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

This study has been completed.
Sponsor:
Collaborators:
Kaiser Permanente
Department of Epidemiology at University of Pennsylvania
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01637935
First received: July 7, 2012
Last updated: December 9, 2015
Last verified: December 2015
  Purpose
To assess the potential association between pioglitazone and bladder cancer compared with non-pioglitazone users among patients with type 2 diabetes mellitus.

Condition Intervention
Diabetes
Bladder Cancer
Drug: Pioglitazone

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cohort Study of Pioglitazone and Bladder Cancer in Patients With Diabetes

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Incident Diagnosis of Bladder Cancer (10-year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ] [ Designated as safety issue: Yes ]
    Incident bladder cancers were identified from January 1, 1997 to December 31, 2012.


Secondary Outcome Measures:
  • Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ] [ Designated as safety issue: Yes ]
  • Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ] [ Designated as safety issue: Yes ]
  • Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ] [ Designated as safety issue: Yes ]
  • Stage of Bladder Cancer (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ] [ Designated as safety issue: Yes ]

Enrollment: 193099
Study Start Date: July 2004
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Name: 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.

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

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01637935     History of Changes
Other Study ID Numbers: 01-03-TL-OPI-524  U1111-1132-3482 
Study First Received: July 7, 2012
Results First Received: August 31, 2012
Last Updated: December 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Urinary Bladder Neoplasms
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016