A Randomized, Double-Blind, Placebo-controlled, Single-center Phase 1 Pilot Study to Explore the Safety and Pharmacokinetics of a Single-Dose of DAPAglifozin as Add-on to Intravenous Insulin-Infusion in Adolescent and Adult Subjects with Type 1 Diabetes mellitus

Active, not recruiting

Conditions: Type 1 Diabetes mellitus
Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Registration Number: EUCTR2014-003552-31-DE

Lead Sponsor: Kinderkrankenhaus AUF DER BULT

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

For inclusion in the study subjects should fulfill the following criteria:
1.Provision of informed consent from participant and all legal representatives prior to any study specific procedures
2.Female and/or male aged 12 to 21years (both inclusive)
3.Subject must have type 1 diabetes (as diagnosed clinically) = 12 months
4.without completely inadequate glycemic control, defined as local laboratory A1c above 12.5% (subjects will be stratified according to glycemic control being in target (A1c 5.5 to 7.4%), slightly elevated (7.5 – 9.0%) or clearly elevated 9.1 – 12.5% ) obtained at the screening visit (Note: A one-time central laboratory re-test of the A1C is allowed)
5.Insulin use with an average daily dose between 0.6 – 2.0 U/kg, either continuous subcutaneous insulin infusion, (CSII) or multiple doses (at least 2x/day) of insulin
6.BMI 18.0 to 35.0 kg/m2 for adults or BMI between 10th and 99th age and gender related centile for pediatric patients
7.Minimum weight of 50 kg
8.Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator
9.WOCBP must have a negative urine pregnancy test at screening as well as at Visit 2 and Visit 4.
10.Women must not be breastfeeding

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Target Disease Exclusions
a) History of T2DM, maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
b) Any use of oral hypoglycemic agents within 12 months prior to the screening visit
c) History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit
d) History of diabetes insipidus
e) History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia)
within 3 months prior to prior to the screening visit
f) Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy, or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit. An unexplained event is defined as an event that cannot be explained by circumstances such as dietary (e.g. missed meal), strenuous exercise, error in insulin dosing, etc.
g) Hypoglycemic unawareness
h) History of Addison’s disease or chronic adrenal insufficiency

2) Physical and Laboratory Test Findings
a)Aspartate aminotransferase (AST) > 2X Upper limit of normal (ULN)
b)Alanine aminotransferase (ALT) > 2X ULN
c)Serum total bilirubin > 2X ULN
d)Estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula = 60 ml/min/1.73m2. e)Hemoglobin = 11.0 g/dl (110 g/l) for boys / men; hemoglobin =10.0 g/dl (100 g/L) for girls / women.
f)Creatine kinase (CK) > 3X ULN
g)Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody.
h)Abnormal Free T4
3) Allergies and Adverse Drug Reaction
a) Allergies or contraindication to the contents of dapagliflozin tablets or insulin

4) Renal, Hepatic, Hemotological/Oncological Diseases/Conditions
a)History of unstable or rapidly progressing renal disease
b)Conditions of congenital renal glucosuria
c)Renal allograft
d)Significant hepatic disease, including but not limited to, chronic active hepatitis and/or severe hepatic insufficiency
e)Documented history of hepatotoxicity with any medication
f)Documented history of severe hepatobiliary disease
g)History of hemoglobinopathy, with the exception of sickle cell trait (SA) or thalassemia minor; or chronic or recurrent hemolysis
h)Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 6 weeks prior to the enrolment visit
i)Known immunocompromised status, including but not limited to, individuals who have undergone organ transplantation or who are positive for the human immunodeficiency virus
j)Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma of the skin)

5) Other Exclusion Criteria
a)Prisoners or subjects who are involuntarily incarcerated
b)Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
c)Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to Day -3 visit. NOTE: Topical or inhaled corticosteroids are allowed.
d)Any unstable endocrine, psychiatric, rheumatic disorders as judged by the Investigator.
e)Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may aff