Assessing Neuropsychiatric Symptoms Including Depression, Anxiety, Irritability, and Suicidal Thoughts or Behavior in Subjects Quitting Smoking on Varenicline Tartrate or Placebo

This study has been completed.

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00749944

First received: September 9, 2008

Last updated: August 24, 2010

Last verified: August 2010

History of Changes

Results First Received: July 7, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Condition:	Smoking Cessation
Interventions:	Drug: varenicline Drug: placebo

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
857 participants were screened; 110 participants met the criteria for inclusion into the study and were assigned to study treatment

Reporting Groups

	Description
Varenicline	Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (starting on Day 8, the first day of Week 2)
Placebo	Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)

Participant Flow: Overall Study

	Varenicline	Placebo
STARTED	55	55
COMPLETED	50	54
NOT COMPLETED	5	1
Lost to Follow-up	2	1
Not specified	1	0
Withdrawal by Subject	2	0

Baseline Characteristics

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Reporting Groups

	Description
Varenicline	Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (starting on Day 8, the first day of Week 2)
Placebo	Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Total	Total of all reporting groups

Baseline Measures

	Varenicline	Placebo	Total
Number of Participants [units: participants]	55	55	110
Age, Customized [units: Participants]
Between 18 and 44 years	47	47	94
Between 45 and 64 years	7	8	15
>= 65 years	1	0	1
Gender [units: Participants]
Female	22	15	37
Male	33	40	73

Outcome Measures

Show All Outcome Measures

1. Primary:

Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 1

2. Primary:

Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 2

3. Primary:

Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 3

4. Primary:

Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 4

5. Primary:

Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 5

6. Primary:

Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 6

7. Primary:

Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 7

8. Primary:

Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 8

9. Primary:

Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 9

10. Primary:

Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 10

11. Primary:

Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 11

12. Primary:

Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Suicidality Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 12

13. Primary:

Change From Baseline in the Social Dysfunction and Aggression Scale (SDAS): Total Score [ Time Frame: Baseline B (Week 2) to Week 4 (Period BC) ]

Show Outcome Measure 13

14. Primary:

Change From Baseline in the Barratt Impulsiveness Scale – Version 11 (BIS-11): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 14

15. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 16

17. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 17

18. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 20

21. Secondary:

Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 21

22. Secondary:

Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 22

23. Secondary:

Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 23

24. Secondary:

Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 24

25. Secondary:

Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 25

26. Secondary:

Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Suicidality Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 26

27. Secondary:

Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale – Version 11 (BIS-11): Total Score [ Time Frame: Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE). ]

Show Outcome Measure 27

28. Secondary:

Number of Participants Exceeding Thresholds for the Social Dysfunction and Aggression Scale (SDAS): Total Score [ Time Frame: Baseline B (Week 2) to Week 4 (Period BC) ]

Show Outcome Measure 28

29. Secondary:

Number of Participants With Carbon Monoxide Confirmed Daily Smoking Cessation [ Time Frame: Week 9 to Week 12 ]

Show Outcome Measure 29

30. Secondary:

Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) [ Time Frame: Week 5 to Week 13 ]

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Measure Type	Secondary
Measure Title	Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation)
Measure Description	Participants who reported no smoking and no use of other nicotine-containing products since the last study visit (during treatment) in the previous 7 days and who did not have carbon monoxide of more than 10 parts per million for that observation (if measured).
Time Frame	Week 5 to Week 13
Safety Issue	No

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.
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.

Reporting Groups

	Description
Varenicline	Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (starting on Day 8, the first day of Week 2)
Placebo	Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)

Measured Values

	Varenicline	Placebo
Number of Participants Analyzed [units: participants]	55	55
Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) [units: participants]
Week 5 (n=55, 55)	19	16
Week 6 (n=55, 55)	23	12
Week 7 (n=55, 55)	20	17
Week 8 (n=55, 55)	21	15
Week 9 (n=55, 55)	25	14
Week 10 (n=55, 55)	17	17
Week 11 (n=55, 55)	20	18
Week 12 (n=55, 55)	19	15
Week 13 (n=55, 55)	23	15

No statistical analysis provided for Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation)

31. Secondary:

Change From Baseline in the Number of Cigarettes Smoked Per Day [ Time Frame: Baseline (Week 0) to Week 2 ]

Show Outcome Measure 31

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: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

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: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

No publications provided by Pfizer

Publications automatically indexed to this study:

Garza D, Murphy M, Tseng LJ, Riordan HJ, Chatterjee A. A double-blind randomized placebo-controlled pilot study of neuropsychiatric adverse events in abstinent smokers treated with varenicline or placebo. Biol Psychiatry. 2011 Jun 1;69(11):1075-82. Epub 2011 Feb 3.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00749944 History of Changes
Other Study ID Numbers:	A3051115
Study First Received:	September 9, 2008
Results First Received:	July 7, 2010
Last Updated:	August 24, 2010
Health Authority:	United States: Food and Drug Administration

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