Type 2 Diabetes
Conditions
Keywords
Diabetes Mellitus, Dapagliflozin, Placebo, Insulin resistance, Metabolic Diseases
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
Interventions
DRUGDapagliflozin
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.
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.
Sponsors
Parexel
Q2 Solutions
PRA Health Sciences
Covance
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 24 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24 | Baseline to Week 24 |
Secondary
| 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 |
Countries
Hungary, Israel, Mexico, Romania, Russia, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 42 study centres in 7 countries worldwide.
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin 10mg/ Dapagliflozin 10mg Dapagliflozin (10 mg) tablet administered orally, once daily for the 24 week double-blinded treatment period. The participants then continued to receive Dapagliflozin (10 mg) once daily for a further 28 weeks in the open label long term-extension. | 39 |
| Placebo/ Dapagliflozin 10mg Matching placebo tablet administered orally, once daily for the 24 weeks double-blinded treatment period. The participants then received Dapagliflozin (10 mg), orally, once daily for a further 28 weeks in the open label long-term extension. | 33 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment Period | Lost to Follow-up | 1 | 1 |
| Blinded Treatment Period | Withdrawal by Parent/Guardian | 0 | 2 |
| Blinded Treatment Period | Withdrawal by Subject | 4 | 3 |
| Long Term Extension | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Dapagliflozin 10mg/ Dapagliflozin 10mg | Placebo/ Dapagliflozin 10mg | Total |
|---|---|---|---|
| Age, Continuous | 16.1 Years STANDARD_DEVIATION 3.3 | 16.2 Years STANDARD_DEVIATION 3.6 | 16.1 Years STANDARD_DEVIATION 3.4 |
| Age, Customized ≥10 and ≤15 | 16 Participants | 14 Participants | 30 Participants |
| Age, Customized >15 and <18 | 13 Participants | 10 Participants | 23 Participants |
| Age, Customized ≥18 and <25 | 10 Participants | 9 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 21 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Geographic Region Asia/Pacific | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region Europe | 16 Participants | 8 Participants | 24 Participants |
| Geographic Region Latin America | 7 Participants | 9 Participants | 16 Participants |
| Geographic Region North America | 16 Participants | 16 Participants | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 10 Participants | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 16 Participants | 44 Participants |
| Sex: Female, Male Female | 24 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 33 |
| other Total, other adverse events | 24 / 39 | 19 / 33 |
| serious Total, serious adverse events | 2 / 39 | 3 / 33 |
Outcome results
Primary
Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24
Time frame: Baseline to Week 24
Population: Full analysis set: All participants who were randomized and assigned to a treatment group, with baseline and at least one-post baseline value, prior to rescue therapy initiation or discontinuation from study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin 10mg/ Dapagliflozin 10mg | Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24 | -0.25 Percentage of HbA1c | Standard Error 0.3 |
| Placebo/ Dapagliflozin 10mg | Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24 | 0.50 Percentage of HbA1c | Standard Error 0.34 |
p-value: 0.10195% CI: [-1.65, 0.15]Mixed model repeated measures analysis
Secondary
Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Time frame: Baseline to Week 24
Population: Full analysis set: All participants who were randomized and assigned to a treatment group, with baseline and at least one-post baseline value, prior to rescue therapy initiation or discontinuation from study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin 10mg/ Dapagliflozin 10mg | Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -0.07 mmol/L | Standard Error 0.53 |
| Placebo/ Dapagliflozin 10mg | Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | 0.72 mmol/L | Standard Error 0.61 |
p-value: 0.3495% CI: [-2.42, 0.85]Mixed model repeated measures analysis
Secondary
Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control
Time frame: Baseline to Week 24
Population: Full analysis set: All participants who were randomized and assigned to a treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin 10mg/ Dapagliflozin 10mg | Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control | 5.1 Percentage of participants |
| Placebo/ Dapagliflozin 10mg | Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control | 9.1 Percentage of participants |
p-value: 0.65595% CI: [-20.11, 9.62]Fisher's exact test
Secondary
Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24
Time frame: Baseline to Week 24
Population: Full analysis set: All participants who were randomized and assigned to a treatment group, with HbA1c \>=7% at baseline, with baseline and at least one-post baseline value, prior to rescue therapy initiation or discontinuation from study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin 10mg/ Dapagliflozin 10mg | Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24 | 25.0 Percentage of participants |
| Placebo/ Dapagliflozin 10mg | Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24 | 4.2 Percentage of participants |
p-value: 0.05695% CI: [0.5, 41.11]Fisher's exact test