Clinical trial NCT00554450: Renal Impairment in Type 2 Diabetic Subjects
Official title: The Pharmacodynamics, Pharmacokinetics, and Safety of Dapagliflozin in Type 2 Diabetic Subjects With Mild, Moderate, and Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-11-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the effect of dapagliflozin on renal glucose clearance in type 2 diabetic subjects with mild, moderate, and severe renal impairment compared to type 2 diabetic and healthy subjects with normal renal function


Eligibility criteria: Key Inclusion Criteria:

* Subjects in the following groups:

Group A: Healthy Subjects with Normal Renal Function (CLcr \> 80 mL/min) Group B: Diabetic Subjects with Normal Renal Function (CLcr \> 80 mL/min) Group C: Diabetic Subjects with Mild Renal Impairment (CLcr \> 50 - ≤80 mL/min) Group D: Diabetic Subjects with Moderate Renal Impairment (CLcr ≥ 30 - ≤50 mL/min) Group E: Diabetic Subjects with Severe Renal Impairment (CLcr \< 30 mL/min) (and not receiving dialysis)

* Men and WOCBP, ages 18 to 79 years old

Standard Exclusion Criteria, plus:

* History of diabetic ketoacidosis
* HbA\*1c \> 10%
* Serum albumin \< 2.0 gm/dL
* Potassium \< 3.0 or \> 6.0 mEq/L

Primary outcomes:
measure: Urine will be collected over a 24 h period for determination of renal glucose clearance, total protein, and measurement of total glucose excreted in urine
timeFrame: on Days -1, 1, 4 and 10
measure: Blood samples for serum glucose and creatinine will be collected
timeFrame: on Days -1, 1, 4 and 10 at selected timepoints
measure: Blood and urine PK samples
timeFrame: on Days 1, 4, 10
measure: Iohexol PK blood & urine samples for GFR assessment
timeFrame: on Day -12 to -5
Secondary outcomes:
measure: AEs, vital signs
timeFrame: scr, Days -1, 1, 4-11, discharge
measure: physical exams
timeFrame: scr, Days -12 to -5, -1, discharge
measure: ECGs
timeFrame: scr, Days,-1, 4, 7, discharge
measure: clinical labs
timeFrame: scr, Day -1, 1, 4, 6, 8, 10, discharge
measure: The following urine/serum safety parameters will be assessed: sodium, potassium, magnesium, phosphorus, calcium, and total protein (urine only)
timeFrame: on Days -1, 1, 4 and 10
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: St. Paul
country: United States
facility: Prism Research
state: Minnesota
city: San Antonio
country: United States
facility: Dgd Research, Inc.
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kasichayanula S, Liu X, Pe Benito M, Yao M, Pfister M, LaCreta FP, Humphreys WG, Boulton DW. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol. 2013 Sep;76(3):432-44. doi: 10.1111/bcp.12056.