Clinical trial NCT01273558: A Study of Two Methods for Determining the Renal Threshold for Glucose in Patients With Type 2 Diabetes Mellitus
Official title: An Open-Label Study to Compare Two Methods for Determining the Renal Threshold for Glucose in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Canagliflozin
Renal threshold for glucose
Pharmacodynamics
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2011-01-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: RTG values using the MMTT and the stepwise hyperglycemic clamp methods
timeFrame: On Days 1 and 2 (Part 1)
measure: RTG values using the MMTT and the stepwise hyperglycemic clamp methods
timeFrame: On Days 7 and 8 (Part 2)
Secondary outcomes:
measure: Plasma glucose (PG) concentration during the MMT and the hyperglycemic clamp procedure
timeFrame: On Days 1 and 2 (Part 1)
measure: Plasma glucose (PG) concentration during the MMT and the hyperglycemic clamp procedure
timeFrame: On Days 7 and 8 (Part 2)
measure: Rate of Urinary glucose excretion (UGE) during the MMTT and the hyperglycemic clamp procedure
timeFrame: On Days 1 and 2 (Part 1)
measure: Rate of Urinary glucose excretion (UGE) during the MMTT and the hyperglycemic clamp procedure
timeFrame: On Days 7 and 8 (Part 2)
Other outcomes:
Locations:
city: Neuss
country: Germany
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Polidori D, Sha S, Ghosh A, Plum-Morschel L, Heise T, Rothenberg P. Validation of a novel method for determining the renal threshold for glucose excretion in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013 May;98(5):E867-71. doi: 10.1210/jc.2012-4205. Epub 2013 Apr 12.