Carcinogenicity Study of Bupropion

• ClinicalTrials.gov Identifier: NCT01077596
• Recruitment Status: Completed
• First Posted: March 1, 2010
• Results First Posted: February 10, 2011
• Last Update Posted: May 30, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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 or disease	Intervention/treatment
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

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 50430 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Post-marketing Carcinogenicity Study of Bupropion
• Study Start Date: June 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Groups and Cohorts

Group/Cohort

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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 :

1. Number of Participants Diagnosed With Colorectal Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.
2. Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.
3. Number of Participants Diagnosed With Bladder Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.
4. Number of Participants Diagnosed With Uterine Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.
5. Number of Participants Diagnosed With Breast Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.
6. Number of Participants Diagnosed With Prostate Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 - December 31, 2006 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01077596
• Other Study ID Numbers: 111982; EPI40463; WEUKSTV1113
• First Posted: March 1, 2010
• Results First Posted: February 10, 2011
• Last Update Posted: May 30, 2017
• Last Verified: May 2017

Keywords provided by GlaxoSmithKline:

Carcinogenicity; Case control; Bupropion

Additional relevant MeSH terms:

Depressive Disorder; Mood Disorders; Mental Disorders; Bupropion; Antidepressive Agents; Antidepressive Agents, Tricyclic; Serotonin; Serotonin Uptake Inhibitors; Antidepressive Agents, Second-Generation; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Serotonin Receptor Agonists; Serotonin Agents