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

History of Changes

Results First Received: January 21, 2011

Study Type:	Observational
Study Design:	Observational Model: Case Control; Time Perspective: Retrospective
Conditions:	Depressive Disorder Cancer
Interventions:	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

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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 anonymized and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
New Antidepressant Exposure in Colorectal Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Colorectal Cancer: Cases
New Antidepressant Exposure in Colorectal Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Colorectal Cancer: Controls
New Antidepressant Exposure in Lung Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Lung Cancer: Cases
New Antidepressant Exposure in Lung Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Lung Cancer: Controls
New Antidepressant Exposure in Bladder Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Bladder Cancer: Cases
New Antidepressant Exposure in Bladder Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Bladder Cancer: Controls
Antidepressant Exposure in Uterine Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Uterine Cancer: Cases
New Antidepressant Exposure in Uterine Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Uterine Cancer: Controls
New Antidepressant Exposure in Breast Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Breast Cancer: Cases
New Antidepressant Exposure in Breast Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Breast Cancer: Controls
New Antidepressant Exposure in Prostate Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Prostate Cancer: Cases
New Antidepressant Exposure in Prostate Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Prostate Cancer: Controls

Participant Flow: Overall Study

	New Antidepressant Exposure in Colorectal Cancer: Cases	New Antidepressant Exposure in Colorectal Cancer: Controls	New Antidepressant Exposure in Lung Cancer: Cases	New Antidepressant Exposure in Lung Cancer: Controls	New Antidepressant Exposure in Bladder Cancer: Cases	New Antidepressant Exposure in Bladder Cancer: Controls	Antidepressant Exposure in Uterine Cancer: Cases	New Antidepressant Exposure in Uterine Cancer: Controls	New Antidepressant Exposure in Breast Cancer: Cases	New Antidepressant Exposure in Breast Cancer: Controls	New Antidepressant Exposure in Prostate Cancer: Cases	New Antidepressant Exposure in Prostate Cancer: Controls
STARTED	350	1050	457	1370	294	882	308	837	2842	28420	2215	22150
COMPLETED	350	1050	457	1370	294	882	308	837	2842	28420	2215	22150
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
New Antidepressant Exposure in Colorectal Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Colorectal Cancer: Cases
New Antidepressant Exposure in Colorectal Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Colorectal Cancer: Controls
New Antidepressant Exposure in Lung Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Lung Cancer: Cases
New Antidepressant Exposure in Lung Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Lung Cancer: Controls
New Antidepressant Exposure in Bladder Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Bladder Cancer: Cases
New Antidepressant Exposure in Bladder Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Bladder Cancer: Controls
New Antidepressant Exposure in Uterine Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Uterine Cancer: Cases
New Antidepressant Exposure in Uterine Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Uterine Cancer: Controls
New Antidepressant Exposure in Breast Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Breast Cancer: Cases
New Antidepressant Exposure in Breast Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Breast Cancer: Controls
New Antidepressant Exposure in Prostate Cancer: Cases	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Prostate Cancer: Cases
New Antidepressant Exposure in Prostate Cancer: Controls	New Antidepressant Exposure (defined as no antidepressant exposure within previous 6 months) in Prostate Cancer: Controls
Total	Total of all reporting groups

Baseline Measures

	New Antidepressant Exposure in Colorectal Cancer: Cases	New Antidepressant Exposure in Colorectal Cancer: Controls	New Antidepressant Exposure in Lung Cancer: Cases	New Antidepressant Exposure in Lung Cancer: Controls	New Antidepressant Exposure in Bladder Cancer: Cases	New Antidepressant Exposure in Bladder Cancer: Controls	New Antidepressant Exposure in Uterine Cancer: Cases	New Antidepressant Exposure in Uterine Cancer: Controls	New Antidepressant Exposure in Breast Cancer: Cases	New Antidepressant Exposure in Breast Cancer: Controls	New Antidepressant Exposure in Prostate Cancer: Cases	New Antidepressant Exposure in Prostate Cancer: Controls	Total
Number of Participants [units: participants]	350	1050	457	1370	294	882	308	837	2842	28420	2215	22150	61175
Age, Customized [units: Participants]
45-54 years	34	102	47	140	17	51	59	172	678	6780	193	1930	10203
55-64 years	73	219	102	306	63	189	90	245	849	8490	669	6690	17985
65-74 years	119	357	159	477	104	312	84	224	707	7070	877	8770	19260
>=75 years	124	372	149	447	110	330	75	196	608	6080	476	4760	13727
Gender [units: Participants]
Female	126	378	175	525	91	273	308	837	2842	28420	0	0	33975
Male	224	672	282	845	203	609	0	0	0	0	2215	22150	27200
Number of participants diagnosed with the indicated conditions and using the indicated therapies ^[1] [units: participants]
Exposed to multiple antidepressants	47	160	62	191	44	147	53	162	564	5756	340	3782	11308
Ever smokers	252	643	428	772	247	573	142	389	0	0	0	0	3446
Unknown smoking status	4	70	5	183	1	29	4	27	0	0	0	0	323
Ever diagnosed (dx) with depression	110	329	108	408	83	273	119	319	1091	10541	677	6700	20758
Ever dx with inflammatory bowel disease (IBD)	1	9	0	0	0	0	0	0	0	0	0	0	10
Users of oral contraceptives (OC)	6	7	0	0	0	0	8	45	236	1987	0	0	2289
Users of hormone replacement therapy (HRT)	57	225	0	0	0	0	153	441	1796	17184	0	0	19856
Users of NSAIDs	269	859	370	1123	0	0	0	0	2340	23730	1800	17887	48378

[1]	A value of “0” indicates that no data are available for that particular treatment arm. Smoking status data were not collected for breast cancer and prostate cancer cases and controls, as it is not a necessary variable for analysis. NSAIDS, non-steroidal anti-inflammatory drugs.

Outcome Measures

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1. Primary:

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 ]

Show Outcome Measure 1

2. Secondary:

Number of Participants Diagnosed With Colorectal Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

Show Outcome Measure 2

3. Secondary:

Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

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Measure Type	Secondary
Measure Title	Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant
Measure Description	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.
Time Frame	January 1, 1996 – December 31, 2006
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants diagnosed with lung cancer who were new antidepressant users.

Reporting Groups

	Description
Bupropion, Regular Use	Regular Bupropion use was defined as 4 times per week for 3 months at least 12 months before index date
All Non-bupropion Antidepressants, Regular Use	Regular antidepressant use of non-bupropion was defined as use of non-bupropion antidepressant for 4 times per week for 3 months at least 12 months before index date
Tricyclic Antidepressants (TCA), Regular Use	Regular TCA use was defined as use of tricyclic antidepressant for 4 times per week for 3 months at least 12 months before index date
Selective Serotonin Reuptake Inhibitors (SSRI), Regular Use	Regular SSRI use was defined as use of SSRI antidepressant for 4 times per week for 3 months at least 12 months before index date
Other Antidepressants, Regular Use	Regular ‘other’ antidepressant use was defined as use other antidepressant aside from Bupropion, TCA and SSRI for 4 times per week for 3 months at least 12 months before index date

Measured Values

	Bupropion, Regular Use	All Non-bupropion Antidepressants, Regular Use	Tricyclic Antidepressants (TCA), Regular Use	Selective Serotonin Reuptake Inhibitors (SSRI), Regular Use	Other Antidepressants, Regular Use
Number of Participants Analyzed [units: participants]	240	1172	498	670	233
Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant [units: participants]
Cases	115	250	109	138	47
Controls	125	922	389	532	186

Statistical Analysis 1 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. All Non-bupropion Antidepressants, Regular Use
Crude Odds Ratio ^[2]	4.5
95% Confidence Interval	( 3.2 to 6.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. All Non-bupropion Antidepressants, Regular Use
Adjusted Odds Ratio ^[2]	3.0
95% Confidence Interval	( 2.0 to 4.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Adjusted for age, sex, cal year, study site, tumor characteristics, multiple antidepressants exposure, smoking, hysterectomy status, previous depression dx, previous IBD diagnosis, OC use, HRT/ERT use, and NSAID use.

Statistical Analysis 3 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Tricyclic Antidepressants (TCA), Regular Use
Crude Odds Ratio ^[2]	4.0
95% Confidence Interval	( 2.8 to 5.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Tricyclic Antidepressants (TCA), Regular Use
Adjusted Odds Ratio ^[2]	2.9
95% Confidence Interval	( 1.9 to 4.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Adjusted for age, sex, cal year, study site, tumor characteristics, multiple antidepressants exposure, smoking, hysterectomy status, previous depression dx, previous IBD diagnosis, OC use, HRT/ERT use, and NSAID use.

Statistical Analysis 5 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Selective Serotonin Reuptake Inhibitors (SSRI), Regular Use
Crude Odds Ratio ^[2]	4.4
95% Confidence Interval	( 3.1 to 6.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Selective Serotonin Reuptake Inhibitors (SSRI), Regular Use
Adjusted Odds Ratio ^[2]	3.0
95% Confidence Interval	( 1.9 to 4.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Adjusted for age, sex, cal year, study site, tumor characteristics, multiple antidepressants exposure, smoking, hysterectomy status, previous depression dx, previous IBD diagnosis, OC use, HRT/ERT use, and NSAID use.

Statistical Analysis 7 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Other Antidepressants, Regular Use
Crude Odds Ratio ^[2]	4.5
95% Confidence Interval	( 2.8 to 7.2 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant

Groups ^[1]	Bupropion, Regular Use vs. Other Antidepressants, Regular Use
Adjusted Odds Ratio ^[2]	3.5
95% Confidence Interval	( 2.1 to 5.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Adjusted for age, sex, cal year, study site, tumor characteristics, multiple antidepressants exposure, smoking, hysterectomy status, previous depression dx, previous IBD diagnosis, OC use, HRT/ERT use, and NSAID use.

4. Secondary:

Number of Participants Diagnosed With Bladder Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

Show Outcome Measure 4

5. Secondary:

Number of Participants Diagnosed With Uterine Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

Show Outcome Measure 5

6. Secondary:

Number of Participants Diagnosed With Breast Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

Show Outcome Measure 6

7. Secondary:

Number of Participants Diagnosed With Prostate Cancer Who Were Regularly Exposed to the Indicated Antidepressant [ Time Frame: January 1, 1996 – December 31, 2006 ]

Show Outcome Measure 7

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

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

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