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

This study has been completed.
Sponsor:
Collaborator:
Astra Zeneca, Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01498185
First received: December 21, 2011
Last updated: December 20, 2016
Last verified: December 2016

December 21, 2011
December 20, 2016
February 2012
October 2012   (Final data collection date for primary outcome measure)
Mean Change From Baseline in 7-Point Glucose Monitoring (7-PGM) at Day 7 [ Time Frame: From Baseline to Day 7 ]
7-PGM was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the assessment on Day -1, prior to the start date and time of the first dose of the double-blind study medication. 7-PGM included the average of all available glucose values before and 2-hour (hr) after each meal (breakfast, lunch, dinner) as well as bedtime. Measurements were on Day -1, and Day 7 in the double-blind period.
  • 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 [ Time Frame: 14 days ]
    • SAEs - serious adverse events
    • AEs - adverse events
  • Number of subjects with potentially clinically significant changes in vital signs (defined as marked abnormality) [ Time Frame: 14 days ]
Complete list of historical versions of study NCT01498185 on ClinicalTrials.gov Archive Site
  • Dapagliflozin Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Cmax was recorded directly from experimental observations.
  • Dapagliflozin Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Tmax was recorded directly from experimental observations.
  • Dapagliflozin Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU]) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. AUC[TAU], was calculated by a mixture of logand linear-trapezoidal summations.
  • Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Cmax was recorded directly from experimental observations.
  • Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Tmax was recorded directly from experimental observations.
  • Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU]) [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. AUC[TAU], was calculated by a mixture of logand linear-trapezoidal summations.
  • Pharmacokinetic Parameters on Day 7 - Ratio of Metabolite (RM) to Parent AUC[TAU] [ Time Frame: Day 7 (0 hr to 24 hr post dose) ]
    Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. MR was calculated as the ratio of metabolite to parent AUC(TAU), corrected for molecular weights of dapagliflozin and dapagliflozin 3-O-glucuronide (408.82 and 584.99, respectively).
  • Change from baseline to day 7 in mean glucose based on 7-point central laboratory glucose [ Time Frame: Baseline (Day -1) and 7 days ]
  • Maximum observed plasma concentration (Cmax) of Dapagliflozin and its major inactive metabolite [ Time Frame: 7 days ]
  • Time of maximum observed plasma concentration (Tmax) of Dapagliflozin and its major inactive metabolite [ Time Frame: 7 days ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of Dapagliflozin and its major inactive metabolite [ Time Frame: 7 days ]
  • Ratio of metabolite to parent area under the curve [AUC] (corrected for molecular weight) of Dapagliflozin and its major inactive metabolite [ Time Frame: 7 days ]
Not Provided
Not Provided
 
BMS - Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Dapagliflozin in Type 1 Diabetes
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
To obtain safety and tolerability information in patients with type 1 diabetes where Dapagliflozin is added on to Insulin (for 14 days)
Study Classification : Safety, Pharmacokinetics and Pharmacodynamics
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
  • Drug: Dapagliflozin
    Tablets, Oral, 1 mg, Once daily, 14 days
  • Drug: Placebo matching Dapagliflozin
    Tablets, Oral, 0 mg, Once daily, 14 days
  • Experimental: Arm 1: Dapagliflozin (1 mg)
    Intervention: Drug: Dapagliflozin
  • Experimental: Arm 2: Dapagliflozin (2.5 mg)
    Intervention: Drug: Dapagliflozin
  • Experimental: Arm 3: Dapagliflozin (5 mg)
    Intervention: Drug: Dapagliflozin
  • Experimental: Arm 4: Dapagliflozin (10 mg)
    Intervention: Drug: Dapagliflozin
  • Experimental: Arm 5: Placebo matching Dapagliflozin
    Intervention: Drug: Placebo matching Dapagliflozin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
171
October 2012
October 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01498185
MB102-072
No
Not Provided
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Astra Zeneca, Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
AstraZeneca
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP