Diabetes Mellitus, Type 2Phase 3NCT03199053
Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus (T2DM) Aged 10 to Below 18 Years Old
A Phase 3 study testing Dapagliflozin and Saxagliptin in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 122 sites in 23 countries.
Trial summary
The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on… Read more about this study
- Who is it for?
- Ages 10 to 18 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Dapagliflozin and Saxagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 122 sitesin 23 countries
- Study dates
- 11 Oct 2017to 3 Jan 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
122 sites in 23 countries.
122 sites in 23 countries
United States20 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Atlanta, Georgia, 30341
Research Site
Charlottesville, Virginia, 22903
Research Site
Edinburg, Texas, 78539
Research Site
Harlingen, Texas, 78550
Research Site
Hialeah, Florida, 33012
Research Site
Hialeah, Florida, 33016
Research Site
Hollywood, Florida, 33021
Research Site
Idaho Falls, Idaho, 83404
Research Site
McAllen, Texas, 78503
Research Site
Memphis, Tennessee, 38116
Research Site
Memphis, Tennessee, 38119
Research Site
Miami, Florida, 33144
Research Site
Miami, Florida, 33155
Research Site
Miami, Florida, 33165
Research Site
Miami Springs, Florida, 33166
Research Site
Neptune City, New Jersey, 07753
Research Site
New Haven, Connecticut, 06519
Research Site
Sacramento, California, 95821
Research Site
San Antonio, Texas, 78229
Mexico17 sites
Research Site
Boca del Rio, 94290
Research Site
Celaya, 38000
Research Site
Ciudad Madero, 89440
Research Site
Cuernavaca, 62209
Research Site
Cuernavaca, 62290
Research Site
Culiacán, 80230
Research Site
Durango, 34000
Research Site
Guadalajara, 44150
Research Site
Juriquilla, 76230
Research Site
Mérida, 97000
Research Site
México, 06700
Research Site
México, D.F., 11410
Research Site
Monterrey, 64460
Research Site
Monterrey, 64620
Research Site
San Juan del Río, 76800
Research Site
Veracruz, 91900
Research Site
Zapopan, 45116
India12 sites
Research Site
Ahmedabad, 380008
Research Site
Bangalore, 560002
Research Site
Bikaner, 334003
Research Site
Chandigarh, 160012
Research Site
Chhatrapati Sambhajinagar, 431003
Research Site
Coimbatore, 641009
Research Site
Hyderabad, 500012
Research Site
Kolkata, 700054
Research Site
Kozhikode, 67300
Research Site
Nashik, 422002
Research Site
Pune, 411030
Research Site
Visakhapatnam, 531011
Malaysia12 sites
Research Site
George Town, 10450
Research Site
Ipoh, 30990
Research Site
Johor Bahru, 80100
Research Site
Klang, 41200
Research Site
Kota Kinabalu, 88996
Research Site
Kuala Lumpur, 50586
Research Site
Kuching, 93586
Research Site
Malacca, 75400
Research Site
Putrajaya, 62250
Research Site
Seremban, 70300
Research Site
Seri Manjung, 32040
Research Site
Taiping, 34000
Brazil11 sites
Research Site
Brasília, 71625-009
Research Site
Curitiba, 80810-040
Research Site
Fortaleza, 60170-320
Research Site
Fortaleza, 60430-270
Research Site
Passo Fundo, 99010-080
Research Site
Porto Alegre, 90430-001
Research Site
Porto Alegre, 91350-250
Research Site
Ribeirão Preto, 14051-104
Research Site
Santa Maria, 97015-530
Research Site
São Paulo, 01223-001
Research Site
São Paulo, 05652-900
Turkey (Türkiye)9 sites
Research Site
Aydin, 9010
Research Site
Bursa, 16059
Research Site
Eskişehir, 26480
Research Site
Istanbul, 34020
Research Site
Izmir, 35210
Research Site
Izmir, 35330
Research Site
Kocaeli, 41380
Research Site
Kurupelit, 55139
Research Site
Manisa, 45030
Argentina6 sites
Research Site
Buenos Aires, 6500
Research Site
Buenos Aires, C1180AAX
Research Site
CABA, C1119ACN
Research Site
Ciudad de Buenos Aires, C1405BCH
Research Site
San Miguel de Tucumán, 4000
Research Site
San Miguel de Tucumán, T4000IHE
United Kingdom5 sites
Research Site
Birmingham, B4 6NH
Research Site
London, E1 1BB
Research Site
London, SE5 9RS
Research Site
Middlesbrough, TS4 3BW
Research Site
Nottingham, NG7 2UH
Italy3 sites
Research Site
Ancona, 60123
Research Site
Naples, 80138
Research Site
Roma, 00165
New Zealand3 sites
Research Site
Grafton, 1023
Research Site
Tauranga, 3110
Research Site
Wellington, 6021
Philippines3 sites
Research Site
Quezon City, 1100
Research Site
Quezon City, 1112
Research Site
San Fernando City, 2000
Russia3 sites
Research Site
Izhevsk, 426009
Research Site
Moscow, 125993
Research Site
Ufa, 450000
South Korea3 sites
Research Site
Daejeon, 35233
Research Site
Incheon, 22332
Research Site
Wŏnju, 26426
Ukraine3 sites
Research Site
Dnipro, 49023
Research Site
Kyiv, 01021
Research Site
Vinnytsia, 21010
Colombia2 sites
Research Site
Armenia, 630004
Research Site
Barranquilla, 80020
About this study
Official 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
The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Dapagliflozin, Saxagliptin, Placebo
- Keywords
- Type 2 Diabetes Mellitus
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Forxiga
Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily
SaxagliptinDrug
Also called Onglyza
Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily
PlaceboDrug
Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily
| Study group | Role | What they receive |
|---|---|---|
| Low dose Dapagliflozin | Experimental | Oral route. Start with a low dose of dapagliflozin administered once daily and remain on the low dose regardless of your HbA1c at week 12. Receives: Drug: Dapagliflozin |
| Low dose/high dose Dapagliflozin | Experimental | Oral route. Start with a low dose of Dapagliflozin administered once daily and up titrate to the high dose Dapagliflozin administered once daily if HbA1c >= 7% at week 12 Receives: Drug: Dapagliflozin |
| Low dose Saxagliptin | Experimental | Oral route. Start with a low dose of saxagliptin administered once daily and remain on the low dose regardless of your HbA1c at week 12 Receives: Drug: Saxagliptin |
| Low dose/high dose Saxagliptin | Experimental | Oral route. Start with a low dose of saxagliptin administered once daily and up titrate to the high dose if HbA1c >= 7% at week 12 Receives: Drug: Saxagliptin |
| Placebo arm | Placebo comparator | Oral route. Placebo tablets administered for 52 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on multiple imputation washout (MI-WO) within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Secondary outcomes (17)
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Dapagliflozin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Saxagliptin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Dapagliflozin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Saxagliptin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Dapagliflozin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Saxagliptin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Dapagliflozin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Saxagliptin participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
A logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Participants were weighted as follows: participants who had HbA1c < 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c >= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c >= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.
Measured: Baseline and Week 26
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
Measured: Baseline and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2017
- Study start11 Oct 2017
- Primary completion1 Feb 2023
- Study completion3 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized 1:1:1 to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Blinded HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c \< 7% will remain on previously assigned randomized treatment. Subjects taking dapagliflozin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (dapagliflozin 5 mg) or up titrate to the high-dose treatment (dapagliflozin 10 mg). Subjects taking saxagliptin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (saxagliptin 2.5 mg) or up-titrate to the high-dose treatment (saxagliptin 5 mg). Subjects taking placebo with Week 12 HbA1c ≥ 7% will continue on placebo treatment. All placebo subjects and all subjects taking saxagliptin or dapagliflozin with HbA1c \< 7% at Week 12 will go through a dummy 2nd randomization process for maintaining the blinding.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 256 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199053
- Sponsor's protocol ID
- D1680C00019
- Other IDs
- 2015-005042-66, 2015
- Status last verified
- May 2024
- First submitted
- 22 Jun 2017
- Last updated
- 21 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Shehadeh N, Barrett T, Galassetti P, Karlsson C, Monyak J, Iqbal N, Tamborlane WV. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. NEJM Evid. 2023 Dec;2(12):EVIDoa2300210. doi: 10.1056/EVIDoa2300210. Epub 2023 Oct 4.
PubMed 38320500
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03199053
- Acronym / sponsor ID
- D1680C00019
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Type 2 Diabetes Mellitus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 256 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 1 Feb 2023 (actual)
- Study completion
- 3 Jan 2024 (actual)
- First posted
- 26 Jun 2017 (actual)
- Results
- Posted 17 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
- Model description
- Eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized 1:1:1 to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Blinded HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c < 7% will remain on previously assigned randomized treatment. Subjects taking dapagliflozin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (dapagliflozin 5 mg) or up titrate to the high-dose treatment (dapagliflozin 10 mg). Subjects taking saxagliptin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (saxagliptin 2.5 mg) or up-titrate to the high-dose treatment (saxagliptin 5 mg). Subjects taking placebo with Week 12 HbA1c ≥ 7% will continue on placebo treatment. All placebo subjects and all subjects taking saxagliptin or dapagliflozin with HbA1c < 7% at Week 12 will go through a dummy 2nd randomization process for maintaining the blinding.
| Arm | Type | Receives |
|---|---|---|
| Low dose Dapagliflozin | Experimental | Drug: DapagliflozinOral route. Start with a low dose of dapagliflozin administered once daily and remain on the low dose regardless of your HbA1c at week 12. |
| Low dose/high dose Dapagliflozin | Experimental | Drug: DapagliflozinOral route. Start with a low dose of Dapagliflozin administered once daily and up titrate to the high dose Dapagliflozin administered once daily if HbA1c >= 7% at week 12 |
| Low dose Saxagliptin | Experimental | Drug: SaxagliptinOral route. Start with a low dose of saxagliptin administered once daily and remain on the low dose regardless of your HbA1c at week 12 |
| Low dose/high dose Saxagliptin | Experimental | Drug: SaxagliptinOral route. Start with a low dose of saxagliptin administered once daily and up titrate to the high dose if HbA1c >= 7% at week 12 |
| Placebo arm | Placebo comparator | Drug: PlaceboOral route. Placebo tablets administered for 52 weeks |
Who may qualify
- Ages
- 10 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (34 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DapagliflozinAlso: ForxigaTablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily | Drug | Low dose Dapagliflozin, Low dose/high dose Dapagliflozin |
| SaxagliptinAlso: OnglyzaTablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily | Drug | Low dose Saxagliptin, Low dose/high dose Saxagliptin |
| PlaceboMatching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily | Drug | Placebo arm |
Primary outcome
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on multiple imputation washout (MI-WO) within each arm using the data from placebo participants with Week 26 data.
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.
17 secondary outcomes
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Time frame: Baseline and Week 26
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Time frame: Baseline and Week 26
Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Time frame: Baseline and Week 26
Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Time frame: Baseline and Week 26
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26
Time frame: Baseline and Week 26
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26
Time frame: Baseline and Week 26
Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Time frame: Baseline and Week 26
Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Time frame: Baseline and Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38320500Shehadeh N, Barrett T, Galassetti P, Karlsson C, Monyak J, Iqbal N, Tamborlane WV. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. NEJM Evid. 2023 Dec;2(12):EVIDoa2300210. doi: 10.1056/EVIDoa2300210. Epub 2023 Oct 4.
- CSR Synopsis\_RedactedLink provided by the sponsor.
- SAP\_RedactedLink provided by the sponsor.
- CSP\_RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
122 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dapagliflozin and Saxagliptin in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 122 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 122 sites in United States, Mexico, India, Malaysia, Brazil and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 (time frame: Baseline and Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03199053, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2024.