The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03199053




Registration number
NCT03199053
Ethics application status
Date submitted
22/06/2017
Date registered
26/06/2017

Titles & IDs
Public title
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
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
Secondary ID [1] 0 0
2015-005042-66
Secondary ID [2] 0 0
D1680C00019
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dapagliflozin
Treatment: Drugs - Saxagliptin
Treatment: Drugs - Placebo

Experimental: Low dose Dapagliflozin - 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.

Experimental: Low dose/high dose Dapagliflozin - 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

Experimental: Low dose Saxagliptin - 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

Experimental: Low dose/high dose Saxagliptin - 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

Placebo comparator: Placebo arm - Oral route. Placebo tablets administered for 52 weeks


Treatment: Drugs: Dapagliflozin
Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily

Treatment: Drugs: Saxagliptin
Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily

Treatment: Drugs: Placebo
Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [1] 0 0
Baseline and Week 26
Primary outcome [2] 0 0
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [2] 0 0
Baseline and Week 26
Secondary outcome [1] 0 0
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [1] 0 0
Baseline and Week 26
Secondary outcome [2] 0 0
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [2] 0 0
Baseline and Week 26
Secondary outcome [3] 0 0
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [3] 0 0
Baseline and Week 26
Secondary outcome [4] 0 0
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [4] 0 0
Baseline and Week 26
Secondary outcome [5] 0 0
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Timepoint [5] 0 0
Baseline and Week 26
Secondary outcome [6] 0 0
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [6] 0 0
Baseline and Week 26
Secondary outcome [7] 0 0
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [7] 0 0
Baseline and Week 26
Secondary outcome [8] 0 0
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [8] 0 0
Baseline and Week 26
Secondary outcome [9] 0 0
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [9] 0 0
Baseline and Week 26
Secondary outcome [10] 0 0
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [10] 0 0
Baseline and Week 26
Secondary outcome [11] 0 0
Percentage of Participants With Baseline HbA1c = 7% Who Achieved HbA1c < 7% at Week 26
Timepoint [11] 0 0
Baseline and Week 26
Secondary outcome [12] 0 0
Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c = 7% Who Achieved HbA1c < 7% at Week 26
Timepoint [12] 0 0
Baseline and Week 26
Secondary outcome [13] 0 0
Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c = 7% Who Achieved HbA1c < 7% at Week 26
Timepoint [13] 0 0
Baseline and Week 26
Secondary outcome [14] 0 0
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26
Timepoint [14] 0 0
Baseline and Week 26
Secondary outcome [15] 0 0
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26
Timepoint [15] 0 0
Baseline and Week 26
Secondary outcome [16] 0 0
Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c = 7% Who Achieved HbA1c < 7% at Week 26
Timepoint [16] 0 0
Baseline and Week 26
Secondary outcome [17] 0 0
Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c = 7% Who Achieved HbA1c < 7% at Week 26
Timepoint [17] 0 0
Baseline and Week 26

Eligibility
Key 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.
Minimum age
10 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Blacktown
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Caba
Country [12] 0 0
Argentina
State/province [12] 0 0
Ciudad de Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
San Miguel de Tucuman
Country [14] 0 0
Argentina
State/province [14] 0 0
San Miguel de Tucumán
Country [15] 0 0
Brazil
State/province [15] 0 0
Brasilia
Country [16] 0 0
Brazil
State/province [16] 0 0
Curitiba
Country [17] 0 0
Brazil
State/province [17] 0 0
Fortaleza
Country [18] 0 0
Brazil
State/province [18] 0 0
Passo Fundo
Country [19] 0 0
Brazil
State/province [19] 0 0
Porto Alegre
Country [20] 0 0
Brazil
State/province [20] 0 0
Ribeirão Preto
Country [21] 0 0
Brazil
State/province [21] 0 0
Santa Maria
Country [22] 0 0
Brazil
State/province [22] 0 0
Sao Paulo
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Chile
State/province [24] 0 0
Santiago
Country [25] 0 0
Colombia
State/province [25] 0 0
Armenia
Country [26] 0 0
Colombia
State/province [26] 0 0
Barranquilla
Country [27] 0 0
Finland
State/province [27] 0 0
Tampere
Country [28] 0 0
India
State/province [28] 0 0
Ahmedabad
Country [29] 0 0
India
State/province [29] 0 0
Aurangabad
Country [30] 0 0
India
State/province [30] 0 0
Bangalore
Country [31] 0 0
India
State/province [31] 0 0
Bikaner
Country [32] 0 0
India
State/province [32] 0 0
Chandigarh
Country [33] 0 0
India
State/province [33] 0 0
Coimbatore
Country [34] 0 0
India
State/province [34] 0 0
Hyderabad
Country [35] 0 0
India
State/province [35] 0 0
Kolkata
Country [36] 0 0
India
State/province [36] 0 0
Kozhikode
Country [37] 0 0
India
State/province [37] 0 0
Nashik
Country [38] 0 0
India
State/province [38] 0 0
Pune
Country [39] 0 0
India
State/province [39] 0 0
Visakhapatnam
Country [40] 0 0
Israel
State/province [40] 0 0
Haifa
Country [41] 0 0
Italy
State/province [41] 0 0
Ancona
Country [42] 0 0
Italy
State/province [42] 0 0
Napoli
Country [43] 0 0
Italy
State/province [43] 0 0
Roma
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Daejeon-si
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Incheon
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Wonju-si
Country [47] 0 0
Malaysia
State/province [47] 0 0
George Town
Country [48] 0 0
Malaysia
State/province [48] 0 0
Ipoh
Country [49] 0 0
Malaysia
State/province [49] 0 0
Johor Bahru
Country [50] 0 0
Malaysia
State/province [50] 0 0
Klang
Country [51] 0 0
Malaysia
State/province [51] 0 0
Kota Kinabalu
Country [52] 0 0
Malaysia
State/province [52] 0 0
Kuala Lumpur
Country [53] 0 0
Malaysia
State/province [53] 0 0
Kuching
Country [54] 0 0
Malaysia
State/province [54] 0 0
Melaka
Country [55] 0 0
Malaysia
State/province [55] 0 0
Putrajaya
Country [56] 0 0
Malaysia
State/province [56] 0 0
Seremban
Country [57] 0 0
Malaysia
State/province [57] 0 0
Seri Manjung
Country [58] 0 0
Malaysia
State/province [58] 0 0
Taiping
Country [59] 0 0
Mexico
State/province [59] 0 0
Boca del Rio
Country [60] 0 0
Mexico
State/province [60] 0 0
Celaya
Country [61] 0 0
Mexico
State/province [61] 0 0
Ciudad Madero
Country [62] 0 0
Mexico
State/province [62] 0 0
Cuernavaca
Country [63] 0 0
Mexico
State/province [63] 0 0
Culiacán
Country [64] 0 0
Mexico
State/province [64] 0 0
Durango
Country [65] 0 0
Mexico
State/province [65] 0 0
Guadalajara
Country [66] 0 0
Mexico
State/province [66] 0 0
Juriquilla
Country [67] 0 0
Mexico
State/province [67] 0 0
Merida
Country [68] 0 0
Mexico
State/province [68] 0 0
Mexico
Country [69] 0 0
Mexico
State/province [69] 0 0
Monterrey
Country [70] 0 0
Mexico
State/province [70] 0 0
México, D.F.
Country [71] 0 0
Mexico
State/province [71] 0 0
San Juan del Rio
Country [72] 0 0
Mexico
State/province [72] 0 0
Veracruz
Country [73] 0 0
Mexico
State/province [73] 0 0
Zapopan
Country [74] 0 0
New Zealand
State/province [74] 0 0
Grafton
Country [75] 0 0
New Zealand
State/province [75] 0 0
Tauranga
Country [76] 0 0
New Zealand
State/province [76] 0 0
Wellington
Country [77] 0 0
Philippines
State/province [77] 0 0
Quezon City
Country [78] 0 0
Philippines
State/province [78] 0 0
San Fernando City
Country [79] 0 0
Poland
State/province [79] 0 0
Warszawa
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Izhevsk
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moscow
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Ufa
Country [83] 0 0
Taiwan
State/province [83] 0 0
Tainan City
Country [84] 0 0
Taiwan
State/province [84] 0 0
Taipei
Country [85] 0 0
Thailand
State/province [85] 0 0
Bangkok
Country [86] 0 0
Thailand
State/province [86] 0 0
Hat Yai
Country [87] 0 0
Turkey
State/province [87] 0 0
Aydin
Country [88] 0 0
Turkey
State/province [88] 0 0
Bursa
Country [89] 0 0
Turkey
State/province [89] 0 0
Eskisehir
Country [90] 0 0
Turkey
State/province [90] 0 0
Istanbul
Country [91] 0 0
Turkey
State/province [91] 0 0
Izmir
Country [92] 0 0
Turkey
State/province [92] 0 0
Kocaeli
Country [93] 0 0
Turkey
State/province [93] 0 0
Kurupelit
Country [94] 0 0
Turkey
State/province [94] 0 0
Manisa
Country [95] 0 0
Ukraine
State/province [95] 0 0
Dnipro
Country [96] 0 0
Ukraine
State/province [96] 0 0
Kyiv
Country [97] 0 0
Ukraine
State/province [97] 0 0
Vinnytsia
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Birmingham
Country [99] 0 0
United Kingdom
State/province [99] 0 0
London
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Middlesborough
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.