Clinical trial NCT02725593: Study to Evaluate Safety and Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Aged 10-24 Years
Official title: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: Diabetes Mellitus
Dapagliflozin
Placebo
Insulin resistance
Metabolic Diseases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
name: Q2 Solutions
name: PRA Health Sciences
name: Covance
First posted: 2016-04-01
Enrollment: 72
Sex: ALL
Minimum age (years): 10
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control
timeFrame: Baseline to Week 24
measure: Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Homestead
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Bronx
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Lampasas
country: United States
facility: Research Site
state: Texas
city: McAllen
country: United States
facility: Research Site
state: Texas
city: Budapest
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Beer Sheva
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Zerifin
country: Israel
facility: Research Site
city: Culiacan
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Merida
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: México, D.F.
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Kent
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: 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.