Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies)NCT01077323

A Retrospective Cohort Study of Acute Pancreatitis in Relation to Use of Exenatide and Other Antidiabetic Agents

An observational study of Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies) and Healthy Subjects (Treated With no Diabetes Therapies), run by AstraZeneca at 1 site in United States.

Completed

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

Official record

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Trial summary

Who is it for?: Any age
Conditions the study is for: Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies), Healthy Subjects (Treated With no Diabetes Therapies)
What is being tested?: exenatide, Other antidiabetic therapies and No diabetes therapy
Type of treatment: Injection or infusion
How many people: 363,766 participants
Where: 1 siteUnited States
Study dates: Sep 2004to Mar 2008
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Study population: This retrospective study utilized medical claims data from a large US health plan affiliated with i3 Drug Safety. The individuals covered by this health plan are geographically diverse across the United States. The health plan provides fully insured coverage for physician, hospital and prescription drug services. The providers of these services submit their claims for payment directly to the health plan. i3 Drug Safety uses de-identified data derived from these claims daily for a wide range of safety, utilization, and economic analyses.

Who may be able to join

Exenatide Initiators: The date of the first dispensing of exenatide under which a potential cohort member might qualify will be 1 June 2005, and the latest date will be 31 December 2007. We will note the first initiation of exenatide, and also note subsequent initiation of other antidiabetic drugs. Eligible exenatide initiators will be included in the exenatide initiator cohort on the first eligible dispensing following at least 9 months of continuous health plan enrollment.
Other Antidiabetic Drug Initiators: The date of the first dispensing of an antidiabetic drug other than exenatide under which a potential cohort member might qualify will be 1 June 2005, and the latest date will be 31 December 2007. We will note the earliest date of other antidiabetic drug dispensings within their cohort membership, and also note subsequent initiation of other antidiabetic drugs. We will choose a subset of this comparator cohort randomly selected to be approximately 9 times larger than the exenatide initiators and will oversample patients receiving certain drugs to the extent necessary to ensure inclusion of at least as many persons initiating these drugs as initiating exenatide. Specifically, oversampling will be performed as needed on initiators of metformin, TZDs, SUs, sitagliptin and insulin glargine to allow for further sub-analysis.
Exenatide and Other Antidiabetic Drug Initiators: For all patients in these two study cohorts, the date of cohort entry (the date ranged between January 1, 2005 and December 31, 2007) marked the beginning of observation for study outcomes (follow-up). The end of observation for a given patient happened on the earliest of occurrence of likely acute pancreatitis, end of the study period (March 31, 2008), or disenrollment from the health plan.
Non-Diabetes Cohort: A third cohort will consist of randomly-selected Ingenix Research Data Mart members who have no claim associated with a diabetes diagnosis or antidiabetic drug dispensing in the baseline continuous enrollment period. This cohort will enter as of the later of 1 June 2005 or completion of 9 months continuous baseline enrollment and will provide follow-up through end of enrollment or 31 March 2008, or the receipt of an antidiabetic drug dispensing or diabetes diagnosis, at which point they may enter one of the other exposure cohorts.

Who cannot join

The 3 cohorts (exenatide initiators, other antidiabetic initiators, and those without diabetes) will be subject to minimal exclusions in order to observe acute pancreatitis across a wide spectrum of patient characteristics. We will apply a baseline enrollment requirement of 9 months prior to cohort entry so that the first day of follow-up (on which acute pancreatitis could occur) will be characterized with the same level of detail (based on 9 months of preceding health insurance claims) as any other day during the study.
Consistent with the principle of minimal exclusions, we will only exclude from the cohorts people who have baseline claims associated with pancreatitis (in the 9-month period preceding cohort entry) as these people either had pre-existing pancreatitis or had a pre-existing suspicion of pancreatitis. We will not exclude persons with a type I diabetes diagnosis as we intend to observe the spectrum of clinical practice with respect to antidiabetic drug initiation.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Waltham, Massachusetts

Other trials in United States

About this study

Official title: A Retrospective Cohort Study of Acute Pancreatitis in Relation to Use of Byetta (Exenatide) and Other Antidiabetic Agents

The purpose of this research was to assess the absolute and relative incidence of acute pancreatitis in persons initiating exenatide compared with persons initiating a different antidiabetic agent, and secondarily, persons without diabetes. This protocol summarizes a retrospective cohort study using eligibility, pharmacy claims, and medical claims data from a large US health plan affiliated with i3 Drug Safety.

Read the detailed description

Limitations of the study: The results provided below should be interpreted in light of the following limitations:

Misclassification of acute pancreatitis may have distorted our estimates of absolute and relative IRs. In cases where the degree of misclassification is non-differential with respect to the exposure cohort, as is likely the case in administrative data, the RR would be biased toward the null value, although the magnitude of bias will depend on the amount of misclassification.
Lack of information on important potential confounders, like obesity and alcohol use, is another limitation of the present analysis. Although we adjusted for propensity scores of exenatide initiation, which included a large number of factors derived from the claims data, it is likely that the present estimates are somewhat inaccurate due to residual confounding.
Our definition of current use in the time-on-drug analysis, which extended 31 days past the nominal end of the last dispensing of the cohort-defining drug, may be too long in duration and thus misclassify exposure during the relevant etiologic period.
Additionally, these analyses assume that when pharmacies submit a claim for a medication that patients receive and consume the medication. While it is possible that misclassification of exposure by non-adherence to the medications dispensed occurred, prior work showed that pharmacy claims are valid for ascertaining medication exposure.

Conditions: Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies), Healthy Subjects (Treated With no Diabetes Therapies)
Being tested: exenatide, Other antidiabetic therapies, No diabetes therapy
Keywords: pancreatitis, exenatide, Byetta, Amylin, Lilly
Medical subject headings: Diabetes Mellitus, Type 2, Pancreatitis

What participants receive

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

exenatideDrug
Also called Byetta
subcutaneous injection, dosing according to normal clinical practice
Other antidiabetic therapiesDrug
Includes metformin, thiazolidinediones, insulins, sulfonylureas, non-sulfonylurea secretagogues, sitagliptin, and alpha-glucosidase inhibitors; In all cases, dosing according to normal clinical practice
No diabetes therapyOther
Subjects not diagnosed with diabetes

Study groups in NCT01077323
Study group	Role	What they receive
Exenatide Initiators		Not described Receives: Drug: exenatide
Other Antidiabetic Drug Initiators		Not described Receives: Drug: Other antidiabetic therapies
Non-Diabetes Cohort		Not described Receives: Other: No diabetes therapy

What is being measured

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

Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Current Use" Period) - Time on Drug Analysis
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is "current use" period, described as "time during current day's supply plus 31 days."
Measured: 43 months
Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (Among "Recent Use" Period) - Time on Drug Analysis
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is the "recent use" period, described as "time following current use plus an additional 31 days excluding subsequent current use."
Measured: 43 months
Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Past Use" Period) - Time on Drug Analysis
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is "past use" period, described as "time following recent use excluding subsequent current or recent use."
Measured: 43 months

Secondary outcomes (1)

Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis Among Initiators of Exenatide, Diabetics Initiating Other Antidiabetic Drugs, and the Non-diabetes Cohort - Intent to Treat Analysis
Crude intent-to-treat incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort.
Measured: 43 months

Timeline

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

Sep 2004Mar 2008

First posted1 Mar 2010 (estimated)
Study startSep 2004
Primary completionMar 2008
Study completionMar 2008

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 Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe 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: Retrospective
Enrolment: 363,766 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01077323
Sponsor's protocol ID: BCA406
Status last verified: Mar 2015
First submitted: 25 Feb 2010
Last updated: 15 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Retrospective Cohort Study of Acute Pancreatitis in Relation to Use of Byetta (Exenatide) and Other Antidiabetic Agents
ClinicalTrials.gov ID: NCT01077323
Acronym / sponsor ID: BCA406
Conditions: Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies), Healthy Subjects (Treated With no Diabetes Therapies)
Keywords: pancreatitis, exenatide, Byetta, Amylin, Lilly
Study type: Observational
Recruitment status: Completed
Enrolment: 363,766 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company, i3 Drug Safety
Study start: Sep 2004
Primary completion: Mar 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 1 Mar 2010 (estimated)
Results: Posted 6 Oct 2010

Clinical summary

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

Detailed description

Limitations of the study: The results provided below should be interpreted in light of the following limitations:

Misclassification of acute pancreatitis may have distorted our estimates of absolute and relative IRs. In cases where the degree of misclassification is non-differential with respect to the exposure cohort, as is likely the case in administrative data, the RR would be biased toward the null value, although the magnitude of bias will depend on the amount of misclassification.
Lack of information on important potential confounders, like obesity and alcohol use, is another limitation of the present analysis. Although we adjusted for propensity scores of exenatide initiation, which included a large number of factors derived from the claims data, it is likely that the present estimates are somewhat inaccurate due to residual confounding.
Our definition of current use in the time-on-drug analysis, which extended 31 days past the nominal end of the last dispensing of the cohort-defining drug, may be too long in duration and thus misclassify exposure during the relevant etiologic period.
Additionally, these analyses assume that when pharmacies submit a claim for a medication that patients receive and consume the medication. While it is possible that misclassification of exposure by non-adherence to the medications dispensed occurred, prior work showed that pharmacy claims are valid for ascertaining medication exposure.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 3

Arm	Type	Receives
Exenatide Initiators	–	Drug: exenatide
Other Antidiabetic Drug Initiators	–	Drug: Other antidiabetic therapies
Non-Diabetes Cohort	–	Other: No diabetes therapy

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: This retrospective study utilized medical claims data from a large US health plan affiliated with i3 Drug Safety. The individuals covered by this health plan are geographically diverse across the United States. The health plan provides fully insured coverage for physician, hospital and prescription drug services. The providers of these services submit their claims for payment directly to the health plan. i3 Drug Safety uses de-identified data derived from these claims daily for a wide range of safety, utilization, and economic analyses.

Key inclusion criteria (4 listed)

Exenatide Initiators: The date of the first dispensing of exenatide under which a potential cohort member might qualify will be 1 June 2005, and the latest date will be 31 December 2007. We will note the first initiation of exenatide, and also note subsequent initiation of other antidiabetic drugs. Eligible exenatide initiators will be included in the exenatide initiator cohort on the first eligible dispensing following at least 9 months of continuous health plan enrollment.
Other Antidiabetic Drug Initiators: The date of the first dispensing of an antidiabetic drug other than exenatide under which a potential cohort member might qualify will be 1 June 2005, and the latest date will be 31 December 2007. We will note the earliest date of other antidiabetic drug dispensings within their cohort membership, and also note subsequent initiation of other antidiabetic drugs. We will choose a subset of this comparator cohort randomly selected to be approximately 9 times larger than the exenatide initiators and will oversample patients receiving certain drugs to the extent necessary to ensure inclusion of at least as many persons initiating these drugs as initiating exenatide. Specifically, oversampling will be performed as needed on initiators of metformin, TZDs, SUs, sitagliptin and insulin glargine to allow for further sub-analysis.
Exenatide and Other Antidiabetic Drug Initiators: For all patients in these two study cohorts, the date of cohort entry (the date ranged between January 1, 2005 and December 31, 2007) marked the beginning of observation for study outcomes (follow-up). The end of observation for a given patient happened on the earliest of occurrence of likely acute pancreatitis, end of the study period (March 31, 2008), or disenrollment from the health plan.
Non-Diabetes Cohort: A third cohort will consist of randomly-selected Ingenix Research Data Mart members who have no claim associated with a diabetes diagnosis or antidiabetic drug dispensing in the baseline continuous enrollment period. This cohort will enter as of the later of 1 June 2005 or completion of 9 months continuous baseline enrollment and will provide follow-up through end of enrollment or 31 March 2008, or the receipt of an antidiabetic drug dispensing or diabetes diagnosis, at which point they may enter one of the other exposure cohorts.

Key exclusion criteria (2 listed)

The 3 cohorts (exenatide initiators, other antidiabetic initiators, and those without diabetes) will be subject to minimal exclusions in order to observe acute pancreatitis across a wide spectrum of patient characteristics. We will apply a baseline enrollment requirement of 9 months prior to cohort entry so that the first day of follow-up (on which acute pancreatitis could occur) will be characterized with the same level of detail (based on 9 months of preceding health insurance claims) as any other day during the study.
Consistent with the principle of minimal exclusions, we will only exclude from the cohorts people who have baseline claims associated with pancreatitis (in the 9-month period preceding cohort entry) as these people either had pre-existing pancreatitis or had a pre-existing suspicion of pancreatitis. We will not exclude persons with a type I diabetes diagnosis as we intend to observe the spectrum of clinical practice with respect to antidiabetic drug initiation.

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
exenatideAlso: Byettasubcutaneous injection, dosing according to normal clinical practice	Drug	Exenatide Initiators
Other antidiabetic therapiesIncludes metformin, thiazolidinediones, insulins, sulfonylureas, non-sulfonylurea secretagogues, sitagliptin, and alpha-glucosidase inhibitors; In all cases, dosing according to normal clinical practice	Drug	Other Antidiabetic Drug Initiators
No diabetes therapySubjects not diagnosed with diabetes	Other	Non-Diabetes Cohort

Primary outcome

Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Current Use" Period) - Time on Drug Analysis
Time frame: 43 months
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is "current use" period, described as "time during current day's supply plus 31 days."
Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (Among "Recent Use" Period) - Time on Drug Analysis
Time frame: 43 months
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is the "recent use" period, described as "time following current use plus an additional 31 days excluding subsequent current use."
Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Past Use" Period) - Time on Drug Analysis
Time frame: 43 months
Crude time-on-drug incidence rate per 100,000 person-years of likely acute pancreatitis in initiators of exenatide, initiators of other antidiabetic drugs and the non-diabetes cohort. Analysis period is "past use" period, described as "time following recent use excluding subsequent current or recent use."

1 secondary outcome

Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis Among Initiators of Exenatide, Diabetics Initiating Other Antidiabetic Drugs, and the Non-diabetes Cohort - Intent to Treat Analysis
Time frame: 43 months

Results and safety

Results posted to the registry on 6 Oct 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide Initiators	37,097	25,719
Other Antidiabetic Drug (OADs) Initiators	620,799	234,536
Non-Diabetes Cohort	12,015,600	103,511

Primary outcome: Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Current Use" Period) - Time on Drug Analysis

Time frame: 43 months. Number (95% Confidence Interval). Unit: Cases per 100,000 person-years

Measure	Exenatide Initiators n = 25719	Other Antidiabetic Drug (OADs) Initiators n = 234536	Non-Diabetes Cohort n = 103511
Value	219.7 (155.5 to 301.6)	226.7 (205.4 to 249.6)	56.2 (43.7 to 71.1)

Exenatide Initiators vs Other Antidiabetic Drug (OADs) Initiators: Adjusted Rate Ratio (ARR): 0.87 (95% CI 0.59 to 1.28)

Population analysed: Time on Drug Analysis

Primary outcome: Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (Among "Recent Use" Period) - Time on Drug Analysis

Time frame: 43 months. Number (95% Confidence Interval). Unit: Cases per 100,000 person-years

Measure	Exenatide Initiators n = 25719	Other Antidiabetic Drug (OADs) Initiators n = 234536	Non-Diabetes Cohort n = 103511
Value	321.4 (117.9 to 699.5)	325.5 (243.8 to 425.7)	56.2 (43.7 to 71.1)

Exenatide Initiators vs Other Antidiabetic Drug (OADs) Initiators: Adjusted Rate Ratio (ARR): 0.87 (95% CI 0.36 to 2.09)

Population analysed: Time on Drug Analysis

Primary outcome: Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Past Use" Period) - Time on Drug Analysis

Time frame: 43 months. Number (95% Confidence Interval). Unit: Cases per 100,000 person-years

Measure	Exenatide Initiators n = 25719	Other Antidiabetic Drug (OADs) Initiators n = 234536	Non-Diabetes Cohort n = 103511
Value	354.5 (245.5 to 495.4)	218.1 (183.0 to 258.0)	56.2 (43.7 to 71.1)

Exenatide Initiators vs Other Antidiabetic Drug (OADs) Initiators: Adjusted Rate Ratio (ARR): 1.39 (95% CI 0.86 to 2.25)

Population analysed: Time on Drug Analysis

1 secondary outcome is reported in the full results.

Adverse events

Time frame: SERIOUS ADVERSE EVENTS AND ADVERSE EVENTS NOT APPLICABLE (please see additional description below).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide Initiators	0 of 0	0 of 0	Not reported
Other Antidiabetic Drug (OADs) Initiators	0 of 0	0 of 0	Not reported
Non-Diabetes Cohort	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 15 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

Vice President Research and Development, MD study director

Amylin Pharmaceuticals, LLC.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 2 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 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 6 Oct 2010). 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?

Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Current Use" Period) - Time on Drug Analysis (time frame: 43 months). The study lists 3 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 NCT01077323.

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 15 Apr 2015.