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 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
2 other identifiers
interventional
256
23 countries
122
Brief 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 diet and exercise and metformin, insulin, or metformin plus insulin.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 diabetes-mellitus-type-2
Started Oct 2017
Longer than P75 for phase_3 diabetes-mellitus-type-2
122 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2017
CompletedFirst Posted
Study publicly available on registry
June 26, 2017
CompletedStudy Start
First participant enrolled
October 11, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 3, 2024
CompletedResults Posted
Study results publicly available
April 17, 2024
CompletedJune 21, 2024
May 1, 2024
5.3 years
June 22, 2017
January 31, 2024
May 28, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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.
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
Baseline and Week 26
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Baseline and Week 26
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Baseline and Week 26
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Baseline and Week 26
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Baseline and Week 26
- +12 more secondary outcomes
Study Arms (5)
Low dose Dapagliflozin
EXPERIMENTALOral 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
EXPERIMENTALOral 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
EXPERIMENTALOral 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
EXPERIMENTALOral 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 COMPARATOROral route. Placebo tablets administered for 52 weeks
Interventions
Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily
Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily
Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (122)
Research Site
Sacramento, California, 95821, United States
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New Haven, Connecticut, 06519, United States
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Hialeah, Florida, 33012, United States
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Hialeah, Florida, 33016, United States
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Hollywood, Florida, 33021, United States
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Miami, Florida, 33144, United States
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Miami, Florida, 33155, United States
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Miami, Florida, 33165, United States
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Miami Springs, Florida, 33166, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30341, United States
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Idaho Falls, Idaho, 83404, United States
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Neptune City, New Jersey, 07753, United States
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Memphis, Tennessee, 38116, United States
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Memphis, Tennessee, 38119, United States
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Edinburg, Texas, 78539, United States
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Harlingen, Texas, 78550, United States
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McAllen, Texas, 78503, United States
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San Antonio, Texas, 78229, United States
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Charlottesville, Virginia, 22903, United States
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Buenos Aires, 6500, Argentina
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Buenos Aires, C1180AAX, Argentina
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CABA, C1119ACN, Argentina
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Ciudad de Buenos Aires, C1405BCH, Argentina
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San Miguel de Tucumán, 4000, Argentina
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San Miguel de Tucumán, T4000IHE, Argentina
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Blacktown, 2148, Australia
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Brasília, 71625-009, Brazil
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Curitiba, 80810-040, Brazil
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Fortaleza, 60170-320, Brazil
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Fortaleza, 60430-270, Brazil
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Passo Fundo, 99010-080, Brazil
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Porto Alegre, 90430-001, Brazil
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Porto Alegre, 91350-250, Brazil
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Ribeirão Preto, 14051-104, Brazil
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Santa Maria, 97015-530, Brazil
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São Paulo, 01223-001, Brazil
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São Paulo, 05652-900, Brazil
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Montreal, Quebec, H1T 2M4, Canada
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Santiago, 7500710, Chile
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Armenia, 630004, Colombia
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Barranquilla, 80020, Colombia
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Tampere, 33520, Finland
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Ahmedabad, 380008, India
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Aurangabad, 431003, India
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Bangalore, 560002, India
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Bikaner, 334003, India
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Chandigarh, 160012, India
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Coimbatore, 641009, India
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Hyderabad, 500012, India
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Kolkata, 700054, India
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Kozhikode, 67300, India
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Nashik, 422002, India
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Pune, 411030, India
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Visakhapatnam, 531011, India
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Haifa, 3109601, Israel
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Ancona, 60123, Italy
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Napoli, 80138, Italy
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Roma, 00165, Italy
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George Town, 10450, Malaysia
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Ipoh, 30990, Malaysia
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Johor Bahru, 80100, Malaysia
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Klang, 41200, Malaysia
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Kota Kinabalu, 88996, Malaysia
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Kuala Lumpur, 50586, Malaysia
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Kuching, 93586, Malaysia
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Malacca, 75400, Malaysia
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Putrajaya, 62250, Malaysia
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Seremban, 70300, Malaysia
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Seri Manjung, 32040, Malaysia
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Taiping, 34000, Malaysia
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Boca del Rio, 94290, Mexico
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Celaya, 38000, Mexico
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Ciudad Madero, 89440, Mexico
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Cuernavaca, 62209, Mexico
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Cuernavaca, 62290, Mexico
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Culiacán, 80230, Mexico
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Durango, 34000, Mexico
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Guadalajara, 44150, Mexico
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Juriquilla, 76230, Mexico
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Mérida, 97000, Mexico
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México, 06700, Mexico
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México, D.F., 11410, Mexico
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Monterrey, 64460, Mexico
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Monterrey, 64620, Mexico
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San Juan del Río, 76800, Mexico
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Veracruz, 91900, Mexico
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Zapopan, 45116, Mexico
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Grafton, 1023, New Zealand
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Tauranga, 3110, New Zealand
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Wellington, 6021, New Zealand
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Quezon City, 1100, Philippines
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Quezon City, 1112, Philippines
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San Fernando City, 2000, Philippines
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Warsaw, 01-868, Poland
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Izhevsk, 426009, Russia
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Moscow, 125993, Russia
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Ufa, 450000, Russia
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Daejeon, 35233, South Korea
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Incheon, 22332, South Korea
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Wŏnju, 26426, South Korea
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Tainan, 704, Taiwan
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Taipei, 112, Taiwan
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Bangkok, 10400, Thailand
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Hat Yai, 90110, Thailand
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Aydin, 9010, Turkey (Türkiye)
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Bursa, 16059, Turkey (Türkiye)
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Eskişehir, 26480, Turkey (Türkiye)
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Istanbul, 34020, Turkey (Türkiye)
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Izmir, 35210, Turkey (Türkiye)
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Izmir, 35330, Turkey (Türkiye)
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Kocaeli, 41380, Turkey (Türkiye)
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Kurupelit, 55139, Turkey (Türkiye)
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Manisa, 45030, Turkey (Türkiye)
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Dnipro, 49023, Ukraine
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Kyiv, 01021, Ukraine
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Vinnytsia, 21010, Ukraine
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Birmingham, B4 6NH, United Kingdom
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London, E1 1BB, United Kingdom
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London, SE5 9RS, United Kingdom
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Middlesbrough, TS4 3BW, United Kingdom
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Nottingham, NG7 2UH, United Kingdom
Related Publications (1)
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.
PMID: 38320500DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Due to legal dispute, the source documents could not be accessed for 11 participants at 1 site. All data from this site were excluded as documented in the statistical analysis plan.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- sponsor
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2017
First Posted
June 26, 2017
Study Start
October 11, 2017
Primary Completion
February 1, 2023
Study Completion
January 3, 2024
Last Updated
June 21, 2024
Results First Posted
April 17, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 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.
- Access Criteria
- 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.
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.