To Assess Safety of Fixed Dose Combination of Dapagliflozin and Saxagliptin in Type 2 Diabetes Mellitus Patients

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

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 Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: dapagliflozin and saxagliptin

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.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560017
    • Research Site
  • Bhubaneswar, India, 751007
    • Research Site
  • Chandigarh, India, 160012
    • Research Site
  • Coimbatore, India, 641018
    • Research Site
  • Hyderabad, India, 500024
    • Research Site
  • Kolkata, India, 700020
    • Research Site
  • Lucknow, India, 226003
    • Research Site
  • Mohali, India, 160062
    • Research Site
  • New Delhi, India, 110076
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: dapagliflozin and saxagliptin; Singe arm once daily fixed dose combination of Dapa/Saxa 10 mg/5 mg administered orally	Drug: dapagliflozin and saxagliptin; Combination of dapagliflozin and saxagliptin tablet once daily fixed dose combination of Dapa/Saxa 10 mg/5 mg administered orally; Other Names: QTERN Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline to End of Study (Week 26)
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.	Enrolment (Week -1) to End of Study (Week 26)
Clinically Important Abnormalities in ECG Values	The number of participants with clinically important abnormalities in ECG values are presented.	Time Frame: Baseline to End of Study (Week 26)
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).	Enrolment (Week -1) to End of Study (Week 26)
Clinically Significant Abnormalities in Physical Examinations	The number of participants with clinically significant abnormalities in physical examinations.	Enrolment (Week -1) to End of Study (Week 26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 24
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.	Baseline to Week 24
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.	Baseline to Week 24
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.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Dr K P Singh, Fortis Hospital Mohali; Principal Investigator: Dr Indira Pattnaik, Sparsh Hospitals & Critical Care (P) Ltd, Bhubaneswar; Principal Investigator: Dr Sandeep Kumar Gupta, M V Hospital &Research centre Lucknow; Principal Investigator: Dr Faraz Farishta, Thumbay Hospital New Life Hyderabad; Principal Investigator: Dr Girithara Jayaram Naidu, KG Hospital; Principal Investigator: Dr Anil Bhansali, Post Graduate Institute of Medical Education and Research, Chandigarh

Publications and helpful links

Helpful Links

• CSP redacted
• SAP redacted
• CSR Synopsis redacted

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): March 14, 2023
• Study Completion (Actual): March 14, 2023

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: September 9, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Enzyme Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Saxagliptin
• Other Study ID Numbers: D1683C00013

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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• 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; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No