Clinical trial NCT02695121: Cancer in Patients on Dapagliflozin and Other Antidiabetic Treatment
Official title: Comparison of the Risk of Cancer Between Patients With Type 2 Diabetes Exposed to Dapagliflozin and Those Exposed to Other Antidiabetic Treatments
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Bladder Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-03-01
Enrollment: 2133575
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible patients must meet all of the inclusion criteria and none of the exclusion criteria. Comparator patients will be randomly selected in a 4:1 ratio to the dapagliflozin patients.

Brief summary: The primary objectives of this study are (1) to compare the incidence of breast cancer, by insulin use at cohort entry, among females with type 2 diabetes who are new users of dapagliflozin and females who are new users of antidiabetic drugs (ADs) in classes other than sodium-glucose cotransporter 2 (SGLT2) inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy and (2) to compare the incidence of bladder cancer, by insulin use at the index date and by pioglitazone use at the index date, among male and female patients with type 2 diabetes who are new users of dapagliflozin and those who are new users of ADs in classes other than SGLT2 inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy. Secondary objectives will compare, by insulin use at cohort entry, frequency of several measures of health care use, baseline characteristics, and incidence of selected other cancers in males and females between the two exposure cohorts.

Detailed description: This is a multinational cohort database study to estimate the incidence of female breast cancer and bladder cancer, by insulin use at cohort entry, in patients who are prescribed dapagliflozin compared to patients prescribed other specific oral antidiabetic drugs. Dapagliflozin and other antidiabetic drugs are used to treat type 2 diabetes mellitus. Because of the mechanism of action for dapagliflozin and results from small safety monitoring studies, there is interest in further evaluating the safety of dapagliflozin in a large populations.

The study will be implemented in four administrative health care data sources in three countries: in the United Kingdom, the Clinical Practice Research Datalink (CPRD); in the United States, the Centers for Medicare and Medicaid Services (CMS) Medicare databases and the HealthCore Integrated Research Database (HIRDSM); and, in the Netherlands, the PHARMO Database Network. Individuals in the databases will be included in the study if they meet the following age criteria; 40 years or older (CPRD and PHARMO), 40 to 64 years (HIRD) or 65 years or older (Medicare); and if they did not have type 1 diabetes, were treated with one of the study drugs and meet the criteria of at least 180 days of electronic data before their first prescription of the study drug. The study period starts November 13, 2012 in CPRD, November 1, 2013 in PHARMO and January 9, 2014 in the United States data sources, and will end at the latest available data at each database at the time of analysis

Eligibility criteria: Inclusion Criteria:

1. patient was newly prescribed dapagliflozin or newly prescribed an AD (with or without other ADs) in a class other than SGLT2 inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy on the prescription index date
2. patient is aged 40 years or older at cohort entry; and
3. patient was enrolled in the data source for at least 180 days before the prescription index date.

Exclusion Criteria:

1. any evidence of diagnosis of type 1 diabetes before cohort entry or use of insulin alone as the first recorded AD;
2. any diagnosis of cancer before cohort entry (other than nonmelanoma skin cancer);
3. any recording of hematuria before cohort entry;
4. any cystoscopy or urine cytology performed before cohort entry;
5. any breast biopsy performed before cohort entry.

Primary outcomes:
measure: Incidence of breast cancer
timeFrame: Index day up to twelve years
measure: Incidence of bladder cancer
timeFrame: Index day up to twelve years
Secondary outcomes:
measure: Incidence of compsite cancer outcomes
timeFrame: Index day up to twelve years
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Research Site
state: Delaware
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Utrecht
country: Netherlands
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: RTI Health Solutions
name: Lia Gutierrez
role: PRINCIPAL_INVESTIGATOR
References: