Characterization of the Kinetics of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus (T2DM)

Characterization of the Kinetics of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

It is anticipated that 7 days of oral administration of 10 mg dapagliflozin will reduce the renal glucose reabsorption similarly in healthy subjects and in subjects with T2DM.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria for T2DM

• Diagnosis of T2DM
• Must be on one of the following therapies: diet therapy alone, diet plus a sulfonylurea, diet plus metformin, or diet plus sulfonylurea plus metformin
• Subjects taking metformin, and/or sulfonylurea must be on a stable dose for at least 2 months prior to study drug administration
• Must have a fasting plasma glucose concentration ≤ 200 mg/dl, and HbA1C ≤ 10%

Inclusion criteria for healthy subjects:

• Healthy subjects (as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations)

Inclusion criteria for all subjects:

• Subjects with (eGFR ≥ 60 and ≤ 160 mL/min/1.73m² and urinary albumin excretion < 300 mg/g creatinine)
• Body Mass Index (BMI) of 18 to 38 kg/m²
• Men and women, ages 18 to 65 years, inclusive

Exclusion criteria for all subjects:

• Subjects with Type 1 Diabetes or uncontrolled Type 2 Diabetes Mellitus
• Subjects with T2DM with fasting plasma glucose > 200 mg/dL, healthy subjects with fasting plasma glucose > 105 mg/dL
• Subjects with T2DM with HbA1C > 10.0%, healthy subjects with HbA1C > 6.8%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dapagliflozin (T2DM)	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Once daily, 7 days
Active Comparator: Dapagliflozin (Healthy Subjects)	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Once daily, 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The reduction in TmG after 7 days of oral administration of 10 mg of dapagliflozin	Before 7 days of oral administration of 10 mg of dapagliflozin
The reduction in TmG after 7 days of oral administration of 10 mg of dapagliflozin	After 7 days of oral administration of 10 mg of dapagliflozin

Secondary Outcome Measures

Outcome Measure	Time Frame
Splay of the glucose titration curve	Before 7 days of oral administration of 10 mg of dapagliflozin
Splay of the glucose titration curve	After 7 days of oral administration of 10 mg of dapagliflozin
Pharmacokinetics (Cmin, Cmax, Tmax, and AUC (TAU)) of dapagliflozin	Study Day 7
Pharmacokinetics (Cmin, Cmax, Tmax, and AUC (TAU)) of dapagliflozin	Study Day 8

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• MB102-066_CSR_synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: July 16, 2010
• First Posted (Estimate): July 19, 2010

Study Record Updates

• Last Update Posted (Estimate): November 17, 2016
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• 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; Dapagliflozin
• Other Study ID Numbers: MB102-066