A Study of Two Methods for Determining the Renal Threshold for 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 compare the results from two methods used to determine the renal threshold for glucose excretion (defined as the lowest plasma glucose concentration at which appreciable amounts of glucose appear in the urine) in untreated patients with type 2 diabetes mellitus and in patients with type 2 diabetes mellitus who are treated with 100 mg once-daily canigliflozin for 8 days.

Detailed Description
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This is an open-label (patients will know if they are receiving treatment and the identity of the treatment) study that will compare renal threshold of glucose (RTG) values obtained by 2 different methods: an established method (ie, the stepwise hyperglycemic clamp method) and a new method (the mixed meal tolerance test [MMTT] method). The RTG is defined as the lowest plasma glucose concentration at which appreciable amounts of glucose appear in the urine. Each method for determining the RTG value will be performed in untreated patients with type 2 diabetes mellitus (T2DM) and in patients with T2DM who are treated with canagliflozin 100 mg once daily for 8 days. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with T2DM. Patients will not take study drug (canagliflozin 100 mg overencapsulated tablets) in Part 1 of the study. In Part 2 of the study, patients will take study drug once daily on Study Days 1 through 8.

Official Title
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An Open-Label Study to Compare Two Methods for Determining the Renal Threshold for Glucose in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM who are not receiving treatment with any anti-hyperglycemic agents (AHAs) for at least 12 weeks, or who are receiving treatment with a stable dose and regimen of metformin monotherapy for at least 12 weeks and have a hemoglobin A1c (HbA1c) in the range of >=7% to <=10% Exclusion Criteria: History of Type 1, brittle diabetes or secondary forms of diabetes History of 1 or more severe hypoglycemic episodes History of diabetic complications considered to be clinically significant by the Investigator History of or current illness considered to be clinically significant by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Part 1: no Intervention<br>In Part 1 of the study, patients will not receive any study drug. | |
| Experimental: Part 2: canagliflozin<br>In Part 2 of the study, patients will receive canagliflozin once daily on Days 1 through 8. | Drug: Canagliflozin<br>* One 100 mg capsule taken orally (by mouth) on Days Days 1-8<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RTG values using the MMTT and the stepwise hyperglycemic clamp methods |  | On Days 1 and 2 (Part 1) | 
| RTG values using the MMTT and the stepwise hyperglycemic clamp methods |  | On Days 7 and 8 (Part 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose (PG) concentration during the MMT and the hyperglycemic clamp procedure |  | On Days 1 and 2 (Part 1) | 
| Plasma glucose (PG) concentration during the MMT and the hyperglycemic clamp procedure |  | On Days 7 and 8 (Part 2) | 
| Rate of Urinary glucose excretion (UGE) during the MMTT and the hyperglycemic clamp procedure |  | On Days 1 and 2 (Part 1) | 
| Rate of Urinary glucose excretion (UGE) during the MMTT and the hyperglycemic clamp procedure |  | On Days 7 and 8 (Part 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin, Renal threshold for glucose, Pharmacodynamics