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

February 6, 2018 updated by: Takeda

Cohort Study of Pioglitazone and Bladder Cancer in Patients With Diabetes

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Observational

Enrollment (Actual)

193099

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study was conducted within Kaiser Permanente Northern California (KPNC), which provides comprehensive healthcare services to approximately 3.2 million members. The source population was identified from the KPNC diabetes registry, which was first constructed in 1993 and has been updated annually since then. The registry identifies patients primarily from four data sources: primary hospital discharge diagnoses of diabetes mellitus (since 1971); two or more outpatient visit diagnoses of diabetes (since 1995); any prescription for a diabetes-related medication (since 1994); or any record of an abnormal hemoglobin A1c (HbA1c) test (>6.7%) (since 1991).

The diabetes registry gathers data from a variety of KPNC electronic medical records (EMR) to build and follow the registry cohort across time. These data include cancer registries, pharmacy records, laboratory records, and inpatient and outpatient medical diagnoses.

Description

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:

    1. As of January 1, 1997 they had been diagnosed with diabetes mellitus, were age 40 or older and were members of KPNC,
    2. 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

    3. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pioglitazone exposed group
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
Pioglitazone tablets.
Other Names:
  • Actos
Pioglitazone unexposed group
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?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Takeda

Collaborators

Kaiser Permanente
Department of Epidemiology at University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (ACTUAL)

August 1, 2014

Study Completion (ACTUAL)

August 1, 2014

Study Registration Dates

First Submitted

July 7, 2012

First Submitted That Met QC Criteria

July 7, 2012

First Posted (ESTIMATE)

July 11, 2012

Study Record Updates

Last Update Posted (ACTUAL)

March 7, 2018

Last Update Submitted That Met QC Criteria

February 6, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-03-TL-OPI-524
  • U1111-1132-3482 (REGISTRY: WHO)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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