Status: Ongoing
First registered on:
17/10/2019
Last updated on:
20/04/2023
1. Study identification
EU PAS Register NumberEUPAS31718
Official titlePost-authorization safety study to assess the risk of diabetic ketoacidosis among type 2 diabetes mellitus patients treated with ertugliflozin compared to patients treated with other antihyperglycemic agents
Study title acronymMK-8835-062
Study typeObservational study
Brief description of the studyA non-interventional cohort study will be conducted using the Reagan-Udall Foundation for the Food and Drug Administration (FDA)’s Innovation in Medical Evidence and Development Surveillance Distributed Database (IMEDS-DD), a subset of the FDA Sentinel Distributed Database. This study will address the research question of whether new use of ertugliflozin is associated with an increased risk of diabetic ketoacidosis (DKA), compared to new use of other non-sodium–glucose cotransporter 2 (SGLT2) inhibitor antihyperglycemic agents (AHAs) among type 2 diabetes mellitus (T2DM) patients. Propensity score matching will be used for confounding adjustment, followed by Cox proportional hazards models for risk estimation.
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre nameReagan-Udall Foundation for the Food and Drug Administration
Centre locationWashington, DC, U.S.A
Details of (Primary) lead investigator
Title Dr
Last name Toh
First name Sengwee
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed03/07/2018
Start date of data collection24/10/201917/10/2019
Start date of data analysis31/03/2024
Date of interim report, if expected31/12/202109/12/2021
Date of final study report31/10/2024
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesMerck Sharp & Dohme LLC60
Charities
Government body
Research councils
EU funding scheme
OtherPfizer Inc.40
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Merck Sharp & Dohme LLC
First name Clinical Trials Disclosure
Address line 1126 East Lincoln Avenue
Address line 2P.O. Box 2000
Address line 3
CityRahway, N.J.
Postcode07065
CountryUnited States
Phone number (incl. country code)1-7325941816
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Merck Sharp & Dohme LLC
First name Clinical Trials Disclosure
Address line 1126 East Lincoln Avenue
Address line 2P.O. Box 2000
Address line 3
CityRahway, N.J.
Postcode07065
CountryUnited States
Phone number (incl. country code)1-7325941816
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Product NameSTEGLATRO
CountryUnited States
Substance INN(s)ERTUGLIFLOZIN
Product NameSEGLUROMET
CountryUnited States
Substance INN(s)ERTUGLIFLOZIN
Product NameSTEGLUJAN
CountryUnited States
Substance INN(s)ERTUGLIFLOZIN
Product NameSEGLUROMET
CountryUnited States
Substance INN(s)METFORMIN
Product NameSTEGLUJAN
CountryUnited States
Substance INN(s)SITAGLIPTIN
7. Medical conditions to be studied
Medical condition(s)Yes
Diabetic ketoacidosis
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects8819
Additional information
A total of 66 DKA events in ertugliflozin and comparator AHA groups combined is required to detect a hazard ratio of 2.0 for DKA with targeted power of 80% and significance level of 0.05 in a 2-sided test. 8,819 person-years of ertugliflozin new users matched to comparator AHA new users in a 1:1 ratio on propensity score is required, assuming DKA incidence rate is 2.5 per 1,000 person-years.
10. Source of data
Is this study being carried out with an established data source?No
Sources of data
Administrative database, e.g. claims database
Data sources not registered with ENCePP: Innovation in Medical Evidence and Development Surveillance Distributed Database (IMEDS-DD). Administrative database: e.g. claims database.
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
1. To assess the risk of DKA among new users of ertugliflozin relative to new users of sulfonylureas (SUs) or thiazolidinediones (TZDs).
2. To assess the risk of DKA among new users of ertugliflozin relative to new users of incretin-based drugs [i.e. dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists].
Are there primary outcomes?Yes
Hospitalization for DKA identified from principal discharge diagnosis of inpatient claims.
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Follow-up for each new use of a given exposure will begin on the index date until the earliest of hospitalized DKA or any of the following criteria: Discontinuation of the index exposure; Initiation of the opposite exposure; Initiation of other SGLT2 inhibitor(s); Initiation of insulin; Disenrollment from either medical or prescription drug insurance plan; End of data availability; Recorded death.
15. Data analysis plan
Please provide a brief summary of the analysis method
Baseline demographic and clinical characteristics will be described by exposure group before and after propensity score matching. Incidence rates (and 95% confidence interval) of DKA will be calculated by exposure group. The differences between the exposure groups in terms of time to DKA will be assessed using Kaplan-Meier survival curves with log rank test. Cox proportional hazards models will be used separately to compare the risk of DKA among new users of ertugliflozin to that among new users of SU/TZD; and to compare the risk of DKA among new users of ertugliflozin to that among new users of incretin-based drugs. Subgroup analysis will be further conducted by concomitant insulin use on the index date. Sensitivity analyses pre-defined in the protocol will be conducted to assess the robustness of the study results.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
