Post-authorisation safety study to assess the risk of urinary tract malignancies in relation to empagliflozin exposure in patients with type 2 diabetes: a multi-database European study (PASS DiabCancer)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/48643
• EU PAS number:
  EUPAS16424
• Study ID:
  48643
• Official title and acronym:
  Post-authorisation safety study to assess the risk of urinary tract malignancies in relation to empagliflozin exposure in patients with type 2 diabetes: a multi-database European study (PASS DiabCancer)
• DARWIN EU® study:
  No
• Study countries:
  Finland

  Sweden

  United Kingdom
• Study description:
  Jardiance (empagliflozin), a highly potent and selective inhibitor of the sodium-glucose cotransporter 2 (SGLT-2), was approved in Europe in May 2014 for the treatment of type 2 diabetes mellitus (T2D) to improve glycaemic control in adults. Synjardy (empagliflozin/metformin HCl) was approved in Europe in May 2015. As part of the risk management plan, Boehringer Ingelheim International GmbH (BI) has committed to conduct a post-authorisation safety study (PASS) to evaluate safety of empagliflozin regarding urinary tract malignancies in incident users of empagliflozin compared to incident users of dieptidyl peptidase-4 (DPP-4) inhibitors and incident users of SGLT-2 inhibitors. The inclusion of renal cancer as a potential risk was based on preclinical toxicology findings and clinical cases of bladder cancer observed with other SGLT-2 inhibitors. This PASS will be conducted using routinely collected health information from the UK, Finland, and Sweden, through an observational cohort study among adult patients with type 2 diabetes mellitus and at least 12 months of continuous enrollment in the UK CPRD, Finland or Swedish national registries. New users of empagliflozin will be compared to new users of dipeptidyl peptidase-4 (DPP-4) inhibitors and to new users of other SGLT-2 inhibitors. Estimations will be made on the crude and adjusted incidence rates and adjusted incidence rate ratios of the primary and secondary outcomes. Primary outcomes are urinary tract cancers, bladder cancer, and renal cancer. Secondary outcomes include non-renal, non-bladder urinary tract cancers.
• Study status:
  Ongoing

Research institutions and networks

Institutions

IQVIA

United Kingdom

Study timelines

Date when funding contract was signed

Actual: 05/04/2016

Study start date

Planned: 15/11/2016

Actual: 16/11/2016

Data analysis start date

Planned: 01/12/2020

Date of interim report, if expected

Planned: 31/03/2021

Actual: 13/03/2017

Date of final study report

Planned: 30/04/2024

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Boehringer Ingelheim International GmbH

Study protocol

Initial protocol

ER-9521_protocol_1245-0097_version3

Updated protocol

1245-0097 Final protocol v8.0_Redacted.pdf

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 3 (required)