Type 2 Diabetes Mellitus
Conditions
Brief summary
A prospective, multicenter, phase -IV study to assess the safety of fixed dose combination of dapagliflozin and saxagliptin in Indian Type 2 Diabetes Mellitus (T2D) patients.
Detailed description
During the study, an AstraZeneca representative/delegate will have regular contacts with the study site, including visits to site for the site monitoring and source data verification activities. Electronic Case Report Forms (eCRF) will be used for data collection and query handling. The investigator will sign the completed electronic Case Report Forms. A copy of the completed electronic Case Report Forms will be archived at the study site. Authorized representatives of AstraZeneca or delegate, a regulatory authority, or an Ethics Committee may perform audits or inspections at the center's. Number and percentages of Incidence of adverse events will be presented, stratified by age/gender/baseline medications. Annualised event rate shall also be presented in addition to the incidence rate during the study. Mean change in HbA1C from baseline to 6 months for patients will be analysed using paired t test / Wilcoxon signed-rank test at 5% level of significance.
Interventions
DRUGdapagliflozin and saxagliptin
Combination of dapagliflozin and saxagliptin tablet once daily fixed dose combination of Dapa/Saxa 10 mg/5 mg administered orally
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study subjects should fulfil the following criteria: 1. Provision of signed and dated, written informed consent prior to any study specific procedures according to local Indian procedure. 2. Male and female patients aged \> 18 and above 3. Documented history of type 2 diabetes mellitus with HbA1c level \>7.0% and ≤ 10% at screening visit 4. Patients who are on a stable dose of antidiabetic drugs (including on Metformin dose between 1000-2000mg) in the past 3 months 5. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
Exclusion criteria
1. Known allergies or contraindication to the contents of the IP, dapagliflozin or saxagliptin tablets. 2. Active participation in another clinical study with IP and/or investigational device 3. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding. 4. Type 1 diabetes mellitus. 5. Treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors at Visit 1 or 2 6. Patients with moderate to severe renal impairment (eGFR persistently \<45 mL/min/1.73 m2 by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula or end-stage renal disease (ESRD) or 'Unstable or rapidly progressing renal disease 7. Patients with severe hepatic impairment (Child-Pugh class C) 8. History of pancreatitis or pancreatic surgery 9. Patients with a history of any malignancy 10. Patients with any of the following CV/Vascular Diseases within 3 months prior to signing the consent at enrolment, as assessed by the investigator: * Myocardial infarction. * Cardiac surgery or revascularization (CABG/PTCA). * Unstable angina. * Transient ischemic attack (TIA) or significant cerebrovascular disease. * Unstable or previously undiagnosed arrhythmia. 11. History of heart failure 12. Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg at any visit up to randomisation 13. History of diabetic ketoacidosis 14. Any acute/chronic systemic infections 15. Recurrent urogenital infections 16. Patients at risk for volume depletion as judged by the investigator 17. Any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient or patient suspected or with confirmed poor protocol or medication compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Abnormalities in Physical Examinations | Enrolment (Week -1) to End of Study (Week 26) | The number of participants with clinically significant abnormalities in physical examinations. |
| Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest | Baseline to End of Study (Week 26) | Adverse events (AEs) including serious adverse events (SAEs), AEs leading to discontinuation (DAE), and adverse events of special interest (volume depletion, renal events, major hypoglycemic events, fractures, urinary/genital tract infections diabetic ketoacidosis, amputations and hospitalization for heart failure) |
| Clinically Important or Significant Abnormalities in Safety Laboratory Values | Enrolment (Week -1) to End of Study (Week 26) | Clinical laboratory results were presented separately for haematology, clinical chemistry, and urinalysis variables. The number of participants with clinically important (haematology and clinical chemistry) or clinically significant (urinalysis) abnormalities in safety laboratory values are presented. |
| Clinically Important Abnormalities in ECG Values | Time Frame: Baseline to End of Study (Week 26) | The number of participants with clinically important abnormalities in ECG values are presented. |
| Clinically Important Abnormalities in Vital Signs (Pulse and Blood Pressure) | Enrolment (Week -1) to End of Study (Week 26) | The number of participants with clinically important abnormalities in vital signs (pulse and blood pressure). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Change at Week 24 Compared to Baseline | Baseline to Week 24 | The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring weight change at week 24 compared to baseline. |
| Systolic Blood Pressure Change at Week 24 Compared to Baseline | Baseline to Week 24 | The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring systolic blood pressure change at week 24 compared to baseline. |
| Fasting Plasma Glucose Change at Week 24 Compared to Baseline | Baseline to Week 24 | The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring fasting plasma glucose change at week 24 compared to baseline. |
| Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline | Baseline to Week 24 | The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring HbA1c change at week 24 compared to baseline. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mgOverall All participants were given once daily fixed dose combination of Dapagliflozin 10 mg / Saxagliptin 5 mg administered orally at the same time of the day throughout the study. | 196 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discontinuation of the study | 14 |
| Overall Study | High plasma glucose-fasting and HbA1c; investigator decision to withdraw participant | 1 |
| Overall Study | Withdrawal of Informed Consent | 8 |
Baseline characteristics
| Characteristic | Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mgOverall |
|---|---|
| Age, Continuous | 52.2 Years STANDARD_DEVIATION 10.27 |
| Body mass index | 28.0 kg/m^2 STANDARD_DEVIATION 4.35 |
| Fasting plasma glucose | 161.8 mg/dL STANDARD_DEVIATION 52.3 |
| Glycated haemoglobin | 8.6 percentage of glycated haemoglobin STANDARD_DEVIATION 0.77 |
| Height | 163 centimeters STANDARD_DEVIATION 8.62 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 196 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 120 Participants |
| Systolic blood pressure | 125.7 mmHg STANDARD_DEVIATION 9.27 |
| Waist circumference | 97.5 centimeters STANDARD_DEVIATION 12.76 |
| Weight | 74.2 kilograms STANDARD_DEVIATION 12.59 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 196 |
| other Total, other adverse events | 22 / 196 |
| serious Total, serious adverse events | 0 / 196 |
Outcome results
Primary
Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest
Adverse events (AEs) including serious adverse events (SAEs), AEs leading to discontinuation (DAE), and adverse events of special interest (volume depletion, renal events, major hypoglycemic events, fractures, urinary/genital tract infections diabetic ketoacidosis, amputations and hospitalization for heart failure)
Time frame: Baseline to End of Study (Week 26)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest | AEs | 40 events |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest | SAEs | 0 events |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest | DAEs | 0 events |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest | Adverse events of special interest | 4 events |
Primary
Clinically Important Abnormalities in ECG Values
The number of participants with clinically important abnormalities in ECG values are presented.
Time frame: Time Frame: Baseline to End of Study (Week 26)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Clinically Important Abnormalities in ECG Values | 0 Participants |
Primary
Clinically Important Abnormalities in Vital Signs (Pulse and Blood Pressure)
The number of participants with clinically important abnormalities in vital signs (pulse and blood pressure).
Time frame: Enrolment (Week -1) to End of Study (Week 26)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Clinically Important Abnormalities in Vital Signs (Pulse and Blood Pressure) | 0 Participants |
Primary
Clinically Important or Significant Abnormalities in Safety Laboratory Values
Clinical laboratory results were presented separately for haematology, clinical chemistry, and urinalysis variables. The number of participants with clinically important (haematology and clinical chemistry) or clinically significant (urinalysis) abnormalities in safety laboratory values are presented.
Time frame: Enrolment (Week -1) to End of Study (Week 26)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Clinically Important or Significant Abnormalities in Safety Laboratory Values | 0 Participants |
Primary
Clinically Significant Abnormalities in Physical Examinations
The number of participants with clinically significant abnormalities in physical examinations.
Time frame: Enrolment (Week -1) to End of Study (Week 26)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Clinically Significant Abnormalities in Physical Examinations | 0 Participants |
Secondary
Fasting Plasma Glucose Change at Week 24 Compared to Baseline
The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring fasting plasma glucose change at week 24 compared to baseline.
Time frame: Baseline to Week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Fasting Plasma Glucose Change at Week 24 Compared to Baseline | Baseline (Visit 2) | 161.8 mg/dL | Standard Deviation 52.3 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Fasting Plasma Glucose Change at Week 24 Compared to Baseline | Week 24 | 136.7 mg/dL | Standard Deviation 41.98 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Fasting Plasma Glucose Change at Week 24 Compared to Baseline | Change from Baseline | -24.4 mg/dL | Standard Deviation 62.89 |
Comparison: Change from baselinep-value: <0.000195% CI: [-33.4, -15.4]Paired t-test test
Secondary
Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline
The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring HbA1c change at week 24 compared to baseline.
Time frame: Baseline to Week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline | Baseline (Visit 2) | 8.6 percentage of glycated haemoglobin | Standard Deviation 0.77 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline | Week 24 | 7.4 percentage of glycated haemoglobin | Standard Deviation 0.98 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline | Change from Baseline | -1.2 percentage of glycated haemoglobin | Standard Deviation 1.09 |
Comparison: Change from baselinep-value: <0.000195% CI: [-1.34, -1.03]Paired t-test test
Secondary
Systolic Blood Pressure Change at Week 24 Compared to Baseline
The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring systolic blood pressure change at week 24 compared to baseline.
Time frame: Baseline to Week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Systolic Blood Pressure Change at Week 24 Compared to Baseline | Baseline (Visit 2) | 125.7 mmHg | Standard Deviation 9.27 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Systolic Blood Pressure Change at Week 24 Compared to Baseline | Week 24 | 124.5 mmHg | Standard Deviation 10.33 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Systolic Blood Pressure Change at Week 24 Compared to Baseline | Change from Baseline | -0.2 mmHg | Standard Deviation 12.9 |
Comparison: Change from baselinep-value: 0.841695% CI: [-2.34, 1.91]Paired t-test test
Secondary
Weight Change at Week 24 Compared to Baseline
The efficacy of the fixed dose combination of dapagliflozin + saxagliptin in Indian Type 2 Diabetes Mellitus participants was analyzed by measuring weight change at week 24 compared to baseline.
Time frame: Baseline to Week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Weight Change at Week 24 Compared to Baseline | Baseline (Visit 2) | 74.2 kilograms | Standard Deviation 12.59 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Weight Change at Week 24 Compared to Baseline | Week 24 | 72.2 kilograms | Standard Deviation 11.51 |
| Fixed Dose Combination of Dapagliflozin 10 mg / Saxagliptin 5 mg | Weight Change at Week 24 Compared to Baseline | Change from Baseline | -2.1 kilograms | Standard Deviation 3.98 |
Comparison: Change from baselinep-value: <0.000195% CI: [-2.66, -1.51]Paired t-test test