Study to evaluate safety and efficacy of Dapagliflozin and Saxagliptin in patients with type 2 diabetes mellitus aged 10 to below 18 years old.
- Conditions
- Diabetes Mellitus Type 2MedDRA version: 21.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2015-005042-66-GB
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 243
1.Signed Written Informed Consent
a)Subjects (or designee) must be willing and able to give signed and dated written informed consent. Minor’s parent(s) or legally acceptable representatives must give fully informed written consent. Assent should be obtained according to local regulations and if child is capable.
2.Target Population
a)Previously diagnosed with T2DM by World Health Organization/ADA criteria
b)HbA1c = 6.5% and = 10.5% obtained during the 6-month screening period.
c)Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to Day 1 randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject’s therapeutic regimen had been previously made but had not been successful.
d)Subject re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated).
i)If re-enrolled, the subject must be re-consented. All screening procedures will be repeated. Subjects may only be re-screened twice.
3.Age and Reproductive Status
a)Male and female patients eligible if reached 10 years of age at screening, and up to but not including 18 years of age at randomization. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects.
b)Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin) within 24 hours prior to the start of study drug.
c)Women must not be breastfeeding.
d)Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion.
Are the trial subjects under 18? yes
Number of subjects for this age range: 243
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Target Disease Exceptions
a)Presence of Type 1 diabetes, as demonstrated by:
•Preexisting diagnosis of Type 1 diabetes,
OR
•Positivity at screening of either antibodies to glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase like protein antibodies (IA-2) AND abnormally low levels of C-peptide. GAD and IA-2 antibody testing will be performed in all screened subjects, C-peptide only in otherwise eligible, antibody-positive subjects. All instances of antibody positive subjects with normal or elevated C-peptide values will be discussed by the Investigator with the study medical monitors and Sponsor’s study director to confirm study eligibility.
b)Previous diagnosis of monogenic etiology of Type 2 diabetes such as maturity onset diabetes of the young (MODY), genetic disorders with strong associations with insulin resistance/diabetes and/or obesity such as Turner’s Syndrome and Prader-Willi, or secondary diabetes (steroid use, Cushing’s disease, acromegaly), secondary diabetes mellitus, or diabetes insipidus
c)Diabetes ketoacidosis (DKA) within 6 months of screening
d)Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
i)Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
ii)Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), SGLT-2 inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)
e)Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study.
2. Medical History and Concurrent Diseases
a)Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
b)History of unstable or rapidly progressive renal disease
c)History of unresolved vesico-ureteral reflux
d)History of or current, acute or chronic pancreatitis
e)History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
f)Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
g)Significant co-morbidity that, in the opinion of the Investigators, will increase the risk to the subject such as immunosuppression, or current treatment for cancer
h)Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to the Day 1 visit
NOTE: inhaled, nasal spray, or topical steroids if limited to minor surface area are allowed.
3. Physical and Laboratory Test Findings
a)Abnormal renal function, which is defined as an estimated glomerular filtration rate (eGFR) calculated by the Schwartz Formula < 80 mL/min/1.73 m2 (1.33 mL/s)16
b)An abnormal thyroid-stimulating hormone (TSH) value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded.
c)Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
d)Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of normal (ULN), or clinically significant hepa
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method