Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus Aged 10 to Below 18 Years Old

• Register: ClinicalTrials.gov
• Last refreshed on: 4 December 2023
• Main ID: NCT03199053
• Date of registration: 22/06/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus Aged 10 to Below 18 Years Old
• Scientific title: A 26 Week, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Phase 3 Trial With a 26 Week Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 5 and 10 mg, and Saxagliptin 2.5 and 5 mg in Pediatric Patients With Type 2 Diabetes Mellitus Who Are Between 10 and Below 18 Years of Age
• Date of first enrolment: October 11, 2017
• Target sample size: 256
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03199053
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Finland, India, Israel, Italy, Korea, Republic of, Malaysia, Mexico, New Zealand, Philippines, Poland, Romania, Russian Federation, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Signed Written Informed Consent

- Target Population

- Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA
criteria

- HbA1c between 6.5% and 10.5% obtained at screening.

- 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 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.

- Age and Reproductive Status

- Male and female patients eligible if 10 years of age, up to but not including 18 years
of age at the time of enrollment/screening. 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.

- Women of childbearing potential must have a negative pregnancy test within 24 hours
prior to the start of study drug.

- Women must not be breastfeeding.

- 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.

Exclusion Criteria:

- Target Disease Exceptions

- Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1
diabetes,

- Previous diagnosis of monogenic etiology of Type 2 diabetes

- Diabetes ketoacidosis (DKA) within 6 months of screening

- Current use of the following medications for the treatment of diabetes, or use within
the specified timeframe prior to screening for the main study:

- Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or
injectable incretins or incretin mimetics, other antidiabetes medications not
otherwise specified.

- Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication
related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2)
inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)

- 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.

- Medical History and Concurrent Diseases

- Pregnant, positive serum pregnancy test, planning to become pregnant during the
clinical trials, or breastfeeding

- History of unstable or rapidly progressive renal disease

- History of unresolved vesico-ureteral reflux

- History of or current, acute or chronic pancreatitis

- History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia
minor; or chronic or recurrent hemolysis

- Malignancy within 5 years of the screening visit (with the exception of treated basal
cell or treated squamous cell carcinoma)

- 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

- Physical and Laboratory Test Findings

- Abnormal renal function,

- 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.

- Hematuria (confirmed by microscopy at screening) with no explanation as judged by the
Investigator up to randomization.

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of
normal (ULN), or clinically significant hepatic disease.

- Serum total bilirubin (TB) > 2x ULN unless exclusively caused by Gilbert's syndrome

- Positive serologic evidence of current infectious liver disease including anti
hepatitis A virus (HAV) (IgM), hepatitis B surface antigen (HBsAg), or anti hepatitis
C virus (HCV). Patients who have isolated positive anti-hepatitis B surface antibodies
may be included.

- Anemia of any etiology

- Volume-depleted subjects.

- Allergies and Adverse Drug Reaction

- Known allergy, sensitivity or contraindication to any study drug or its
excipient/vehicle

- Other Exclusion Criteria

- Subject is currently abusing alcohol or other drugs or has done so within the last 6
months prior to the screening visit.

- Prisoners or subjects who are involuntarily incarcerated. (Note: under certain
specific circumstances a person who has been imprisoned may be included or permitted
to continue as a subject. Strict conditions apply and Sponsor/designee approval is
required.)

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness.

- Psychiatric or cognitive disorder that will, in the opinion of investigators, limit
the subject's ability to comply with the study medications and monitoring.

- Subjects who have contraindications to therapy as outlined in the saxagliptin and
dapagliflozin Investigator Brochure or local package inserts.

- Participation and receiving IP in another clinical study during the prior 3 months



Age minimum: 10 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2

Intervention(s)

Drug: Dapagliflozin

Drug: Placebo

Drug: Saxagliptin

Primary Outcome(s)

Change from baseline in HbA1c at Week 26 [Time Frame: 26 weeks]

Secondary Outcome(s)

Percentage of subjects with baseline HbA1c = 7%, who achieve an HbA1c level < 7.0% at Week 26 [Time Frame: 26 weeks]

Change from baseline in Fasting Plasma Glucose at Week 26 [Time Frame: 26 weeks]

Secondary ID(s)

2015-005042-66

D1680C00019

Source(s) of Monetary Support

Please refer to primary and secondary sponsors