Diabetes Mellitus, Type 2, CancerNCT02958956

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

An observational study of Diabetes Mellitus, Type 2, Cancer, run by Takeda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Diabetes Mellitus, Type 2, Cancer
What is being tested?: Pioglitazone
How many people: 236,507 participants
Where: No sites listed yet
Study dates: 1 Jan 1997to 29 May 2015
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Participants with a historical diagnosis of Type 2 diabetes mellitus (T2DM) with pioglitazone exposure identified from the Kaiser Permanente of Northern California(KPNC) Diabetes Registry (with or without diabetes) and had completed Member Health Survey (MHS) were enrolled in the epidemiology study.

Who may be able to join

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

Who cannot join

None listed.

About this study

Official title: Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes Mellitus

Read the 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.

Conditions: Diabetes Mellitus, Type 2, Cancer
Being tested: Pioglitazone
Keywords: Drug Therapy
Medical subject headings: Diabetes Mellitus, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PioglitazoneDrug
Participants with diabetes who were members of the KPNC registry, and had received at least 2 prescriptions for pioglitazone within a 6-month period were followed up to 15.5 years (1997-2012) in this observational study 1.

Study groups in NCT02958956
Study group	Role	What they receive
Ever User of Pioglitazone		Ever user of pioglitazone was defined as having filled 2 prescriptions for the drug within a 6-month period. Receives: Drug: Pioglitazone
Never User of Pioglitazone		Never user of pioglitazone, which included participants receiving no diabetes medications, with fewer than 2 pioglitazone prescription fills in a 6-month period, and with use of diabetes medications other than pioglitazone.

What is being measured

The primary outcome is the main question the study is designed to answer.

Hazard Ratio of the 10 Most Common Cancers Associated With Ever Use of Pioglitazone
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.
Measured: 15 years 5 months
Number of 10 Most Common Cancers Associated Cases
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.
Measured: 15 years 5 months

Secondary outcomes (6)

Hazard Ratio of the 10 Most Common Cancers Associated With Time Since First Use of Pioglitazone
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.
Measured: 15 years 5 months
Number of 10 Most Common Cancers Cases by Time Since First Use of Pioglitazone
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.
Measured: 15 years 5 months
Hazard Ratio of the 10 Most Common Cancers Associated With Duration of Pioglitazone
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.
Measured: 15 years 5 months
Number of 10 Most Common Cancer Cases by Duration of Pioglitazone
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.
Measured: 15 years 5 months
Hazard Ratio of the 10 Most Common Cancers Associated With Cumulative Dose of Pioglitazone
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.
Measured: 15 years 5 months
Number of 10 Most Common Cancer Cases By Dose of Pioglitazone
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.
Measured: 15 years 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 199729 May 2015

First posted8 Nov 2016 (estimated)
Study start1 Jan 1997
Primary completion29 May 2015
Study completion29 May 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Diabetes Mellitus, Type 2, CancerStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 236,507 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02958956
Sponsor's protocol ID: AD-4833_403A
Other IDs: EUPAS10335
Status last verified: Feb 2018
First submitted: 4 Nov 2016
Last updated: 7 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Diabetes Mellitus, Type 2, Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes Mellitus
ClinicalTrials.gov ID: NCT02958956
Acronym / sponsor ID: AD-4833_403A
Conditions: Diabetes Mellitus, Type 2, Cancer
Keywords: Drug Therapy
Study type: Observational
Recruitment status: Completed
Enrolment: 236,507 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 1 Jan 1997 (actual)
Primary completion: 29 May 2015 (actual)
Study completion: 29 May 2015 (actual)
First posted: 8 Nov 2016 (estimated)
Results: Posted 10 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Ever User of Pioglitazone	–	Drug: PioglitazoneEver user of pioglitazone was defined as having filled 2 prescriptions for the drug within a 6-month period.
Never User of Pioglitazone	–	–Never user of pioglitazone, which included participants receiving no diabetes medications, with fewer than 2 pioglitazone prescription fills in a 6-month period, and with use of diabetes medications other than pioglitazone.

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Participants with a historical diagnosis of Type 2 diabetes mellitus (T2DM) with pioglitazone exposure identified from the Kaiser Permanente of Northern California(KPNC) Diabetes Registry (with or without diabetes) and had completed Member Health Survey (MHS) were enrolled in the epidemiology study.

Key inclusion criteria (6 listed)

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

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PioglitazoneParticipants with diabetes who were members of the KPNC registry, and had received at least 2 prescriptions for pioglitazone within a 6-month period were followed up to 15.5 years (1997-2012) in this observational study 1.	Drug	Ever User of Pioglitazone

Primary outcome

Hazard Ratio of the 10 Most Common Cancers Associated With Ever Use of Pioglitazone
Time frame: 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
Time frame: 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.

6 secondary outcomes

Hazard Ratio of the 10 Most Common Cancers Associated With Time Since First Use of Pioglitazone
Time frame: 15 years 5 months
Number of 10 Most Common Cancers Cases by Time Since First Use of Pioglitazone
Time frame: 15 years 5 months
Hazard Ratio of the 10 Most Common Cancers Associated With Duration of Pioglitazone
Time frame: 15 years 5 months
Number of 10 Most Common Cancer Cases by Duration of Pioglitazone
Time frame: 15 years 5 months
Hazard Ratio of the 10 Most Common Cancers Associated With Cumulative Dose of Pioglitazone
Time frame: 15 years 5 months
Number of 10 Most Common Cancer Cases By Dose of Pioglitazone
Time frame: 15 years 5 months

Results and safety

Results posted to the registry on 10 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ever User of Pioglitazone	38,190	38,190
Never User of Pioglitazone	198,317	198,317

Primary outcome: Hazard Ratio of the 10 Most Common Cancers Associated With Ever Use of Pioglitazone

Time frame: 15 years 5 months. Number (95% Confidence Interval). Unit: Ratio

Measure	Full Cohort n = 236507
Prostate	1.13 (1.02 to 1.26)
Breast	1.00 (0.88 to 1.13)
Lung/Bronchus	1.00 (0.87 to 1.15)
Colon	0.91 (0.78 to 1.05)
Non-Hodgkin Lymphoma	1.00 (0.81 to 1.23)
Corpus Uteri	0.88 (0.71 to 1.09)
Pancreatic	1.41 (1.16 to 1.71)
Kidney/Renal Pelvis	0.95 (0.76 to 1.18)

Population analysed: Analysis population included T2DM participants who were identified from the KPNC Diabetes Registry in the study 1.

Primary outcome: Number of 10 Most Common Cancers Associated Cases

Time frame: 15 years 5 months. Number. Unit: Cases

Measure	Ever User of Pioglitazone n = 38190	Never User of Pioglitazone n = 198317
Prostate	476	3307
Breast	320	2478
Lung/Bronchus	282	2300
Colon	233	1844
Non-Hodgkin Lymphoma	120	839
Corpus Uteri	118	799
Pancreatic	164	648
Kidney/Renal Pelvis	110	690

Population analysed: Analysis population included T2DM participants who were identified from the KPNC Diabetes Registry in the study 1.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ever User of Pioglitazone	0 of 0	0 of 0	Not reported
Never User of Pioglitazone	0 of 0	0 of 0	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus, Type 2, Cancer, run by Takeda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hazard Ratio of the 10 Most Common Cancers Associated With Ever Use of Pioglitazone (time frame: 15 years 5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02958956.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2018.