BMS - Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Dapagliflozin in Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 2 Trial to Explore the Safety, Pharmacokinetics and Pharmacodynamics of Dapagliflozin as an Add-on to Insulin Therapy in Subjects With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01498185
• Other study ID #: MB102-072
• Status: Completed
• Phase: Phase 2
• First received: December 21, 2011
• Last updated: March 20, 2015
• Start date: February 2012
• Est. completion date: October 2012

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To obtain safety and tolerability information in patients with type 1 diabetes where Dapagliflozin is added on to Insulin (for 14 days)

Description:

Study Classification : Safety, Pharmacokinetics and Pharmacodynamics

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes with central lab Glycosylated hemoglobin (A1C) = 7.0% and = 10.0%

• Insulin use for at least 12 months and initiation immediately after diagnosis of diabetes

• Method of Insulin administration [multiple daily injections (MDI) or continuous subcutaneous Insulin infusion (CSII)] stable = 3 months

• Stable basal Insulin dose = 2 weeks

• Ages 18 to 65 years

• Central laboratory C-peptide value of < 0.7 ng/mL

• Body mass index (BMI) 18.5 to 35.0 kg/m2

Exclusion Criteria:

• History of type 2 diabetes mellitus (T2DM), maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis

• Oral hypoglycemic agents

• History of diabetes ketoacidosis (DKA) within 24 weeks

• History of hospital admission for glycemic control within 6 months

• Frequent episodes of hypoglycemia (2 unexplained within 3 months) or hypoglycemic unawareness

• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) or Serum total bilirubin > 2X Upper limit of normal (ULN)

• Abnormal Free T4 [if screening Thyroid Stimulating Hormone (TSH) abnormal]

• Estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) formula = 60 mL/min/1.73m2

• Cardiovascular (CV)/Vascular Diseases within 6 months

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin
Tablets, Oral, 1 mg, Once daily, 14 days
• Placebo matching Dapagliflozin
Tablets, Oral, 0 mg, Once daily, 14 days

Locations

Country	Name	City	State
United States	Profil Institute For Clinical Research, Inc.	Chula Vista	California
United States	Dallas Diabetes & Endocrine Center	Dallas	Texas
United States	Jasper Clinic, Inc.	Kalamazoo	Michigan
United States	Kansas City University Of Medicine And Biosciences	Kansas City	Missouri
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	Louisiana Research Associates, Inc.	New Orleans	Louisiana
United States	Compass Research Phase 1, Llc	Orlando	Florida
United States	Vince And Associates Clinical Research	Overland Park	Kansas
United States	Progressive Medical Research	Port Orange	Florida
United States	Regional Medical Clinic-Endocrinology	Rapid City	South Dakota
United States	Va San Diego Healthcare System	San Diego	California
United States	La Biomed Research Inst. At Harbor Ucla Med Ctr.	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of Dapagliflozin as measured by numbers of subjects with SAEs, deaths or discontinuations due to AEs, events of hypoglycemia, AEs of genitourinary infection or potentially clinically significant changes in vital signs	SAEs = Serious adverse events, AEs = Adverse events	14 days	Yes
Primary	Number of subjects with potentially clinically significant changes in vital signs (defined as marked abnormality)		14 days	Yes
Secondary	Change from baseline to day 7 in mean glucose based on 7-point central laboratory glucose		Baseline (Day -1) and 7 days	No
Secondary	Maximum observed plasma concentration (Cmax) of Dapagliflozin and its major inactive metabolite		7 days	No
Secondary	Time of maximum observed plasma concentration (Tmax) of Dapagliflozin and its major inactive metabolite		7 days	No
Secondary	Area under the concentration-time curve in one dosing interval [AUC(TAU)] of Dapagliflozin and its major inactive metabolite		7 days	No
Secondary	Ratio of metabolite to parent area under the curve [AUC] (corrected for molecular weight) of Dapagliflozin and its major inactive metabolite		7 days	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form
•   MB102072_Clinical_Study_Protocol