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

NCT00749944 | Completed Phase 4 Results

• 1 other identifier: A3051115
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

Brief Summary

Study objective is to compare neuropsychiatric adverse events in subjects treated with varenicline or placebo in a controlled setting where both groups are experiencing nicotine withdrawal.

Conditions

Smoking Cessation

Keywords

nicotine withdrawal, smoking cessation, varenicline

Outcome Measures

Primary Outcomes (14)

• Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD)

  POMS TMD were responses to 65 items in 6 subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion), on 'How you feel right now?' (scale:0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for Relaxed and Efficient in the Tension-Anxiety and Confusion subscales. TMD was the sum of the scores of all 6 subscales but weighting Vigor negatively. Summary results (TMD scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale

  POMS Tension-Anxiety subscale data were responses to 9 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Relaxed. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale

  POMS Depression-Dejection subscale data responses to 15 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale

  POMS Anger-Hostility subscale data were responses to 12 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale

  POMS Vigor subscale data were responses to 8 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale

  POMS Fatigue subscale data were responses to 7 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale

  POMS Confusion subscale data were responses to 7 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Efficient. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

  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).

• Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score

  The MADRS measures the overall severity of depressive symptoms and is a 10-item checklist. Each item was rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

  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).

• Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score

  HAM-A measures treatment-related changes in generalized anxiety symptoms and is a 14-item questionnaire. Each item was scored from 0 (not present) to 4 (very severe) and a lower score indicated less affected. Total scores ranged from 0 (not affected) to 56 (very severely affected).

  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).

• Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score

  The OAS-m contains 3 scales: Aggression (Questions \[Q\]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Aggression total score was calculated by summing the weighted scores in Q1 to 4. Scores for each question ranged from 0 (no events) to 5 (very severe events). Total scores ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week.

  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).

• Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score

  The OAS-m contains 3 scales: Aggression (Questions \[Q\]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Irritability total score was calculated by summing the items in Q5 to 6. Scores for each question ranged from 0 (not at all) to 5 (extreme). Total scores ranged from 0 (no irritability) to 10 (extreme irritability).

  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).

• Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Suicidality Total Score

  The OAS-m contains 3 scales: Aggression (Questions \[Q\]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Suicidality total score was calculated by summing the items Q7 to 7b. Scores for Q7 ranged from 0 (none) to 6 (very extreme) and scores for Q7a to 7b ranged from 0 (none) to 5 (extreme). Total scores ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency).

  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).

• Change From Baseline in the Social Dysfunction and Aggression Scale (SDAS): Total Score

  The SDAS contains 11 items with 5 possible responses: 0=not present, 1=doubtful or very mild, 2=mild to moderate, 3=severe, and 4=extremely severe. The SDAS was collected 3 times a day during the inpatient abstinence period (BC). Total scores ranged from 0 (not present) to 44 (extremely severe).

  Baseline B (Week 2) to Week 4 (Period BC)

• Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score

  The BIS-11 is a 30-item self-report questionnaire designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Possible responses to each item were: 1=rarely/never, 2=occasionally, 3=often, and 4=almost always/always. Scores of Items 1, 7, 8, 9, 10, 12, 13, 15, 20, 29 and 30 were reversed when calculating the total score. Total score ranged from 30 (less impulsive) to 120 (more impulsive).

  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).

Secondary Outcomes (17)

• Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score

  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).

• Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale

  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).

• Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale

  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).

• Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale

  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).

• Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale

  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).

Study Arms (2)

varenicline

EXPERIMENTAL

Drug: varenicline

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

varenicline DRUG

1 mg tablets twice daily by mouth (after one week of uptitration: 0.5mg once daily for three days, 0.5mg twice daily for four days)

Also known as: Chantix, Champix

varenicline

placebo DRUG

1 mg tablets twice daily by mouth (after one week of uptitration: 0.5mg once daily for three days, 0.5mg twice daily for four days)

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• smokers who smoke \>10 cigarettes/day and who have at least a moderate level of addiction as measured by the Fagerstrom Test for Nicotine Dependence (score \>5)

You may not qualify if:

• Any neuropsychiatric disease including depression, history of suicidal thoughts or behavior, bipolar disorder.
• Any unstable medical condition

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Pfizer Investigational Site

Austin, Texas, 78759, United States

Location

Pfizer Investigational Site

San Antonio, Texas, 78217, United States

Location

Related Publications (1)

• 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. doi: 10.1016/j.biopsych.2010.12.005. Epub 2011 Feb 3.

  PMID: 21295286 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Smoking Cessation

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 9, 2008
• First Posted: September 10, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: August 1, 2009
• Last Updated: August 31, 2010
• Results First Posted: August 9, 2010

Record last verified: 2010-08

Locations

US (2)