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Carcinogenicity Study of Bupropion

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01077596
First received: February 25, 2010
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

There is a lack of toxicology data on one bupropion metabolite, and limited literature examining bupropion use and cancer risk. This study evaluates the association between bupropion exposure and the development of cancer of the prostate, breast, lung, colon/rectum, urinary bladder, and uterus by comparing the risk of cancer in bupropion users with other antidepressant users. Because there is no evidence that bupropion is associated with any particular cancer, we have chosen the six most common cancers diagnosed in the United States to optimize statistical power/precision for cancer-site specific comparisons. Two US population-based data resources with automated claims, pharmacy, and tumor registry data are included in this study. Using a nested case-control design, this study will compare the incidence of cancer in patients exposed to bupropion with the incidence in patients exposed to other antidepressants.


Condition Intervention
Depressive Disorder
Cancer
Drug: Regular bupropion use
Drug: Regular SSRI (Selective serotonin reuptake inhibitors) use
Drug: Regular TCA (Tricyclic antidepressants) use
Drug: Regular use of any other antidepressant

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Post-marketing Carcinogenicity Study of Bupropion

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Diagnosed With Any of the Cancers Under Investigation Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    The following are the cancers under investigation: colorectal, lung, bladder, uterus, breast, and prostate. Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.


Secondary Outcome Measures:
  • Number of Participants Diagnosed With Colorectal Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, colorectal cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Colorectal cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.

  • Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, lung cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Lung cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.

  • Number of Participants Diagnosed With Bladder Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, bladder cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Bladder cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.

  • Number of Participants Diagnosed With Uterine Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, uterine cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Uterine cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.

  • Number of Participants Diagnosed With Breast Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, breast cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Breast cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.

  • Number of Participants Diagnosed With Prostate Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ] [ Designated as safety issue: Yes ]
    In this outcome, prostate cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Prostate cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.


Enrollment: 50430
Study Start Date: June 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
New users of antidepressants Jan. 1, 1996 to Dec. 31, 2006
All new users of antidepressants January 1, 1996 through December 31, 2006. Individuals 18 years of age or older with medical and pharmacy benefits and at least 6 months of health plan enrollment before the first antidepressant prescription.
Drug: Regular bupropion use
Regular use of bupropion is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.
Drug: Regular SSRI (Selective serotonin reuptake inhibitors) use
Regular use of SSRI is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.
Drug: Regular TCA (Tricyclic antidepressants) use
Regular use of TCA is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.
Drug: Regular use of any other antidepressant
Regular use of any other antidepressants is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date. An "other antidepressant" would be any antidepressant other than bupropion, a SSRI or a TCA.

Detailed Description:

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

New users of antidepressants January 1, 1996 through December 31, 2006, regardless of indication for use (depression, smoking cessation, other) in Henry Ford Health System and Kaiser Permanente Health Plan of Northern California. The study population is limited to individuals 18 years of age or older with medical and pharmacy benefits and at least 6 months of health plan enrollment before the first antidepressant prescription. Patients with a history of any cancer (cancer diagnosis recorded in the tumor registries anytime before the first antidepressant prescription recorded during the study period) are excluded. Cases and controls will be selected from this cohort of antidepressant-exposed study subjects.

Criteria

Inclusion Criteria:

-

Exclusion Criteria:

  • Cancers diagnosed within 12 months of initiation (i.e., new use) of antidepressant pharmacotherapy will be excluded to account for a minimum period for the development of cancer (cancer latency) and to be consistent with other studies of antidepressants and cancer.
  • Patients with a history of any cancer (cancer diagnosis recorded in the tumor registries anytime before the first antidepressant prescription recorded during the study period)
  • Any antidepressant use within 6 months of January 1, 1996
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077596

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01077596     History of Changes
Other Study ID Numbers: 111982, EPI40463, WEUKSTV1113
Study First Received: February 25, 2010
Results First Received: January 21, 2011
Last Updated: June 2, 2011
Health Authority: United Kingdom: No Health Authority

Keywords provided by GlaxoSmithKline:
Carcinogenicity
Case control
Bupropion

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Antidepressive Agents, Tricyclic
Bupropion
Serotonin Uptake Inhibitors
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014