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

This study has been completed.
Sponsor:
Collaborators:
Eli Lilly and Company
i3 Drug Safety
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01077323
First received: February 25, 2010
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Type 2 Diabetes (Treated With Exenatide or Other Oral Antidiabetic Therapies)
Healthy Subjects (Treated With no Diabetes Therapies)
Drug: exenatide
Drug: Other antidiabetic therapies
Other: No diabetes therapy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Retrospective Cohort Study of Acute Pancreatitis in Relation to Use of Byetta (Exenatide) and Other Antidiabetic Agents

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Incidence Rates Per 100,000 Person-Years of Likely Acute Pancreatitis (During "Current Use" Period) - Time on Drug Analysis [ Time Frame: 43 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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."


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 363766
Study Start Date: September 2004
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Exenatide Initiators Drug: exenatide
subcutaneous injection, dosing according to normal clinical practice
Other Name: Byetta
Other Antidiabetic Drug Initiators Drug: Other antidiabetic therapies
Includes metformin, thiazolidinediones, insulins, sulfonylureas, non-sulfonylurea secretagogues, sitagliptin, and alpha-glucosidase inhibitors; In all cases, dosing according to normal clinical practice
Non-Diabetes Cohort Other: No diabetes therapy
Subjects not diagnosed with diabetes

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.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01077323

Locations
United States, Massachusetts
Research Site
Waltham, Massachusetts, United States
Sponsors and Collaborators
Bristol-Myers Squibb
Eli Lilly and Company
i3 Drug Safety
Investigators
Study Director: Vice President Research and Development, MD Amylin Pharmaceuticals, LLC.
  More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01077323     History of Changes
Other Study ID Numbers: BCA406
Study First Received: February 25, 2010
Results First Received: August 12, 2010
Last Updated: October 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Bristol-Myers Squibb:
pancreatitis
exenatide
Byetta
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Pancreatitis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pancreatic Diseases
Digestive System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014