|
| Experimental: 003<br>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<br>* 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.<br>|
| Experimental: 004<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin, Placebo, Type 2 diabetes mellitus