Clinical trial NCT04445714: To Assess Safety of Fixed Dose Combination of Dapagliflozin and Saxagliptin in Type 2 Diabetes Mellitus Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-06-24
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events (AEs) Including Serious Adverse Events (SAEs), AEs Leading to Discontinuation (DAE), and Adverse Events of Special Interest
timeFrame: Baseline to End of Study (Week 26)
measure: Clinically Important or Significant Abnormalities in Safety Laboratory Values
timeFrame: Enrolment (Week -1) to End of Study (Week 26)
measure: Clinically Important Abnormalities in ECG Values
timeFrame: Time Frame: Baseline to End of Study (Week 26)
measure: Clinically Important Abnormalities in Vital Signs (Pulse and Blood Pressure)
timeFrame: Enrolment (Week -1) to End of Study (Week 26)
measure: Clinically Significant Abnormalities in Physical Examinations
timeFrame: Enrolment (Week -1) to End of Study (Week 26)
Secondary outcomes:
measure: Glycated Haemoglobin (HbA1c) Change at Week 24 Compared to Baseline
timeFrame: Baseline to Week 24
measure: Weight Change at Week 24 Compared to Baseline
timeFrame: Baseline to Week 24
measure: Systolic Blood Pressure Change at Week 24 Compared to Baseline
timeFrame: Baseline to Week 24
measure: Fasting Plasma Glucose Change at Week 24 Compared to Baseline
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Bangalore
country: India
facility: Research Site
city: Bhubaneswar
country: India
facility: Research Site
city: Chandigarh
country: India
facility: Research Site
city: Coimbatore
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Lucknow
country: India
facility: Research Site
city: Mohali
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Dr Anil Bhansali
role: PRINCIPAL_INVESTIGATOR
affiliation: Fortis Hospital Mohali
name: Dr K P Singh
role: PRINCIPAL_INVESTIGATOR
affiliation: Sparsh Hospitals & Critical Care (P) Ltd, Bhubaneswar
name: Dr Indira Pattnaik
role: PRINCIPAL_INVESTIGATOR
affiliation: M V Hospital &Research centre Lucknow
name: Dr Sandeep Kumar Gupta
role: PRINCIPAL_INVESTIGATOR
affiliation: Thumbay Hospital New Life Hyderabad
name: Dr Faraz Farishta
role: PRINCIPAL_INVESTIGATOR
affiliation: KG Hospital
name: Dr Girithara Jayaram Naidu
role: PRINCIPAL_INVESTIGATOR
References: