Cohort Study of Pioglitazone and Bladder Cancer in Patients With Type II Diabetes

Study Overview
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Brief Summary
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To assess the potential association between pioglitazone and bladder cancer compared with non-pioglitazone users among patients with type 2 diabetes mellitus.

Detailed Description
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Following guidance from the United States Food and Drug Administration (FDA) and European Medicines Agency, the University of Pennsylvania and Kaiser Permanente Northern California (KPNC) designed and conducted this study using the KPNC database to assess the potential association between pioglitazone and bladder cancer among patients with type 2 diabetes mellitus. The study was conducted over the course of 10 years, with a series of interim analyses undertaken during this period and provided to the sponsor (Takeda) and the appropriate regulatory agencies. In 2011, the planned 5-year interim analysis of this study was published in Diabetes Care. That report included data from 1 January 1997 to 30 April 2008. Following reporting of these data, there was a request from the FDA for an additional fourth interim analysis at 8 years including data from 1 January 1997 to 31 December 2010. In August 2011 the FDA requested inclusion of a sensitivity analysis to assess change of cohort entry criteria to minimize left censoring of exposure. Included in the FDA request was a duration analysis for other antidiabetic medications. In August 2014, the final 10-year analyses were completed and submitted to the sponsor and regulatory agencies. Interim results previously posted on clinicaltrials.gov are available in the public archive

Official Title
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Cohort Study of Pioglitazone and Bladder Cancer in Patients With Diabetes

Conditions
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Diabetes, Bladder Cancer

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study cohort included both patients with an established diagnosis of diabetes mellitus prior to January 1, 1997 and those who were newly diagnosed prior to December 31, 2002. Patients were eligible for the study cohort if they met any of the following criteria: As of January 1, 1997 they had been diagnosed with diabetes mellitus, were age 40 or older and were members of KPNC, They had been diagnosed with diabetes mellitus, reached age 40 between January 1, 1997 and December 31, 2002 and were KPNC members on their 40th birthday, or Had diabetes mellitus and were age 40 or older when they joined KPNC between January 1, 1997 and December 31, 2002. Exclusion Criteria: Diagnosis of bladder cancer recorded in the KPNC cancer registry prior to entry to the cohort or within 6 months of entry into KPNC.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pioglitazone exposed group<br>Defined as those patients having filled at least two prescriptions for pioglitazone within a 6-month period. Patients in the pioglitazone group may also have exposure to other diabetic medications | Drug: Pioglitazone<br>* Pioglitazone tablets.<br>* Other names: Actos;|
| Pioglitazone unexposed group<br>Defined as patients who did not fill at least two prescriptions for pioglitazone within a 6-month period. Patients in the pioglitazone unexposed group may have been exposed to other diabetic medications. This group also included diabetic patients without any diabetic medications. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident Diagnosis of Bladder Cancer (10-year Analysis) | Incident bladder cancers were identified from January 1, 1997 to December 31, 2012. | January 1, 1997 to December 31, 2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis) |  | January 1, 1997 to December 31, 2012 | 
| Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis) |  | January 1, 1997 to December 31, 2012 | 
| Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis) |  | January 1, 1997 to December 31, 2012 | 
| Stage of Bladder Cancer (10 Year Analysis) |  | January 1, 1997 to December 31, 2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy