Cohort Study of Pioglitazone and Cancer Incidence in Participants With Diabetes Mellitus.

Completed

• Conditions: Diabetes Mellitus, Type 2, Cancer
• Interventions: Drug: Pioglitazone

• Registration Number: NCT02958956
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study was to evaluate whether treatment with pioglitazone is associated with risk of incident cancer at the 10 most common sites in a cohort of participants with recognized diabetes.

Detailed Description

The study enroll a large population of approximately 252467 participants. The study would analyze association of cancer and pioglitazone in 2 cohorts based on the usage of pioglitazone. Participants in were originally planned to be followed-up from January 1, 1997 to December 31, 2005. Based on the discussion with advisory board, it was recommended to increase the study population and duration of follow-up. The follow-up period was extended to June 30, 2012 for the study.

This multi-center trial was conducted in the United States of America. The overall time to participate in this study was approximately 15.5 years. Participants were followed-up from January 1, 1997 up to June 30, 2012 for the assessment of cancer risk associated with pioglitazone use.

Study Timeline

• Study Start: 1997-01-01
• Primary Completion: 2015-05-29
• Study Completion: 2015-05-29
• Study First Submitted: 2016-11-04
• Study First Submitted QC: 2016-11-04
• Study First Posted: 2016-11-08
• Results First Submitted: 2016-11-12
• Results First Submitted QC: 2016-11-12
• Results First Posted: 2017-01-10
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-06
• Last Update Posted: 2018-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 236507

Inclusion Criteria

1. has been in the KPNC diabetes registry Diabetes Mellitus (DM) registry, aged 40 years or older and are members of KPNC as of January 1, 1997, or
2. has been in the DM registry, reached aged 40 years between January 1, 1997 and June 30, 2005 and are KPNC members on their 40th birthday, or
3. has joined KPNC after January 1, 1997, aged 40 years or older when they are identified by the DM registry between January 1, 1997 and June 30, 2005.

Exclusion Criteria

1. Age less than (<) 40 years during study period. 2. No KPNC medication benefits at the time of entry into the cohort (baseline) or gap in medication benefit greater than equal to (>=) 4 months that started in the first 4 months after entering in the cohort.

2. Gap in KPNC membership >= 4 months that started in the first 4 months after entering in the cohort.

3. Participant with a diagnosis of Human immunodeficiency virus (HIV). 5. Participants with evidence of selected surgeries for some cancer sites. 6. All prevalent cancers at baseline, that is, all participants ever diagnosed with cancer other than non-melanoma skin cancer.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ever User of Pioglitazone	Pioglitazone	Ever user of pioglitazone was defined as having filled 2 prescriptions for the drug within a 6-month period.

Primary Outcome Measures

Name	Time	Method
Hazard Ratio of the 10 Most Common Cancers Associated With Ever Use of Pioglitazone	15 years 5 months	The hazard ratio of the 10 most common cancers: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with ever use of pioglitazone. Cox proportional hazards regression modeling was used to provide point and interval estimates of the relative hazard of the 10 most common cancers associated with ever use of pioglitazone. In all regression analyses, these measures of exposure to pioglitazone were treated as time-dependent covariates and time since entry into the cohort was the time scale.
Number of 10 Most Common Cancers Associated Cases	15 years 5 months	Number of 10 most common cancer cases are reported in this measure: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma.

Secondary Outcome Measures

Name	Time	Method
Hazard Ratio of the 10 Most Common Cancers Associated With Time Since First Use of Pioglitazone	15 years 5 months	The hazard ratio of the 10 most common cancers: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with time since first use of pioglitazone. The various times since initiation include \<12 months ago, 12-23 months ago, 24-35 months ago, 36-47 months ago, 48-83 months ago and 84+ months ago. Cox proportional hazards regression modeling was used to provide point and interval estimates of the time since first use. In all regression analyses, these measures of exposure to pioglitazone were treated as time-dependent covariates and time since entry into the cohort was the time scale.
Number of 10 Most Common Cancer Cases By Dose of Pioglitazone	15 years 5 months	The 10 most common cancer cases included: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with dose of pioglitazone. The various doses include 1-9000 mg, 9001-25000 mg, 25001-50000 mg and \>=50001 mg.
Hazard Ratio of the 10 Most Common Cancers Associated With Duration of Pioglitazone	15 years 5 months	The hazard ratio of the 10 most common cancers: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with duration of pioglitazone. The duration of pioglitazone was categorized as \<12 months, 12-23 months, 24-35 months, 36-59 months, 60+ months. Cox proportional hazards regression modeling was used to provide point and interval estimates of the cumulative duration. In all regression analyses, these measures of exposure to pioglitazone were treated as time-dependent covariates and time since entry into the cohort was the time scale.
Number of 10 Most Common Cancers Cases by Time Since First Use of Pioglitazone	15 years 5 months	Number of 10 most common cancer cases: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with time since first use of pioglitazone. Time since initiation of pioglitazone was categorized as \<12 months ago, 12-23 months ago, 24-35 months ago, 36-47 months ago, 48-83 months ago and 84+ months ago.
Number of 10 Most Common Cancer Cases by Duration of Pioglitazone	15 years 5 months	The 10 most common cancer cases included: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with duration of pioglitazone. The duration of pioglitazone was categorized as \<12 months, 12-23 months, 24-35 months, 36-59 months, 60+ months.
Hazard Ratio of the 10 Most Common Cancers Associated With Cumulative Dose of Pioglitazone	15 years 5 months	The hazard ratio of the 10 most common cancers: prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectal, and melanoma associated with dose of pioglitazone. The various doses include 1-9000 mg, 9001-25000 mg, 25001-50000 milligram (mg) and greater than or equal to (\>=) 50001 mg. Cox proportional hazards regression modeling was used to provide point and interval estimates of the dose. In all regression analyses, these measures of exposure to pioglitazone were treated as time-dependent covariates and time since entry into the cohort was the time scale.