Clinical trial NCT01498185: BMS - Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Dapagliflozin in Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Astra Zeneca, Bristol-Myers Squibb
First posted: 2011-12-23
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: Study Classification : Safety, Pharmacokinetics and Pharmacodynamics

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in 7-Point Glucose Monitoring (7-PGM) at Day 7
timeFrame: From Baseline to Day 7
Secondary outcomes:
measure: Dapagliflozin Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Dapagliflozin Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Dapagliflozin Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
timeFrame: Day 7 (0 hr to 24 hr post dose)
measure: Pharmacokinetic Parameters on Day 7 - Ratio of Metabolite (RM) to Parent AUC[TAU]
timeFrame: Day 7 (0 hr to 24 hr post dose)
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute For Clinical Research, Inc.
state: California
city: San Diego
country: United States
facility: Va San Diego Healthcare System
state: California
city: Torrance
country: United States
facility: La Biomed Research Inst. At Harbor Ucla Med Ctr.
state: California
city: Orlando
country: United States
facility: Compass Research Phase 1, Llc
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Overland Park
country: United States
facility: Vince And Associates Clinical Research
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana Research Associates, Inc.
state: Louisiana
city: Kalamazoo
country: United States
facility: Jasper Clinic, Inc.
state: Michigan
city: Kansas City
country: United States
facility: Kansas City University Of Medicine And Biosciences
state: Missouri
city: Rapid City
country: United States
facility: Regional Medical Clinic-Endocrinology
state: South Dakota
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Melin J, Tang W, Rekic D, Hamren B, Penland RC, Boulton DW, Parkinson J. Dapagliflozin Pharmacokinetics Is Similar in Adults With Type 1 and Type 2 Diabetes Mellitus. J Clin Pharmacol. 2022 Oct;62(10):1227-1235. doi: 10.1002/jcph.2062. Epub 2022 May 2.
citation: Henry RR, Rosenstock J, Edelman S, Mudaliar S, Chalamandaris AG, Kasichayanula S, Bogle A, Iqbal N, List J, Griffen SC. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015 Mar;38(3):412-9. doi: 10.2337/dc13-2955. Epub 2014 Sep 30.