Study to Evaluate Safety and Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Aged 10-24 Years

A 24 Week, Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial With a 28 Week Long Term Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 10 mg in T2DM Patients Aged 10-24 Years

A trial of patients aged 10-24 years with type 2 diabetes mellitus to evaluate the comparative efficacy and safety between dapagliflozin and Placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Dapagliflozin placebo

Detailed Description

A 24 Week, Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial with a 28 Week Long Term Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 10 mg in T2DM Patients aged 10-24 years

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1023
    • Research Site
  • Nyíregyháza, Hungary, 4400
    • Research Site
• Israel
  • Beer Sheva, Israel, 84101
    • Research Site
  • Haifa, Israel, 91096
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
  • Zerifin, Israel, 70300
    • Research Site
• Mexico
  • Culiacan, Mexico, 80230
    • Research Site
  • Guadalajara, Mexico, 44670
    • Research Site
  • Merida, Mexico, 97134
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • México, D.F., Mexico, 11410
    • Research Site
  • Zapopan, Mexico, 45116
    • Research Site
• Romania
  • Oradea, Romania, 410169
    • Research Site
  • Timisoara, Romania, 300011
    • Research Site
• Russian Federation
  • Izhevsk, Russian Federation, 426009
    • Research Site
  • Krasnoyarsk, Russian Federation, 660022
    • Research Site
  • Moscow, Russian Federation, 117036
    • Research Site
  • Novosibirsk, Russian Federation, 630087
    • Research Site
  • Pyatigorsk, Russian Federation, 357500
    • Research Site
  • Rostov-on-Don, Russian Federation, 344022
    • Research Site
  • Samara, Russian Federation, 443079
    • Research Site
  • Saratov, Russian Federation, 410054
    • Research Site
  • St. Petersburg, Russian Federation, 194100
    • Research Site
  • Tomsk, Russian Federation, 634050
    • Research Site
• United Kingdom
  • Kent, United Kingdom, CT9 4AN
    • Research Site
  • Leicester, United Kingdom, LE15WW
    • Research Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06514-3434
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Research Site
    • Homestead, Florida, United States, 33032
      • Research Site
    • Miami, Florida, United States, 33015
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
    • Buffalo, New York, United States, 14222
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
    • Memphis, Tennessee, United States, 38116
      • Research Site
  • Texas
    • Lampasas, Texas, United States, 76550
      • Research Site
    • McAllen, Texas, United States, 78503
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Provision of informed consent prior to any study-specific procedures
2. Males and Females, ages 10 years of age, up to but not including 25 years of age at the time of randomization
3. Previously diagnosed as having type 2 diabetes for at least 2 months by WHO/ADA diagnostic criteria
4. HbA1c >= 6.5% and <= 11% obtained at screening visit
5. Currently on diet and exercise and a stable dose of metformin (at least 1000 mg daily) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of metformin (at least 1000 mg daily) and insulin for a minimum of 8 weeks prior to screening
6. FPG <=255 mg/dL (<= 14.2 mmol/L) obtained at screening visit

Exclusion Criteria:

1. Previous diagnosis of Type 1 diabetes
2. Diabetes ketoacidosis (DKA) within 6 months of screening

3. 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, or injectable incretins or incretin mimetics or other antidiabetes medications not otherwise specified
   • Sixteen weeks: thiazolidinediones
   • Any previous history or current use of an SGLT2 inhibitor, including dapagliflozin

4. 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

5. Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
6. History of unstable or rapidly progressive renal disease
7. History of unresolved vesico-ureteral reflux

8. 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.

   Note: Topical, nasal, or inhaled corticosteroids are allowed

9. Abnormal renal function, which is defined in subjects < 18 years of age as an estimated glomerular filtration rate (eGFR) calculated by the Schwartz Formula < 80 mL/min/1.73 m2 (1.33 mL/s), and in subjects >= 18 years as an estimated glomerular filtration rate (eGFR) calculated by the MDRD Formula < 60 mL/min/1.73 m2 (1.33 mL/s)
10. Presence of either: antibodies to glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein antibodies (IA-2)
11. An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded
12. Hematuria (confirmed by microscopy at screening) with no explanation as judged by the investigator up to randomization
13. Anemia of any etiology defined as hemoglobin <=10.7 g/dL (107 g/L) for females and <= 11.3 g/dL (113 g/L) for males. Subjects who are considered to have anemia according to local guidelines should be excluded
14. Volume-depleted subjects. Subjects at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics, should carefully monitor their volume status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin	Drug: Dapagliflozin; Dapagliflozin 10 mg tablets administered orally once daily, for the 24-week blinded treatment period. Dapagliflozin 10mg tablets administered orally once daily, for the 28-week site and subject blinded long term extension.; Other Names: FORXIGA
Placebo Comparator: Dapagliflozin placebo	Drug: Dapagliflozin placebo; matching placebo tablets, administered orally once daily, for the 24-week blinded treatment period. Dapagliflozin 10mg tablets administered orally once daily,for the 28-week site and subject blinded long term extension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Baseline to Week 24
Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control	Baseline to Week 24
Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24	Baseline to Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel; PRA Health Sciences; Q2 Solutions; Covance Laboratories, Inc

Publications and helpful links

General Publications

• Tamborlane WV, Laffel LM, Shehadeh N, Isganaitis E, Van Name M, Ratnayake J, Karlsson C, Norjavaara E. Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study. Lancet Diabetes Endocrinol. 2022 May;10(5):341-350. doi: 10.1016/S2213-8587(22)00052-3. Epub 2022 Apr 1.

Helpful Links

• D1690C00017_CSP_redacted
• D1690C00017_SAP_redacted

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2016
• Primary Completion (Actual): April 6, 2020
• Study Completion (Actual): April 6, 2020

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Insulin resistance; Dapagliflozin; Diabetes Mellitus; Placebo; Metabolic Diseases
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: D1690C00017; 2015-005041-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)