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

• ClinicalTrials.gov Identifier: NCT03199053
• Recruitment Status: Recruiting
• First Posted: June 26, 2017
• Last Update Posted: December 10, 2020
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

The purpose of this research study is to evaluate the efficacy and safety of the drugs dapagliflozin and saxagliptin in patients with Type 2 Diabetes who are aged 10 to below 18 years old and are currently taking metformin, insulin, or both drugs.

Dapagliflozin and saxagliptin are both approved for use in patients with Type 2 Diabetes aged 18 years or older. Dapagliflozin (alone or in combination with other antidiabetic drugs) is available for use in adults in approximately 40 countries worldwide including the USA and Europe. Saxagliptin (alone or in combination with other antidiabetic drugs) is available for use in adults in approximately 90 countries worldwide. This study will assess how well dapagliflozin and saxagliptin work by finding out how these treatments affect blood glucose (sugar) levels compared to placebo (a pill that contains no active drug), in children and adolescents. Dapagliflozin and saxagliptin are considered investigational products in this study since while they have been approved for use in adults (patients 18 years or older), they haven't been approved for children and adolescents due to lack of clinical studies in this specific population.

Patients with Type 2 Diabetes have higher levels of blood glucose (sugar) than patients who do not have this disease. The high level of sugar in the blood can lead to serious short-term and long-term medical problems. The main goal of treating diabetic patients is to lower blood glucose to a normal level. Lowering and controlling blood glucose help prevent or delay complications of diabetes, such as heart disease, kidney, eye and nerve diseases, and the possibility of amputation.

Dapagliflozin is a drug that helps to reduce blood glucose (sugar) levels by helping the kidneys to remove excess glucose from the blood and excrete it in the urine. It prevents the kidneys from returning glucose from the urine back into the bloodstream.

Saxagliptin increases insulin production when blood glucose levels are high. Insulin is a hormone made by the pancreas that allows the body to use sugar (glucose) from the food that is eaten for energy or to store glucose for future use. Saxagliptin helps to improve blood sugar levels in response to a meal and between meals if blood glucose levels are not lowered effectively. Saxagliptin does not work when the blood glucose is low. Saxagliptin also helps to decrease the amount of sugar made by the body. Together, these processes reduce blood glucose levels and help to control Type 2 Diabetes.

The subject will either receive one of the active study drugs or a placebo (a pill that looks identical but contains inactive drug). This study will be double blind; this means that neither the subject, nor the study doctor will know which treatment the subject will receive.

Which treatment the subject receives is decided by a computer, purely by chance; this is called a "random assignment".

For this study, there will first be a screening phase of up to 6 months if Investigator thinks that some of the screening tests can be repeated, followed by a 2 week lead in phase. Thereafter there will be a 26W short-term treatment phase (W1-26), and a 26 W long-term treatment phase (W27-52). Following this there will be a follow-up telephone call on week 56 and a post study visit at W104. At day 1 visit after the lead in phase the subject will be randomly assigned to receive one of 3 treatments: dapagliflozin 5 mg, saxagliptin 2.5 mg or placebo in a blinded manner. This treatment will continue up to week 14. Then after week 14, and until the end of the study, the subject will be assigned to receive one of the following 5 treatments: dapagliflozin 5 mg, dapagliflozin 10 mg, saxagliptin 2.5 mg, saxagliptin 5 mg or placebo in a blinded manner. The drugs assigned after week 14 will be the same drugs as at Day 1, but some of the groups will receive them at a higher dose.Starting at W32 or W40, i.e., after the end of the primary endpoints, patients with background medication of metformin only, and an HbA1c value < 7.5% at W26 or W32, will undergo a third randomization. Eligible subjects from the treatment arms will undergo the randomized withdrawal of background medication, while eligible patients from the placebo arm will undergo, in addition to randomized withdrawal of background medication a randomized switch to active treatment.

Short- and long-term period study visits can be delayed by a maximum of 11 months in total. If the duration of investigational product administration is longer than 52 (+1) weeks, the safety follow-up period should be shortened such that the complete study duration does not exceed 104 weeks. The W104 visit should not be delayed.If more than 12 weeks elapse between the HbA1c collection at W26 and the third rand at W32, or the HbA1c collection at W32 and the third rand at W40, the subject should not go through this rand as the HbA1c value would no longer be reliable to ascertain eligibility for the third rand

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Placebo	Phase 3

Detailed Description:

In pediatric Type 2 Diabetes Mellitus (T2DM) subjects on diet and exercise and metformin, or insulin, or metformin and insulin:

The primary research hypothesis for dapagliflozin is whether addition of dapagliflozin, including up-titration if needed, results in a greater mean reduction from baseline in glycosylated hemoglobin (HbA1c) as compared to placebo when each are administered over 26 weeks of oral double-blind add-on treatment.

The primary research hypothesis for saxagliptin is whether addition of saxagliptin, including up-titration if needed, results in a greater mean reduction from baseline in HbA1c as compared to placebo when each are administered over 26 weeks of oral double-blind add-on treatment.

Study Design: The proposed study is a 26-week Phase 3b, multicenter, randomized, placebo-controlled, double-blind, parallel group study with a 26-week safety extension period to evaluate the safety and efficacy of dapagliflozin (5 mg and 10 mg), and, separately, saxagliptin (2.5 mg and 5 mg) in pediatric subjects with T2DM, and an additional post study visit at Week 104 for assessment of measures of growth and maturity. Approximately 243 pediatric subjects will be randomized in a 1:1:1 ratio to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Approximately 81 subjects will be randomized to each treatment arm.

After a 26-week, double-blind, ST treatment period, the primary efficacy endpoint will be assessed. This will be followed by a 26-week, site- and subject-blind LT safety extension period. Dapagliflozin and, separately, saxagliptin will be compared against the single shared placebo comparator.

Measures of growth and maturity will be assessed at the Week 104 post study visit.

Subjects will be required to have been treated with diet and exercise and a stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or a stable baseline dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin and insulin for a minimum of 8 weeks prior to randomization. At least 50% of subjects will be on a stable baseline dose of metformin, with or without concurrent insulin therapy. 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.

During the 2-week lead-in period, subjects will be instructed on a diet and exercise program (in accordance with the American Diabetes Association [ADA] or similar local guidelines) to be followed for the study duration. Subjects will maintain their baseline types and/or doses of antidiabetic therapy throughout the study (2-week lead-in, 26-week double-blind ST treatment period, and the 26-week blinded safety extension LT treatment period). If applicable, investigators will encourage subjects to keep their insulin doses stable. Down-titration of insulin will be allowed only as necessary to prevent hypoglycemia and will be at the discretion of the Investigator. Home glucose meters to monitor glucose control will be dispensed to subjects and self-blood glucose monitoring (SBGM) requirements and procedures will be explained. Subjects will also be instructed on the use of the subject diary to record self-monitored glucose levels and daily insulin dose, if applicable. Subjects will also receive a blood ketone meter for testing when DKA is suspected.

After the lead-in period, eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized 1:1:1 to receive oral, double-blind, dapagliflozin 5 mg (approximately 81 subjects), saxagliptin 2.5 mg (approximately 81 subjects), or placebo (approximately 81 subjects). Randomization will be stratified based on baseline anti-diabetes treatment regimen (stable baseline dose of metformin (IR or XR), a stable baseline dose of insulin, or a stable combination of metformin and insulin), gender, and age (10 to below 15 years of age, 15 to below 18 years of age).

A blinded HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c values < 7% will remain on previously assigned randomized treatment (dapagliflozin 5 mg, or saxagliptin 2.5 mg, or placebo) after the Week 12 assessment. Subjects assigned to the dapagliflozin treatment arm at Day 1 Randomization with Week 12 HbA1c values >= 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) after the Week 12 assessment. Similarly, subjects assigned to the saxagliptin treatment arm at Day 1 Randomization with Week 12 HbA1c values >= 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) after the Week 12 assessment. Subjects assigned to the placebo treatment arm at Day 1 Randomization with Week 12 HbA1c values >= 7% will continue on placebo treatment. To maintain the blinding of treatments as well as HbA1c results, all placebo subjects and all subjects taking saxagliptin or dapagliflozin with an HbA1c < 7% at week 12 will go through a dummy 2nd randomization process that will be indistinguishable (for the subjects and site personnel) from the actual 2nd randomization. During the Week 14 visit, blinded study drug will be dispensed to all subjects in accordance with new treatment assignments based on Week 12 HbA1c assessments. After completion of assessments at Week 26, a subset of eligible subjects who are receiving background medication with metformin only will undergo a third randomization (randomized withdrawal of background medication) at either Week 32 or Week 40. Eligibility for randomized withdrawal from background medication will be restricted to subjects who are receiving background treatment with metformin only, and who have HbA1c < 7.5% at Week 26 or Week 32 provided they have not initiated rescue glycemic control therapy or been withdrawn from study drug. Subjects who are receiving background medication with metformin only, who do not qualify for the third randomization at Week 32 due to an HbA1c ≥ 7.5% at Week 26, may qualify for the third randomization at Week 40 if HbA1c < 7.5% at Week 32. Subjects who have passed Week 40 will not be included in the randomized withdrawal of background medication

After completion of the ST treatment period, all subjects will enter the LT treatment period. All subjects, including those randomized to receive placebo, will continue with their randomized study medication assigned after the Week 12 assessment in the site- and subject blind LT treatment period. Adverse events (AEs) and serious adverse events (SAEs) will be assessed during a Week 56 phone visit.In case a visit is delayed for any reason, subsequent visits should be scheduled such that an interval of at least 12 weeks is maintained between the:

• Week 14 visit and the Week 26 visit.
• Third randomization (for subjects undergoing third randomization; occurring at the Week 32 or the Week 40 visit) and the Week 52 visit.

If more than 12 weeks elapse between the HbA1c collection at Week 26 and the third randomization at Week 32, or the HbA1c collection at Week 32 and the third randomization at Week 40, the subject should not go through this randomization as the HbA1c value would no longer be reliable to ascertain eligibility for the third randomization. Short- and long term period study visits can be delayed by a maximum of 11 months in total. If the duration of IP administration is longer than 52 (+1) weeks, the safety follow-up period should be shortened such that the complete study duration does not exceed 104 weeks.

Subjects who discontinue study drug before the end of the study treatment period will enter a non-treatment, follow up phase, in which subjects will follow their visit schedules with modified assessments until study completion. Subjects will attend a post-study visit at Week 104, for assessment of measures of growth and maturity.This visit should be completed without delay (at 104 weeks from Day 1 + 7 days), regardless of whether any other study visits were delayed.

If scheduled visits at clinical sites will be significantly impacted by the COVID-19 pandemic (e.g., there is a risk that the subject may be exposed to COVID-19 when visiting the site), home visits by study site personnel/vendor are allowed in countries where this is logistically feasible and considered acceptable. Before such a visit, a risk assessment that considers the potential risks to both the subject and the study personnel has to be performed.

Discontinued subjects will not be replaced. Samples for analysis of plasma levels of dapagliflozin, saxagliptin and its metabolite 5-Hydroxy saxagliptin (5 OH saxagliptin) will be collected pre-dose and approximately 2 hours post-dose (+/- 1 hour) during the Week 6, 12, 20, and 26 visits.

Samples for analysis of plasma glucose will be collected pre-dose during the Day 1 visit, and pre-dose and approximately 2 hours post-dose (+/- 1 hour) during the Week 6, 12, 20, and 26 visits.

Plasma samples for analysis of dipeptidyl peptidase-4 (DPP-4) activity will be collected pre-dose during the Day 1 visit, and at 2 (+/-1) hours post-dose during the Week 6, 12, 20, and 26 visits.Samples may be collected at additional time points during the study if warranted and agreed upon between the investigator and the Sponsor, eg, for safety reasons.

All plasma samples will be drawn in the fasting condition. During the course of the trial, subjects may be eligible for the addition of open-label rescue medication to their blinded treatment regimen in order to treat ongoing hyperglycemia. Insulin may be used as rescue, at the Investigator's discretion.

Pre-specified glycemic criteria, based upon self-monitored blood glucose (SMBG) FPG, or single central laboratory FPG and repeat confirmatory FPG have been established during the treatment period, starting at Week 6, and up to but not including the Week 52 visit, to determine eligibility for open-label rescue medication.

Sample Size:

The sample size for this study was selected to be consistent with the research hypotheses.

Dapagliflozin and saxagliptin will be compared with placebo separately. The Bonferroni method to control the type 1 error rate across two comparisons with respect to the two groups of research hypotheses (dapagliflozin vs placebo and saxagliptin vs placebo) will be used. No comparisons between saxagliptin and dapagliflozin will be performed.

The sample size for this study is based on the ability to detect a 0.5% improvement over placebo for dapagliflozin and saxagliptin in change from baseline in HbA1c at Week 26 (ST) with at least 80% power for each comparison at a two sided alpha level of 0.025. Assuming a standard deviation of 0.9% for change from baseline HbA1c at Week 26, a total of 237 pediatric subjects will be randomized in a 1:1:1 ratio to receive dapagliflozin 5 mg (79 subjects), saxagliptin 2.5 mg (79 subjects), or placebo (79 subjects) respectively. Assuming that 2% of subjectsdo not have a primary endpoint, a total of approximately 243 subjects will be randomized. Randomization will be stratified based on the baseline anti-diabetic treatment regimen (stable baseline dose of metformin [IR or XR]), a stable baseline dose of insulin, or a stable combination of metformin [IR or XR] and insulin), gender, and age (10 to below 15 years of age, 15 to below 18 years of age).

The anticipated difference of 0.5% between each study drug (saxagliptin and dapagliflozin) and placebo used in sample size estimation is consistent with estimates that were obtained in adult clinical trials with saxagliptin or dapagliflozin as add on to anti-diabetic medication where the primary endpoint was improvement in HbA1c after 24 weeks treatment. The standard deviation estimate of 0.9% is consistent with estimates obtained in these adult studies as well as with published estimates from pediatric trials of other anti-diabetic medications.

Analyses:

Dapagliflozin and saxagliptin will be summarized separately. A common placebo group will be included in each summary.

In addition, within the analyses of saxagliptin, the overall (combined low-dose and high-dose) efficacy and safety analyses will be repeated for the subgroup of subjects on a stable baseline dose of metformin (IR or XR) (with or without insulin). For these analyses, the saxagliptin treatment regimens will be combined into one group and compared to the (common) placebo group. P values corresponding to subgroup comparisons will be reported for the primary and secondary efficacy endpoints, and will be reported at the nominal significance level.

All efficacy analyses will be performed using the Randomized Subjects Data Set (all randomized subjects who receive at least one dose of study medication during the treatment period) unless otherwise specified.

The following treatment regimens are considered for analysis:

• Low-dose/high-dose: Initial treatment of the low-dose followed by up-titrating to the high-dose for those who do not achieve the glycemic target of HbA1c <7% at week 12
• Low-dose: Initial treatment of the low-dose followed by continuing treatment on the low-dose drug for those who do not achieve the glycemic target of HbA1c <7% at week 12 For each drug, the primary comparison between the low-dose/high-dose and placebo regimens will be tested at a two sided alpha level of 0.025.

The primary efficacy analysis will be performed using a weighted analysis of covariance (ANCOVA). Separate models will be used for saxagliptin and dapagliflozin analyses, and each analysis will include the (common) placebo control. Each model will have terms for baseline value, treatment group, and randomization strata.

For the comparison of the low-dose/high-dose treatment regimen versus placebo, all subjects who had HbA1c<7% at Week 12 and remained on the low-dose will get a weight of one. The subjects who had HbA1c >= 7% at Week 12 and continued on the low-dose will get a weight of 0. The subjects who had HbA1c>= 7% at Week 12 and received the high-dose will have a weight of 2. All subjects who do not undergo the second randomization and all placebo subjects will get a weight of one. The intent-to-treat (ITT) estimand will be evaluated as the primary estimand. Missing values for Week 26 will be imputed using the multiple imputation method. The details of the imputation method will be presented in the statistical analysis plan. Point estimates and 95% confidence intervals will be calculated based on maximum likelihood for the adjusted mean changes within each treatment group as well as for the differences in adjusted mean changes between treatment groups.

To assess the robustness of the primary efficacy analysis for the change in HbA1c from baseline to Week 26, additional sensitivity analysis may be performed using the Evaluable Subjects Data Set if > 10% of the subjects in any treatment group in the Randomized Subjects Data Set have relevant protocol deviations.

The primary endpoint will also be compared between the low-dose treatment regimen and placebo. In addition, up titrating to high-dose and continuing on low-dose will be compared in the subset of saxagliptin and dapagliflozin subjects who had HbA1c >= 7% at Week 12. These analyses are described under secondary efficacy analyses.

Secondary efficacy analyses will also be performed separately for each drug (saxagliptin and dapagliflozin). For each drug, the following sequential testing order will be employed to control multiplicity of testing for the secondary objectives.

1. Comparison of mean reduction in HbA1c from baseline at Week 26 between the low-dose treatment regimen and placebo
2. Comparison of mean reduction in HbA1c from baseline at Week 26 between overall drug treatment and placebo
3. Comparison of mean reduction in FPG from baseline at Week 26 between the low dose/high-dose treatment regimen and placebo
4. Comparison of mean reduction in FPG from baseline at Week 26 between the low-dose treatment regimen and placebo
5. Comparison of mean reduction in FPG from baseline at Week 26 between overall drug treatment and placebo
6. Comparison of the percentage of subjects with baseline HbA1c>= 7% who achieve an HbA1c level < 7.0% at Week 26 between the low-dose/high-dose treatment regimen and placebo
7. Comparison of the percentage of subjects with baseline HbA1c >= 7% who achieve an HbA1c level < 7.0% at Week 26 between the low-dose treatment regimen and placebo
8. Comparison of the percentage of subjects with baseline HbA1c >= 7% who achieve an HbA1c level < 7.0% at Week 26 between overall drug treatment and placebo
9. Comparison of mean reduction in HbA1c from baseline at Week 26 between the high dose and the low-dose in subjects who do not achieve an HbA1c < 7% at Week 12
10. Comparison of mean reduction in FPG from baseline at Week 26 between the high dose and the low-dose in subjects who do not achieve an HbA1c < 7% at Week 12
11. Comparison of the percentage of subjects with baseline HbA1c >= 7% who achieve an HbA1c level < 7.0% at Week 26 between the high-dose and the low-dose in subjects who do not achieve an HbA1c < 7% at Week 12 When the sequential testing stops for non-significance, nominal p-values and adjusted means will be provided for the remaining comparisons.

For each drug, weighted ANCOVA analysis will be performed for the change from baseline in HbA1c at Week 26 to compare the placebo and the low-dose treatment regimen. For this analysis, all subjects who had HbA1c < 7% at Week 12 and remained on the low-dose will get a weight of one. The subjects who had HbA1c >= 7% at Week 12 and continued on the low-dose will get a weight of 2. The subjects who had HbA1c >= 7% at Week 12 and received the high-dose will have a weight of 0. All subjects who do not undergo the second randomization and all placebo subjects will get a weight of one.

For subjects on saxagliptin and dapagliflozin and who had HbA1c >= 7% at Week 12, the change from baseline HbA1c at Week 26 (ST) will be compared between the subjects re-randomized to remain on the low-dose and the subjects who are re-randomized to the high- dose using an ANCOVA.

Change from baseline of HbA1c at Week 26 (ST) will be compared also using a repeated measures analysis between overall drug and placebo. For this analysis, both treatment regimens will be combined into one treatment group for each drug.

Change from baseline at Week 26 (ST) in FPG will be analyzed similar to the primary weighted analyses of change from baseline in HbA1c at Week 26.

The proportion of subjects achieving HbA1c < 7.0% at Week 26 (ST) will be analyzed using weighted logistic regression with adjustment for the baseline HbA1c measurement and the randomization strata. Weighting for the subjects will be applied similarly to a weighting in the analysis of change from baseline in HbA1c. Subjects with missing a response at Week 26 will be imputed by dichotomizing the imputed values of HbA1c at Week 26.

The assessment of safety will be based on the analyses of AEs, vital signs, physical examinations, electrocardiograms, hypoglycemia, DKA, safety laboratory evaluations, and measures of growth and maturity. All safety analyses will be performed using the Treated Subjects Data Set. Dapagliflozin and saxagliptin will be summarized separately. Treatment regimens (low-dose or low-dose/high-dose) will be combined for saxagliptin and dapagliflozin to provide the safety summary for overall saxagliptin and overall dapagliflozin compared to placebo. A common placebo group will be included in each summary.

Measures of growth, bone and maturation markers will also be summarized for the combined ST + LT + additional post study visit at Week 104.

Monitoring The Sponsor/designee representatives will review data centrally to identify potential issues to determine a schedule of on-site visits for targeted review of study records.

Representatives of the Sponsor (or designee) must be allowed to visit all study site locations periodically to assess the data quality and study integrity. On site they will review study records and directly compare them with source documents, discuss the conduct of the study with the Investigator, and verify that the facilities remain acceptable.Off-site monitoring visits and remote source data verification are allowed when restrictions due to the COVID-19 pandemic prevent on site visits (e.g., monitors may not be able to access the sites in a timely manner). Should this occur, it should be documented and the reasons be available for review by the Sponsor and during inspections by any Regulatory Authorities In addition, the study may be evaluated by the Sponsor (or designee) internal auditors and government inspectors who must be allowed access to Case Report Forms (CRFs), source documents, other study files, and study facilities. The Sponsor (or designee) audit reports will be kept confidential.

The investigator must notify the Sponsor (or designee) promptly of any inspections scheduled by regulatory authorities, and promptly forward copies of inspection reports to the Sponsor/designee.

Records Retention The investigator must retain all study records and source documents for the maximum period required by applicable regulations and guidelines, or institution procedures, or for the period specified by the Sponsor/designee, whichever is longer. The investigator must contact the Sponsor/designee prior to destroying any records associated with the study.

The Sponsor/designee will notify the Investigator when the study records are no longer needed.

If the Investigator withdraws from the study (e.g., relocation, retirement), the records shall be transferred to a mutually agreed upon designee (e.g., another investigator, IRB). Notice of such transfer will be given in writing to the Sponsor/designee.

Study Drug Records

It is the responsibility of the Investigator to ensure that a current disposition record of study drug (inventoried and dispensed) is maintained at the study site to include Investigational Products (IPs). Except where the IP has to be sent directly to the subjects' homes due to the coronavirus disease 2019 (COVID 19) pandemic. Any unused IP sent directly to subjects' homes should be returned to the site at the next on-site visit.Records or logs must comply with applicable regulations and guidelines and should include:

• Amount received and placed in storage area
• Amount currently in storage area
• Label identification number or batch number
• Amount dispensed to and returned by each subject, including unique subject identifiers
• Amount transferred to another area/site for dispensing or storage
• Non study disposition (e.g., lost, wasted)
• Amount destroyed at study site, if applicable
• Amount returned to the Sponsor/designee
• Retain samples for bioavailability/bioequivalence, if applicable
• Dates and initials of person responsible for IP dispensing/accountability, as per the Delegation of Authority Form The Sponsor/designee will provide forms to facilitate inventory control if the investigational site does not have an established system that meets these requirements.

Case Report Forms An investigator is required to prepare and maintain adequate and accurate case histories designed to record all observations and other data pertinent to the investigation on each individual treated or entered as a control in the investigation. Data that are derived from source documents and reported on the CRF must be consistent with the source documents or the discrepancies must be explained. Additional clinical information may be collected and analyzed in an effort to enhance understanding of product safety. Case report forms may be requested for AEs and/or laboratory abnormalities that are reported or identified during the course of the study.

For sites using the Sponsor/designee's Electronic Data Capture (EDC) tool, electronic CRFs will be prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will be reported on the electronic SAE form and Pregnancy Surveillance Form, respectively. If electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank only in those circumstances permitted by study-specific CRF completion guidelines provided by the Sponsor/designee.

The confidentiality of records that could identify subjects must be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).

The investigator will maintain a signature sheet to document signatures and initials of all persons authorized to make entries and/or corrections on CRFs.

The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the Investigator or qualified physician who is a co-investigator and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review and approval/signature is completed electronically through the Sponsor/designee's EDC tool. The investigator must retain a copy of the CRFs including records of the changes and corrections.Data entered in the eCRF that are transcribed from source documents must be consistent with the source documents or the discrepancies must be explained.

Each individual electronically signing electronic CRFs must meet Sponsor/designee training requirements and must only access the Sponsor/designee's EDC tool using the unique user account provided by the Sponsor/designee. User accounts are not to be shared or reassigned to other individuals.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 243 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Investigator)
• Masking Description: sponsor
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 11, 2017
• Estimated Primary Completion Date: September 20, 2022
• Estimated Study Completion Date: August 21, 2023

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Dapagliflozin; Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily; Other Name: Forxiga
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	Drug: Dapagliflozin; Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily; Other Name: Forxiga
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	Drug: Saxagliptin; Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily; Other Name: Onglyza
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	Drug: Saxagliptin; Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily; Other Name: Onglyza
Placebo Comparator: Placebo arm; Oral route. Placebo tablets administered for 52 weeks	Drug: Placebo; Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change from baseline in Fasting Plasma Glucose at Week 26 [ Time Frame: 26 weeks ]
   To determine if there will be a greater mean reduction from baseline in Fasting Plasma Glucose (FPG) 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 of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin
2. Percentage of subjects with baseline HbA1c ≥ 7%, who achieve an HbA1c level < 7.0% at Week 26 [ Time Frame: 26 weeks ]
   To compare the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% 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) versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

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 [ Time Frame: 26 weeks ]
   To compare the percentage of subjects requiring glycemic rescue medication or discontinuing study medication due to lack of efficacy with dapagliflozin or saxagliptin against the percentage with placebo during 26 weeks of oral double-blind add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.
2. Change from baseline in HbA1c at Week 52 [ Time Frame: 52 weeks ]
   To assess the mean change from baseline in HbA1c achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.
3. Change from baseline in FPG at Week 52 [ Time Frame: 52 weeks ]
   To assess the mean change from baseline in FPG achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin
4. Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% at Week 52 [ Time Frame: 52 weeks ]
   To assess the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% after 52 weeks of oral blinded add-on therapy with dapagliflozin versus placebo, or saxagliptin versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed Written Informed Consent
• Target Population
• Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria
• HbA1c between 6.5% and 10.5% obtained at screening.
• Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject's therapeutic regimen had been previously made but had not been successful.
• Age and Reproductive Status
• Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects.
• Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
• Women must not be breastfeeding.
• Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion.

Exclusion Criteria:

• Target Disease Exceptions
• Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
• Previous diagnosis of monogenic etiology of Type 2 diabetes
• Diabetes ketoacidosis (DKA) within 6 months of screening
• Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
• Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
• Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)
• Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study.
• Medical History and Concurrent Diseases
• Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
• History of unstable or rapidly progressive renal disease
• History of unresolved vesico-ureteral reflux
• History of or current, acute or chronic pancreatitis
• History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
• Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
• Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to the Day 1 visit
• Physical and Laboratory Test Findings
• Abnormal renal function,
• An abnormal thyroid-stimulating hormone (TSH) value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded.
• Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of normal (ULN), or clinically significant hepatic disease.
• Serum total bilirubin (TB) > 2x ULN unless exclusively caused by Gilbert's syndrome
• Positive serologic evidence of current infectious liver disease including anti hepatitis A virus (HAV) (IgM), hepatitis B surface antigen (HBsAg), or anti hepatitis C virus (HCV). Patients who have isolated positive anti-hepatitis B surface antibodies may be included.
• Anemia of any etiology
• Volume-depleted subjects.
• Allergies and Adverse Drug Reaction
• Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
• Other Exclusion Criteria
• Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
• Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Sponsor/designee approval is required.)
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
• Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.
• Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
• Participation and receiving IP in another clinical study during the prior 3 months

Contacts and Locations

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

Locations

United States, Alabama

Research Site; Withdrawn

Saraland, Alabama, United States, 36571

United States, California

Research Site; Recruiting

Huntington Park, California, United States, 90255

Research Site; Recruiting

Long Beach, California, United States, 90806

Research Site; Recruiting

Sacramento, California, United States, 95821

United States, District of Columbia

Research Site; Withdrawn

Washington, District of Columbia, United States, 20032

United States, Florida

Research Site; Recruiting

Hialeah, Florida, United States, 33012

Research Site; Recruiting

Hialeah, Florida, United States, 33016

Research Site; Recruiting

Hollywood, Florida, United States, 33021

Research Site; Recruiting

Miami Springs, Florida, United States, 33166

Research Site; Withdrawn

Miami, Florida, United States, 33015

Research Site; Recruiting

Miami, Florida, United States, 33144

Research Site; Recruiting

Miami, Florida, United States, 33155

Research Site; Recruiting

Miami, Florida, United States, 33165

Research Site; Recruiting

Miami, Florida, United States, 33173

Research Site; Withdrawn

Spring Hill, Florida, United States, 34609

United States, Georgia

Research Site; Recruiting

Chamblee, Georgia, United States, 30341

Research Site; Recruiting

Norcross, Georgia, United States, 30093

Research Site; Withdrawn

Stockbridge, Georgia, United States, 30281

United States, Idaho

Research Site; Recruiting

Idaho Falls, Idaho, United States, 83404-7596

United States, Louisiana

Research Site; Recruiting

New Orleans, Louisiana, United States, 70125

United States, Massachusetts

Research Site; Withdrawn

Springfield, Massachusetts, United States, 01199-1001

United States, New Jersey

Research Site; Recruiting

Neptune, New Jersey, United States, 07753

United States, New York

Research Site; Recruiting

New York, New York, United States, 10029

United States, South Carolina

Research Site; Withdrawn

Charleston, South Carolina, United States, 29407

United States, Tennessee

Research Site; Withdrawn

Memphis, Tennessee, United States, 38116

Research Site; Recruiting

Memphis, Tennessee, United States, 38116

Research Site; Withdrawn

Memphis, Tennessee, United States, 38119

Research Site; Recruiting

Memphis, Tennessee, United States, 38119

United States, Texas

Research Site; Recruiting

Edinburg, Texas, United States, 78539

Research Site; Withdrawn

McAllen, Texas, United States, 78503

Research Site; Recruiting

McAllen, Texas, United States, 78503

Research Site; Recruiting

San Antonio, Texas, United States, 78229

United States, Washington

Research Site; Withdrawn

Bellevue, Washington, United States, 98007

Research Site; Withdrawn

Tacoma, Washington, United States, 98405

Argentina

Research Site; Recruiting

Buenos Aires, Argentina, 6500

Research Site; Recruiting

Buenos Aires, Argentina, C1180AAX

Research Site; Recruiting

Caba, Argentina, C1119ACN

Research Site; Recruiting

Ciudad Autonoma de Buenos Aire, Argentina, C1407GTN

Research Site; Recruiting

Ciudad de Buenos Aires, Argentina, C1405BCH

Research Site; Completed

San Miguel de Tucumán, Argentina, 4000

Research Site; Recruiting

San Miguel de Tucumán, Argentina, T4000IHE

Australia

Research Site; Recruiting

Blacktown, Australia, 2148

Research Site; Withdrawn

Nedlands, Australia, 6009

Brazil

Research Site; Recruiting

Belem, Brazil, 66073-005

Research Site; Recruiting

Brasilia, Brazil, 71625-009

Research Site; Recruiting

Campinas, Brazil, 13020-431

Research Site; Recruiting

Curitiba, Brazil, 80810-040

Research Site; Recruiting

Fortaleza, Brazil, 60170-320

Research Site; Recruiting

Fortaleza, Brazil, 60430-270

Research Site; Withdrawn

Goiânia, Brazil, 74110-010

Research Site; Withdrawn

Marília, Brazil, 17519-230

Research Site; Recruiting

Passo Fundo, Brazil, 99010-080

Research Site; Withdrawn

Porto Alegre, Brazil, 90035-170

Research Site; Recruiting

Porto Alegre, Brazil, 90430-001

Research Site; Recruiting

Porto Alegre, Brazil, 91350-250

Research Site; Recruiting

Ribeirão Preto, Brazil, 14051-104

Research Site; Recruiting

Santa Maria, Brazil, 97015-530

Research Site; Recruiting

Sao Paulo, Brazil, 01223-001

Research Site; Recruiting

Sao Paulo, Brazil, 05652-900

Research Site; Recruiting

Uberaba, Brazil, 38025-260

Canada, British Columbia

Research Site; Withdrawn

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Ontario

Research Site; Withdrawn

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

Research Site; Recruiting

Montreal, Quebec, Canada, H1T 2M4

Research Site; Recruiting

Montreal, Quebec, Canada, H4A 3J1

Chile

Research Site; Withdrawn

Antofagasta, Chile

Research Site; Recruiting

San Bernardo, Chile, 8050000

Research Site; Recruiting

Santiago, Chile, 7500701

Research Site; Withdrawn

Santiago, Chile, 8910108

China

Research Site; Withdrawn

Beijing, China, 100045

Colombia

Research Site; Recruiting

Armenia, Colombia, 630004

Research Site; Recruiting

Barranquilla, Colombia, 80020

Research Site; Recruiting

Bogotá, Colombia, 110221

Research Site; Withdrawn

Bogotá, Colombia

Research Site; Recruiting

Medellin, Colombia, 050022

Finland

Research Site; Recruiting

Kuopio, Finland, 70029 KYS

Research Site; Recruiting

Seinäjoki, Finland, 60100

Research Site; Recruiting

Tampere, Finland, 33520

India

Research Site; Recruiting

Ahmedabad, India, 380008

Research Site; Recruiting

Aurangabad, India, 431003

Research Site; Recruiting

Bangalore, India, 560002

Research Site; Recruiting

Bangalore, India, 560054

Research Site; Recruiting

Bikaner, India, 334003

Research Site; Recruiting

Chandigarh, India, 160012

Research Site; Recruiting

Coimbatore, India, 641009

Research Site; Recruiting

Hyderabad, India, 500012

Research Site; Recruiting

Kolkata, India, 700054

Research Site; Recruiting

Kozhikode, India, 67300

Research Site; Recruiting

Nagpur, India, 440003

Research Site; Recruiting

Nashik, India, 422002

Research Site; Recruiting

Pune, India, 411030

Research Site; Recruiting

Vadodara, India, 390001

Research Site; Recruiting

Visakhapatnam, India, 530002

Israel

Research Site; Recruiting

Haifa, Israel, 3109601

Italy

Research Site; Recruiting

Ancona, Italy, 60123

Research Site; Recruiting

Modena, Italy, 41124

Research Site; Recruiting

Napoli, Italy, 80138

Research Site; Recruiting

Roma, Italy, 00128

Research Site; Recruiting

Roma, Italy, 00165

Research Site; Recruiting

Roma, Italy, 00185

Korea, Republic of

Research Site; Recruiting

Daejeon-si, Korea, Republic of, 35233

Research Site; Recruiting

Incheon, Korea, Republic of, 22332

Research Site; Recruiting

Seongnam-si, Korea, Republic of, 13620

Research Site; Recruiting

Seoul, Korea, Republic of, 05030

Research Site; Withdrawn

Seoul, Korea, Republic of, 06273

Research Site; Recruiting

Wonju-si, Korea, Republic of, 26426

Malaysia

Research Site; Recruiting

George Town, Malaysia, 10450

Research Site; Recruiting

Ipoh, Malaysia, 30990

Research Site; Recruiting

Johor Bahru, Malaysia, 80100

Research Site; Recruiting

Klang, Malaysia, 41200

Research Site; Recruiting

Kota Kinabalu, Malaysia, 88996

Research Site; Recruiting

Kuala Lumpur, Malaysia, 50586

Research Site; Recruiting

Kuching, Malaysia, 93586

Research Site; Recruiting

Melaka, Malaysia, 75400

Research Site; Recruiting

Putrajaya, Malaysia, 62250

Research Site; Recruiting

Seri Manjung, Malaysia, 32040

Research Site; Recruiting

Taiping, Malaysia, 34000

Mexico

Research Site; Recruiting

Boca del Rio, Mexico, 94290

Research Site; Recruiting

Celaya, Mexico, 38000

Research Site; Recruiting

Ciudad Madero, Mexico, 89440

Research Site; Recruiting

Cuernavaca, Mexico, 62209

Research Site; Recruiting

Cuernavaca, Mexico, 62290

Research Site; Recruiting

Culiacán, Mexico, 80230

Research Site; Recruiting

Durango, Mexico, 34000

Research Site; Recruiting

Guadalajara, Mexico, 44150

Research Site; Recruiting

Merida, Mexico, 97000

Research Site; Recruiting

Mexico, Mexico, 06700

Research Site; Recruiting

Monterrey, Mexico, 64460

Research Site; Recruiting

Monterrey, Mexico, 64620

Research Site; Recruiting

México, D.F., Mexico, 11410

Research Site; Recruiting

San Juan del Rio, Mexico, 76800

Research Site; Recruiting

Veracruz, Mexico, 91900

Research Site; Recruiting

Zapopan, Mexico, 45116

New Zealand

Research Site; Recruiting

Auckland, New Zealand, 0626

Research Site; Recruiting

Grafton, New Zealand, 1023

Research Site; Withdrawn

Havelock North, New Zealand, 6242

Research Site; Withdrawn

Papatoetoe, New Zealand, 2025

Research Site; Recruiting

Tauranga, New Zealand, 3110

Research Site; Recruiting

Wellington, New Zealand, 6021

Philippines

Research Site; Withdrawn

Cebu City, Philippines, 6000

Research Site; Withdrawn

Davao DEL SUR, Philippines, 8000

Research Site; Recruiting

Quezon City, Philippines, 1100

Research Site; Recruiting

Quezon City, Philippines, 1112

Research Site; Recruiting

San Fernando City, Philippines, 2000

Poland

Research Site; Withdrawn

Bydgoszcz, Poland, 85-667

Research Site; Recruiting

Kraków, Poland, 30-149

Research Site; Recruiting

Rzeszów, Poland, 35-301

Research Site; Recruiting

Warszawa, Poland, 01-868

Romania

Research Site; Recruiting

Bucuresti, Romania, 011025

Research Site; Recruiting

Bucuresti, Romania, 52034

Research Site; Recruiting

Dobrosloveni, Romania, 237143

Research Site; Withdrawn

Satu Mare, Romania, 440055

Research Site; Withdrawn

Timisoara, Romania, 300011

Russian Federation

Research Site; Withdrawn

Barnaul, Russian Federation, 656024

Research Site; Recruiting

Izhevsk, Russian Federation, 426009

Research Site; Withdrawn

Kemerovo, Russian Federation, 650066

Research Site; Recruiting

Moscow, Russian Federation, 117036

Research Site; Recruiting

Moscow, Russian Federation, 125993

Research Site; Withdrawn

Saint-Petersburg, Russian Federation, 197342

Research Site; Recruiting

Tomsk, Russian Federation, 634050

Research Site; Recruiting

Ufa, Russian Federation, 450000

Research Site; Withdrawn

Vologda, Russian Federation, 160022

Taiwan

Research Site; Recruiting

Taichung, Taiwan, 404

Research Site; Recruiting

Tainan City, Taiwan, 704

Research Site; Recruiting

Taipei, Taiwan, 112

Thailand

Research Site; Recruiting

Bangkok, Thailand, 10400

Research Site; Recruiting

Chiang Mai, Thailand, 50200

Research Site; Recruiting

Hat Yai, Thailand, 90110

Research Site; Recruiting

Muang, Thailand, 57000

Turkey

Research Site; Recruiting

Aydin, Turkey, 9010

Research Site; Recruiting

Bursa, Turkey, 16059

Research Site; Withdrawn

Duzce, Turkey, 81600

Research Site; Recruiting

Eskisehir, Turkey, 26480

Research Site; Recruiting

Istanbul, Turkey, 34020

Research Site; Withdrawn

Istanbul, Turkey, 34325

Research Site; Recruiting

Izmir, Turkey, 35210

Research Site; Recruiting

Izmir, Turkey, 35330

Research Site; Recruiting

Kocaeli, Turkey, 41380

Research Site; Recruiting

Kurupelit, Turkey, 55139

Research Site; Recruiting

Manisa, Turkey, 45030

Research Site; Recruiting

Trabzon, Turkey, 61080

Ukraine

Research Site; Recruiting

Chernivtsі, Ukraine, 58005

Research Site; Recruiting

Dnipro, Ukraine, 49023

Research Site; Recruiting

Kharkiv Region, Ukraine, 61093

Research Site; Withdrawn

Kharkiv Region, Ukraine, 61153

Research Site; Recruiting

Kyiv, Ukraine, 01021

Research Site; Recruiting

Poltava, Ukraine, 36011

Research Site; Recruiting

Sumy, Ukraine, 40031

Research Site; Recruiting

Vinnytsia, Ukraine, 21010

Research Site; Recruiting

Zaporizhzhia, Ukraine, 69063

United Kingdom

Research Site; Recruiting

Birmingham, United Kingdom, B4 6NH

Research Site; Recruiting

London, United Kingdom, E1 1BB

Research Site; Recruiting

London, United Kingdom, SE13 6LH

Research Site; Recruiting

London, United Kingdom, SE5 9RS

Research Site; Recruiting

Middlesbrough, United Kingdom, TS4 3BW

Research Site; Recruiting

Nottingham, United Kingdom, NG7 2UH

Sponsors and Collaborators

AstraZeneca

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03199053
• Other Study ID Numbers: D1680C00019; 2015-005042-66 ( EudraCT Number )
• First Posted: June 26, 2017
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

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 Materials: Study Protocol; Statistical Analysis Plan (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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:

Type 2 Diabetes Mellitus

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Saxagliptin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors