Forxiga (Dapagliflozin) Regulatory Postmarketing Surveillance

Protocol Title: Forxiga (dapagliflozin) Regulatory Postmarketing Surveillance

Department: Korea Medical

Objective(s): The primary objective of this study is to examine the safety profiles of Forxiga in Korean patients with T2DM.

The secondary objective of this study is to examine the effectiveness profiles of Forxiga in Korean patient with T2DM.

The exploratory objective of this study is to identify factors that might be associated with the safety and effectiveness profiles of Forxiga in Korean patient with T2DM.

Study Design: This is a local, prospective, noninterventional, regulatory postmarketing surveillance study. Adult patients with type 2 diabetes mellitus who are initiating Forxiga as indicated by the Ministry of Food and Drug Safety (MFDS) will be included. Patients will be followed for a minimum of 12 weeks or a minimum 24 weeks. Patients will be treated as part of routine practice at Korean healthcare centers by accredited physicians. In this study, patients will receive 10 mg or 5 mg of Forxiga in conjunction with diet and exercise modifications for the treatment of T2DM.

Study Population: Physicians should enroll adult patients who are diagnosed with T2DM and who initiate treatment with 10 mg of Forxiga, or 5 mg of Forxiga in patients with severe hepatic impairment as a starting dose, for the first time.

Data Collection Methods: and Astra-Zeneca will select medical institutions including relevant departments, such as internal medicine and family medicine, of university hospitals, general hospitals and clinics where the surveillance drug is mainly prescribed and where staff can sufficiently fulfill the objectives of the surveillance and request for surveillance after signing a written contract. Patients' medical records will be data sources in this study. Only if the laboratory test is done as part of standard of care practice and the data are available will the data be collected for this study.

Data Analyses: Statistical analyses will be of explorative and descriptive nature. All analyses will be performed for the total study population who will consist of all patients taking at least one dose of Forxiga. For the safety assessment, occurrences of adverse events (AEs), serious adverse events, adverse drug reactions (ADR), and unexpected adverse drug reactions will be calculated. Severity, actions taken to the surveillance drug, outcome, and causal relationship of AE to the study drug will be analyzed. At the time of the regular reporting and the final reporting, the event count, incidence proportion (that is, the number of patients with any events divided by the number of patients) and incidence rate (number of patients with any events divided by the duration of time patients are followed up in the study) of all the adverse events surveyed during the re-examination period will be summarized, and 95% confidence interval will be presented. Changes in Hemoglobin A1c(HbA1c), Fasting plasma glucose(FPG), and Post-prandial glucose-2 hour(2-hr PPG) before and after administration of Forxiga will be analyzed. At the time of the regular reporting and the final reporting, the event count and effectiveness rate of improvement of lab result (HbA1c, FPG, and PPG), surveyed during the re-examination period will be summarized, and 95% confidence interval will be presented. In order to explore the factors that might influence safety and effectiveness profiles, the cumulative incidence proportion of adverse events and effectiveness rate will be analyzed by patients' background characteristics Sample Size/Power: In accordance with the guidelines provided by the MFDS, at least 3,000 patients will be enrolled. For the overall study population of approximately 3000 patients, the incidence proportion of infrequent adverse events(for example, an incidence proportion of 0.1%) can be estimated with a 95% CI of (0.02, 0.29) (n=3 patients with events).

Limitations/Strengths: The surveillance, with characteristics of a noninterventional, observation study, has no control group and will follow patients in usual clinical practice. Given these conditions, the types of safety and effectiveness data available for collection may be limited compared with other noninterventional clinical trials. This surveillance study will generate results from a wider range of data than those previously derived from the more limited clinical trial setting and will allow for longer follow up among a more varied patient population.