Safety Study of Atomoxetine and Cerebrovascular Outcomes

Atomoxetine and Cerebrovascular Outcomes in Adults

Using a proprietary insurance health claims database, Eli Lilly and Company has contracted with an external party to conduct a retrospective cohort study of health claims for the time period from 1 January 2003 through 31 December 2006 (with follow-up of patients through 30 June 2007). This study will evaluate the potential association between atomoxetine and cerebrovascular events. In this study, the incidence of selected cerebrovascular outcomes as represented in health claims data among adult patients who initiate therapy with atomoxetine will be estimated. In particular the study will focus on cerebrovascular accident (CVA) and transient ischemic attack (TIA) as the outcomes of interest. The incidence for each outcome among atomoxetine initiators will then be compared to the incidence in a cohort of similar patients who initiate stimulant treatment and an age and gender-matched general population cohort. The atomoxetine and stimulant-initiating cohorts will be matched on a broad variety of variables, including age, gender, diagnoses, medication use, and healthcare utilization through the use of propensity score matching in order to minimize the influence of confounding by indication. The analysis will include the cohorts (atomoxetine and stimulant initiators) from a previous completed study with increased follow-up time (1 January 2003 through 30 June 2007) and accrue new atomoxetine and stimulant ADHD medication initiators over a 2 year period, so that the study will represent initiators between January 1, 2003 and December 31, 2006 with follow-up through June 30, 2007.

Study Overview

• Status: Completed
• Conditions: Transient Ischemic Attack; ADHD; Cerebrovascular Accident
• Intervention / Treatment: Drug: atomoxetine; Drug: Stimulants; Other: No intervention (general population)

• Study Type: Observational
• Enrollment (Anticipated): 72000

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The source population is derived from the proprietary Ingenix RDM, with a cross-sectional population of approximately 12 million current health plan members across the US at the beginning of 2007 who have both medical and prescription benefit coverage.

Description

Inclusion Criteria:

• patients 18 years or older
• received dispensing of one of the study medications during the time period of the study (January 1, 2003 - December 31, 2006)
• 6 months of continuous enrollment prior to first dispensing

Exclusion Criteria:

• presence of pre-existing arrhythmia and heart failure during the baseline period

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A; All patients 18 years or older who received a first dispensing of atomoxetine during the time period of the study (January 1, 2003 through December 31, 2006) and had at least 6 months of continuous enrollment prior to first dispensing are included in the study cohort. Patients are excluded for presence of pre-existing arrhythmia and heart failure during the baseline period. The study entry date for this cohort is the date of first atomoxetine dispensing.	Drug: atomoxetine; Other Names: LY139603; Strattera
B; All patients 18 years or older who received a first dispensing of a stimulant medication (methylphenidate or mixed salts of amphetamine) during the time period of the study with no dispensing of the same drug in the prior 6 months and had at least 6 months of continuous enrollment prior to the first dispensing are identified. Patients are excluded for presence of pre-existing arrhythmia and heart failure during the baseline period. Patients who are matched to atomoxetine initiators using this propensity score method are retained and followed as one comparator cohort. The study entry date is the date of the first dispensing of a comparator ADHD medication.	Drug: Stimulants; Methylphenidate, amphetamines (including Adderall and mixed salts)
C; Patients with at least 6 months of continuous enrollment in the database, and without a history of arrhythmia or heart failure during the baseline period are sampled and frequency matched on age and gender to the atomoxetine cohort in a 2:1 ratio. Study entry dates are assigned so as to be similar to the distribution of study entry dates in the atomoxetine cohort. Patients identified and matched as initiators of atomoxetine or stimulant ADHD medications are not eligible for inclusion in this cohort	Other: No intervention (general population)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cerebrovascular Accident (CVA)	January 2003 - June 2007
Transient Ischemic Attack (TIA)	January 2003 - June 2007

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: i3 Drug Safety
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9AM- 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: March 4, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): September 15, 2009
• Last Update Submitted That Met QC Criteria: September 14, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: stroke; ADHD; attention deficit hyperactivity disorder; cerebrovascular accident; transient ischemic attack; TIA; CVA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Attack, Transient; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 12414; B4Z-MC-B014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No