Clinical Trials List
Protocol NumberCV181375/ AZ study number: D1680C00019
NCT Number(ClinicalTrials.gov Identfier)NCT03199053
2017-12-08 - 2023-02-01
Phase III
Recruiting2
Suspended1
ICD-10E11
Type 2 diabetes mellitus
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
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
AstraZeneca
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林怡君 無
- Yu-Tzu Chang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 楊佳鳳 無
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
Co-Principal Investigator
- 張尹凡 無
- 潘妤玟 無
- Chih-Jen Chang 無
- Horng-Yih Ou 無
- Yen-Yin Chou 無
- Jin-Shang Wu 無
- 蔡孟哲 無
- Hao-Chang Hung 無
The Actual Total Number of Participants Enrolled
0 Suspended
Audit
None
Condition/Disease
Type 2 Diabetes Mellitus in Pediatric Patients
Objectives
Primary Objective
To determine if there will be a greater mean reduction from baseline in HbA1c achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c < 7% at 12 weeks) compared to placebo in pediatric T2DM subjects with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.
Test Drug
Dapagliflozin / Saxagliptin
Active Ingredient
Dapagliflozin
Saxagliptin
Saxagliptin
Dosage Form
Tablet
Dosage
5 mg, 10 mg
2.5 mg, 5 mg
2.5 mg, 5 mg
Endpoints
Primary Outcome Measures:
1. Change from baseline in HbA1c at Week 26.
Secondary Outcome Measures:
1. Change from baseline in Fasting Plasma Glucose at Week 26.
2. Percentage of subjects with baseline HbA1c ≥ 7%, who achieve an HbA1c level < 7.0% at Week 26.
Other Outcome Measures:
1. Percentage of subjects who require glycemic rescue medication or discontinue the study medication due to lack of efficacy during the 26-week treatment period.
2. Change from baseline in HbA1c at Week 52.
3. Change from baseline in FPG at Week 52.
4. Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% at Week 52.
1. Change from baseline in HbA1c at Week 26.
Secondary Outcome Measures:
1. Change from baseline in Fasting Plasma Glucose at Week 26.
2. Percentage of subjects with baseline HbA1c ≥ 7%, who achieve an HbA1c level < 7.0% at Week 26.
Other Outcome Measures:
1. Percentage of subjects who require glycemic rescue medication or discontinue the study medication due to lack of efficacy during the 26-week treatment period.
2. Change from baseline in HbA1c at Week 52.
3. Change from baseline in FPG at Week 52.
4. Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% at Week 52.
Inclution Criteria
1. Signed Written Informed Consent.
2. Target Population.
3. Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria.
4. HbA1c between 6.5% and 10.5% obtained at screening.
5. 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.
6. Age and Reproductive Status.
7. 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.
8. Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
9. Women must not be breastfeeding.
10. 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.
2. Target Population.
3. Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria.
4. HbA1c between 6.5% and 10.5% obtained at screening.
5. 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.
6. Age and Reproductive Status.
7. 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.
8. Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
9. Women must not be breastfeeding.
10. 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
1. Target Disease Exceptions
2. Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
3. Previous diagnosis of monogenic etiology of Type 2 diabetes
4. Diabetes ketoacidosis (DKA) within 6 months of screening
5. Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
6. Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
7. 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)
8. 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.
9. Medical History and Concurrent Diseases
10. Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
11. History of unstable or rapidly progressive renal disease
12. History of unresolved vesico-ureteral reflux
13. History of or current, acute or chronic pancreatitis
14. History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
15. Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
16. 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
17. Physical and Laboratory Test Findings
18. Abnormal renal function,
19. 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.
20. Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
21. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of normal (ULN), or clinically significant hepatic disease.
22. Serum total bilirubin (TB) > 2x ULN unless exclusively caused by Gilbert's syndrome
23. 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.
24. Anemia of any etiology
25. Volume-depleted subjects.
26. Allergies and Adverse Drug Reaction
27. Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
28. Other Exclusion Criteria
29. Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
30. 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.)
31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
32. Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.
33. Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
34. Participation and receiving IP in another clinical study during the prior 3 months
2. Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
3. Previous diagnosis of monogenic etiology of Type 2 diabetes
4. Diabetes ketoacidosis (DKA) within 6 months of screening
5. Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
6. Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
7. 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)
8. 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.
9. Medical History and Concurrent Diseases
10. Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
11. History of unstable or rapidly progressive renal disease
12. History of unresolved vesico-ureteral reflux
13. History of or current, acute or chronic pancreatitis
14. History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
15. Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
16. 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
17. Physical and Laboratory Test Findings
18. Abnormal renal function,
19. 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.
20. Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
21. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of normal (ULN), or clinically significant hepatic disease.
22. Serum total bilirubin (TB) > 2x ULN unless exclusively caused by Gilbert's syndrome
23. 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.
24. Anemia of any etiology
25. Volume-depleted subjects.
26. Allergies and Adverse Drug Reaction
27. Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
28. Other Exclusion Criteria
29. Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
30. 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.)
31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
32. Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.
33. Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
34. Participation and receiving IP in another clinical study during the prior 3 months
The Estimated Number of Participants
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Taiwan
8 participants
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Global
243 participants
