Smoking Cessation
Conditions
Keywords
nicotine withdrawal, smoking cessation, varenicline
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.
Interventions
DRUGvarenicline
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)
DRUGplacebo
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)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* Any neuropsychiatric disease including depression, history of suicidal thoughts or behavior, bipolar disorder. * Any unstable medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Vigor 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Fatigue 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). | 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). |
| Change From Baseline in the Profile of Mood States (POMS): Confusion 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). | 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). |
| Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): 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). | 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). |
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A): 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). | 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). |
| Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression 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). | 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. |
| Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability 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). | 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). |
| Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Suicidality 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). | 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). |
| Change From Baseline in the Social Dysfunction and Aggression Scale (SDAS): Total Score | Baseline B (Week 2) to Week 4 (Period BC) | 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). |
| Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): 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). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Carbon Monoxide Confirmed Daily Smoking Cessation | Week 9 to Week 12 | Participants who reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory, which was used to collect the information of cigarette or other nicotine use during the study) and who did not have carbon monoxide of more than 10 parts per million at any time from Week 9 to Week 12 |
| 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). | The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Total scores were the average score for all 9 items and ranged from 0 (no withdrawal symptoms) to 4 (extreme withdrawal symptoms). |
| Change From Baseline in the Number of Cigarettes Smoked Per Day | Baseline (Week 0) to Week 2 | — |
| Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 5 to Week 13 | 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). |
| 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). | The MNWS negative affect domain subscale contains 4 items (depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average from all 4 items and ranged from 0 (no negative affect) to 4 (extreme negative affect). |
| 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). | The MNWS insomnia domain subscale contains 2 items (difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average of the 2 items and ranged from 0 (no insomnia) to 4 (extreme insomnia). |
| 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). | The MNWS urge to smoke subscale contains 1 item (urge to smoke) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no urge to smoke) to 4 (extreme urge to smoke). |
| 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). | The MNWS restlessness subscale contains 1 item (restlessness) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no restlessness) to 4 (extreme restlessness). |
| Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite 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). | The MNWS increased appetite subscale contains 1 item (increased appetite) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no increased appetite) to 4 (extreme increased appetite). |
| Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): 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). | POMS total mood disturbance (TMD) summary results were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance). Participants exceeding the threshold had an increase from baseline of 1 standard deviation of the TMD baseline T-score plus 1 or more. |
| Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): 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). | The MADRS measures the overall severity of depressive symptoms. Total score ranged from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Participants exceeding the threshold had a MADRS total score of more than 14 out of 60. MADRS total scores exceeding 14 may represent clinically notable effective symptomatology. |
| Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): 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). | HAM-A measures treatment-related changes in generalized anxiety symptoms. Total scores ranged from 0 (not affected) to 56 (very severely affected). Participants exceeding the threshold had a HAM-A total score of more than or equal to 14 out of 56. HAM-A total scores of more than or equal to 14 may reflect clinically noteworthy levels of anxiety. |
| Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression 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). | The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Aggression total score ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week. Participants exceeding the threshold had an OAS-m Aggression total score of more than or equal to 3 out of any number with no upper limit depending on the frequency of agressive behaviour in a week. OAS-m Aggression total scores of more than or equal to 3 reflect clinically important aggression. |
| Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability 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). | The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Irritability total score ranged from 0 (no irritability) to 10 (extreme irritability). Participants exceeding the threshold had an OAS-m Irritability total score of more than or equal to 2 out of 10. OAS-m Irritability total scores of more than or equal to 2 reflect clinically important irritability. |
| Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Suicidality 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). | The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Suicidality total score ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency). No threshold criterion was determined for OAS-m Suicidality total score. |
| Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): 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). | The BIS-11 is designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Total score ranged from 30 (less impulsive) to 120 (more impulsive). Participants exceeding the threshold had a BIS-11 total score more than or equal to 70 out of 120. BIS-11 total scores of more than or equal to 70 could reflect clinically important and potentially pathological impulsivity. |
| Number of Participants Exceeding Thresholds for the Social Dysfunction and Aggression Scale (SDAS): Total Score | Baseline B (Week 2) to Week 4 (Period BC) | SDAS total scores ranged from 0 (not present) to 44 (extremely severe). Participants exceeding the threshold had a SDAS total score of more than 6 out of 44. |
Countries
United States
Participant flow
Pre-assignment details
857 participants were screened; 110 participants met the criteria for inclusion into the study and were assigned to study treatment
Participants by arm
| Arm | Count |
|---|---|
| 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) | 55 |
| 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) | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Varenicline |
|---|---|---|---|
| Age, Customized >= 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Between 18 and 44 years | 94 Participants | 47 Participants | 47 Participants |
| Age, Customized Between 45 and 64 years | 15 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Female | 37 Participants | 15 Participants | 22 Participants |
| Sex: Female, Male Male | 73 Participants | 40 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 55 | 52 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AD (n=54, 54) | 1.34 scores on a scale | Standard Error 0.74 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BC (n=53, 54) | 0.04 scores on a scale | Standard Error 0.49 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AC (n=54, 54) | 0.45 scores on a scale | Standard Error 0.62 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BD (n=53, 54) | 1.07 scores on a scale | Standard Error 0.49 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AE (n=55, 54) | 1.19 scores on a scale | Standard Error 0.69 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BE (n=53, 54) | 0.85 scores on a scale | Standard Error 0.52 |
| Varenicline | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AB (n=54, 54) | 0.34 scores on a scale | Standard Error 0.56 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BE (n=53, 54) | 1.28 scores on a scale | Standard Error 0.44 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AB (n=54, 54) | -0.07 scores on a scale | Standard Error 0.5 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AC (n=54, 54) | 0.37 scores on a scale | Standard Error 0.53 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AD (n=54, 54) | 1.28 scores on a scale | Standard Error 1.03 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AE (n=55, 54) | 0.90 scores on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BC (n=53, 54) | 0.97 scores on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline in the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BD (n=53, 54) | 1.81 scores on a scale | Standard Error 0.92 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-1.09, 1.9]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-1.54, 1.71]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-2.47, 2.6]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-1.57, 2.15]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-2.23, 0.36]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-2.81, 1.33]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-1.78, 0.92]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AD (n=54, 54) | 1.95 scores on a scale | Standard Error 0.41 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BC (n=53, 54) | 3.15 scores on a scale | Standard Error 0.56 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AC (n=54, 54) | 2.69 scores on a scale | Standard Error 0.37 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BD (n=53, 54) | 0.74 scores on a scale | Standard Error 0.47 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AE (n=55, 54) | 1.75 scores on a scale | Standard Error 0.28 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BE (n=53, 54) | 0.73 scores on a scale | Standard Error 0.3 |
| Varenicline | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AB (n=54, 54) | 1.01 scores on a scale | Standard Error 0.32 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BE (n=53, 54) | 0.81 scores on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AB (n=54, 54) | 0.75 scores on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AC (n=54, 54) | 2.16 scores on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AD (n=54, 54) | 1.86 scores on a scale | Standard Error 0.42 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period AE (n=55, 54) | 1.61 scores on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BC (n=53, 54) | 2.65 scores on a scale | Standard Error 0.47 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score | Period BD (n=53, 54) | 0.77 scores on a scale | Standard Error 0.62 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.55, 1.08]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.39, 1.46]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-1.08, 1.25]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.62, 0.9]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.94, 1.95]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-1.57, 1.51]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.91, 0.75]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AD (n=54, 54) | 1.19 scores on a scale | Standard Error 0.29 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BC (n=53, 54) | 2.27 scores on a scale | Standard Error 0.5 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AC (n=54, 54) | 2.28 scores on a scale | Standard Error 0.35 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BD (n=53, 54) | -0.10 scores on a scale | Standard Error 0.35 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AE (n=55, 54) | 1.52 scores on a scale | Standard Error 0.21 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BE (n=53, 54) | 0.40 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AB (n=54, 54) | 1.05 scores on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BE (n=53, 54) | 0.49 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AB (n=54, 54) | 0.83 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AC (n=54, 54) | 1.84 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AD (n=54, 54) | 1.41 scores on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AE (n=55, 54) | 1.50 scores on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BC (n=53, 54) | 1.69 scores on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BD (n=53, 54) | 0.33 scores on a scale | Standard Error 0.53 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.66, 1.1]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.46, 1.35]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-1.16, 0.71]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.68, 0.73]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.79, 1.96]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-1.69, 0.82]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.86, 0.68]
Primary
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.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AD (n=54, 54) | 2.24 scores on a scale | Standard Error 1.75 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BC (n=53, 54) | 0.83 scores on a scale | Standard Error 0.63 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AC (n=54, 54) | 0.82 scores on a scale | Standard Error 0.37 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BD (n=53, 54) | 1.94 scores on a scale | Standard Error 2.27 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AE (n=55, 54) | 1.27 scores on a scale | Standard Error 0.7 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BE (n=53, 54) | 1.00 scores on a scale | Standard Error 0.88 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AB (n=54, 54) | 0.13 scores on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BE (n=53, 54) | -0.13 scores on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AB (n=54, 54) | 0.48 scores on a scale | Standard Error 0.66 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AC (n=54, 54) | 0.72 scores on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AD (n=54, 54) | 0.75 scores on a scale | Standard Error 0.34 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period AE (n=55, 54) | 0.77 scores on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BC (n=53, 54) | 0.22 scores on a scale | Standard Error 0.38 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score | Period BD (n=53, 54) | -0.15 scores on a scale | Standard Error 0.44 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-1.76, 1.06]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.96, 1.17]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-1.94, 4.91]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-1.18, 2.18]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.85, 2.07]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-2.6, 6.79]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.7, 2.96]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AD (n=54, 54) | 0.46 scores on a scale | Standard Error 0.17 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BC (n=53, 54) | 0.82 scores on a scale | Standard Error 0.16 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AC (n=54, 54) | 0.43 scores on a scale | Standard Error 0.1 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BD (n=53, 54) | 0.53 scores on a scale | Standard Error 0.19 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AE (n=55, 54) | 0.32 scores on a scale | Standard Error 0.1 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BE (n=53, 54) | 0.38 scores on a scale | Standard Error 0.11 |
| Varenicline | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AB (n=54, 54) | 0.01 scores on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BE (n=53, 54) | 0.25 scores on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AB (n=54, 54) | 0.01 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AC (n=54, 54) | 0.41 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AD (n=54, 54) | 0.35 scores on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AE (n=55, 54) | 0.24 scores on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BC (n=53, 54) | 0.78 scores on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BD (n=53, 54) | 0.35 scores on a scale | Standard Error 0.24 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.26, 0.27]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.25, 0.29]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.37, 0.58]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.17, 0.34]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.4, 0.48]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.44, 0.78]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.14, 0.4]
Primary
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).
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).
Population: No change from baseline analysis was performed on the OAS-m Suicidality total score as the majority of observations were recorded as 0.
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AD (n=55, 55) | 0.24 scores on a scale | Standard Error 0.36 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BC (n=53, 54) | -0.00 scores on a scale | Standard Error 0.29 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AC (n=55, 55) | -0.04 scores on a scale | Standard Error 0.31 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BD (n=53, 54) | 0.22 scores on a scale | Standard Error 0.41 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AE (n=55, 55) | 0.15 scores on a scale | Standard Error 0.3 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BE (n=54, 54) | -0.05 scores on a scale | Standard Error 0.25 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AB (n=55, 55) | 0.16 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BE (n=54, 54) | -0.43 scores on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AB (n=55, 55) | -0.69 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AC (n=55, 55) | -0.89 scores on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AD (n=55, 55) | -1.00 scores on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period AE (n=55, 55) | -0.68 scores on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BC (n=53, 54) | -0.52 scores on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale | Period BD (n=53, 54) | -0.65 scores on a scale | Standard Error 0.19 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.02, 1.72]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [0.16, 1.54]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [0.39, 2.08]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [0.14, 1.52]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.06, 1.09]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [0.05, 1.7]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.12, 0.88]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AD (n=55, 55) | 0.10 scores on a scale | Standard Error 0.18 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BC (n=53, 54) | 0.02 scores on a scale | Standard Error 0.22 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AC (n=55, 55) | 0.03 scores on a scale | Standard Error 0.17 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BD (n=53, 54) | 0.07 scores on a scale | Standard Error 0.22 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AE (n=55, 55) | -0.01 scores on a scale | Standard Error 0.15 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BE (n=54, 54) | -0.14 scores on a scale | Standard Error 0.18 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AB (n=55, 55) | 0.14 scores on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BE (n=54, 54) | -0.02 scores on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AB (n=55, 55) | -0.09 scores on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AC (n=55, 55) | -0.18 scores on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AD (n=55, 55) | -0.11 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period AE (n=55, 55) | -0.03 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BC (n=53, 54) | -0.07 scores on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale | Period BD (n=53, 54) | -0.02 scores on a scale | Standard Error 0.15 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.2, 0.65]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.17, 0.58]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.23, 0.65]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.37, 0.41]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.41, 0.59]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.44, 0.63]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.58, 0.34]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AD (n=55, 55) | 0.56 scores on a scale | Standard Error 0.27 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BC (n=53, 54) | 0.51 scores on a scale | Standard Error 0.27 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AC (n=55, 55) | 0.50 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BD (n=53, 54) | 0.49 scores on a scale | Standard Error 0.32 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AE (n=55, 55) | 0.44 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BE (n=54, 54) | 0.32 scores on a scale | Standard Error 0.23 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AB (n=55, 55) | 0.38 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BE (n=54, 54) | 0.23 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AB (n=55, 55) | -0.24 scores on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AC (n=55, 55) | -0.24 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AD (n=55, 55) | -0.10 scores on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period AE (n=55, 55) | 0.00 scores on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BC (n=53, 54) | 0.03 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale | Period BD (n=53, 54) | 0.10 scores on a scale | Standard Error 0.14 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [0, 1.24]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [0.18, 1.29]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [0.02, 1.3]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.19, 1.05]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.09, 1.05]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.28, 1.06]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.47, 0.65]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AD (n=55, 55) | -0.58 scores on a scale | Standard Error 0.26 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BC (n=53, 54) | 0.37 scores on a scale | Standard Error 0.32 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AC (n=55, 55) | -0.29 scores on a scale | Standard Error 0.28 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BD (n=53, 54) | -0.20 scores on a scale | Standard Error 0.29 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AE (n=55, 55) | -0.32 scores on a scale | Standard Error 0.27 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BE (n=54, 54) | -0.16 scores on a scale | Standard Error 0.29 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AB (n=55, 55) | -0.14 scores on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BE (n=54, 54) | -0.26 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AB (n=55, 55) | -0.65 scores on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AC (n=55, 55) | -0.83 scores on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AD (n=55, 55) | -0.76 scores on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period AE (n=55, 55) | -0.59 scores on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BC (n=53, 54) | -0.22 scores on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale | Period BD (n=53, 54) | -0.13 scores on a scale | Standard Error 0.3 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.29, 1.32]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.17, 1.25]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.55, 0.92]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.46, 0.99]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.19, 1.37]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.91, 0.76]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.65, 0.85]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AD (n=55, 55) | 0.31 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BC (n=53, 54) | -0.01 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AC (n=55, 55) | 0.15 scores on a scale | Standard Error 0.25 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BD (n=53, 54) | 0.06 scores on a scale | Standard Error 0.23 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AE (n=55, 55) | 0.01 scores on a scale | Standard Error 0.24 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BE (n=54, 54) | -0.35 scores on a scale | Standard Error 0.19 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AB (n=55, 55) | 0.30 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BE (n=54, 54) | -0.58 scores on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AB (n=55, 55) | -0.31 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AC (n=55, 55) | -0.26 scores on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AD (n=55, 55) | -0.18 scores on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period AE (n=55, 55) | -0.43 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BC (n=53, 54) | -0.10 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale | Period BD (n=53, 54) | -0.16 scores on a scale | Standard Error 0.29 |
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.26, 1.22]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.18, 1.06]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.58, 0.78]
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.15, 1.39]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.24, 1.07]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.48, 0.92]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.26, 0.72]
Primary
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).
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).
Population: Full analysis set (FAS): All randomized subjects with at least 1 dose of study drug and at least 1 post-baseline neuropsychiatric evaluation or Minnesota Nicotine Withdrawal Scale (MNWS) obtained; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AD (n=55, 55) | 0.95 scores on a scale | Standard Error 0.43 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BC (n=53, 54) | 0.48 scores on a scale | Standard Error 0.35 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AC (n=55, 55) | 0.30 scores on a scale | Standard Error 0.35 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BD (n=53, 54) | 1.07 scores on a scale | Standard Error 0.47 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AE (n=55, 55) | 0.72 scores on a scale | Standard Error 0.36 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BE (n=54, 54) | 0.59 scores on a scale | Standard Error 0.37 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AB (n=55, 55) | 0.06 scores on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BE (n=54, 54) | 0.96 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AB (n=55, 55) | -0.66 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AC (n=55, 55) | -0.17 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AD (n=55, 55) | 0.03 scores on a scale | Standard Error 0.41 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period AE (n=55, 55) | 0.22 scores on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BC (n=53, 54) | 0.91 scores on a scale | Standard Error 0.31 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD) | Period BD (n=53, 54) | 1.04 scores on a scale | Standard Error 0.39 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.33, 1.77]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.5, 1.43]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.27, 2.11]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.52, 1.53]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-1.35, 0.5]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-1.18, 1.24]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-1.37, 0.63]
Primary
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).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AD (n=55, 55) | -3.30 scores on a scale | Standard Error 1.18 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BC (n=53, 54) | -1.49 scores on a scale | Standard Error 0.81 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AC (n=55, 55) | -1.34 scores on a scale | Standard Error 0.87 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BD (n=53, 54) | -3.22 scores on a scale | Standard Error 1.25 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AE (n=55, 55) | -2.80 scores on a scale | Standard Error 1 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BE (n=54, 54) | -2.28 scores on a scale | Standard Error 1.02 |
| Varenicline | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AB (n=55, 55) | 0.16 scores on a scale | Standard Error 0.86 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BE (n=54, 54) | -3.37 scores on a scale | Standard Error 1.04 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AB (n=55, 55) | 0.98 scores on a scale | Standard Error 0.75 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AC (n=55, 55) | -1.15 scores on a scale | Standard Error 0.75 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AD (n=55, 55) | -1.14 scores on a scale | Standard Error 0.97 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period AE (n=55, 55) | -1.82 scores on a scale | Standard Error 0.91 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BC (n=53, 54) | -3.44 scores on a scale | Standard Error 0.83 |
| Placebo | Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale | Period BD (n=53, 54) | -3.22 scores on a scale | Standard Error 1.11 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-3.07, 1.43]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-2.47, 2.08]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-5.19, 0.89]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-3.67, 1.7]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.36, 4.26]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-3.32, 3.3]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-1.8, 3.97]
Primary
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).
Time frame: Baseline B (Week 2) to Week 4 (Period BC)
Population: No change from baseline analysis was performed on the SDAS total score as the majority of observations were recorded as 0.
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale
The MNWS increased appetite subscale contains 1 item (increased appetite) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no increased appetite) to 4 (extreme increased appetite).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AD (n=54, 54) | 0.11 scores on a scale | Standard Error 0.09 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BC (n=53, 54) | -0.03 scores on a scale | Standard Error 0.07 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AC (n=54, 54) | 0.10 scores on a scale | Standard Error 0.05 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BD (n=53, 54) | -0.01 scores on a scale | Standard Error 0.09 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AE (n=55, 54) | -0.00 scores on a scale | Standard Error 0.05 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BE (n=53, 54) | -0.10 scores on a scale | Standard Error 0.04 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AB (n=54, 54) | 0.14 scores on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BE (n=53, 54) | -0.03 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AB (n=54, 54) | 0.02 scores on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AC (n=54, 54) | 0.12 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AD (n=54, 54) | 0.15 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period AE (n=55, 54) | 0.04 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BC (n=53, 54) | 0.16 scores on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale | Period BD (n=53, 54) | 0.15 scores on a scale | Standard Error 0.1 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.05, 0.28]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.19, 0.14]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.29, 0.22]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.2, 0.13]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.4, 0.01]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.42, 0.1]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.22, 8]
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale
The MNWS insomnia domain subscale contains 2 items (difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average of the 2 items and ranged from 0 (no insomnia) to 4 (extreme insomnia).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AD (n=54, 54) | 0.04 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BC (n=53, 54) | 0.14 scores on a scale | Standard Error 0.07 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AC (n=54, 54) | 0.15 scores on a scale | Standard Error 0.04 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BD (n=53, 54) | -0.04 scores on a scale | Standard Error 0.05 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AE (n=55, 54) | 0.06 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BE (n=53, 54) | -0.06 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AB (n=54, 54) | 0.07 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BE (n=53, 54) | -0.01 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AB (n=54, 54) | 0.12 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AC (n=54, 54) | 0.17 scores on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AD (n=54, 54) | 0.10 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period AE (n=55, 54) | 0.13 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BC (n=53, 54) | 0.09 scores on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale | Period BD (n=53, 54) | 0.01 scores on a scale | Standard Error 0.06 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.2, 0.09]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.15, 0.12]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.15, 0.04]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.2, 0.04]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.17, 0.27]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.21, 0.1]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.17, 0.07]
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale
The MNWS negative affect domain subscale contains 4 items (depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average from all 4 items and ranged from 0 (no negative affect) to 4 (extreme negative affect).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AD (n=54, 54) | 0.07 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BC (n=53, 54) | 0.07 scores on a scale | Standard Error 0.05 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AC (n=54, 54) | 0.10 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BD (n=53, 54) | -0.01 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AE (n=55, 54) | 0.05 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BE (n=53, 54) | -0.02 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AB (n=54, 54) | 0.06 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BE (n=53, 54) | 0.03 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AB (n=54, 54) | 0.01 scores on a scale | Standard Error 0.02 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AC (n=54, 54) | 0.09 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AD (n=54, 54) | 0.03 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period AE (n=55, 54) | 0.07 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BC (n=53, 54) | 0.15 scores on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale | Period BD (n=53, 54) | 0.02 scores on a scale | Standard Error 0.05 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.03, 0.12]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.08, 0.09]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.04, 0.11]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.08, 0.05]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.22, 0.06]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.14, 0.09]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.11, 0.02]
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale
The MNWS restlessness subscale contains 1 item (restlessness) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no restlessness) to 4 (extreme restlessness).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AD (n=54, 54) | 0.09 scores on a scale | Standard Error 0.04 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BC (n=53, 54) | 0.07 scores on a scale | Standard Error 0.05 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AC (n=54, 54) | 0.10 scores on a scale | Standard Error 0.04 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BD (n=53, 54) | 0.03 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AE (n=55, 54) | 0.03 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BE (n=53, 54) | -0.04 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AB (n=54, 54) | 0.06 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BE (n=53, 54) | -0.03 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AB (n=54, 54) | 0.08 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AC (n=54, 54) | 0.11 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AD (n=54, 54) | 0.04 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period AE (n=55, 54) | 0.05 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BC (n=53, 54) | 0.08 scores on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale | Period BD (n=53, 54) | -0.03 scores on a scale | Standard Error 0.01 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.12, 0.08]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.12, 0.08]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.04, 0.14]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.07, 0.04]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.15, 0.13]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [0.01, 0.1]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.08, 0.04]
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score
The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Total scores were the average score for all 9 items and ranged from 0 (no withdrawal symptoms) to 4 (extreme withdrawal symptoms).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AD (n=54, 54) | 0.07 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BC (n=53, 54) | -0.04 scores on a scale | Standard Error 0.04 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AC (n=54, 54) | 0.10 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BD (n=53, 54) | -0.08 scores on a scale | Standard Error 0.03 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AE (n=55, 54) | -0.01 scores on a scale | Standard Error 0.02 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BE (n=53, 54) | -0.15 scores on a scale | Standard Error 0.01 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AB (n=54, 54) | 0.13 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BE (n=53, 54) | -0.05 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AB (n=54, 54) | 0.05 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AC (n=54, 54) | 0.11 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AD (n=54, 54) | 0.05 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period AE (n=55, 54) | 0.04 scores on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BC (n=53, 54) | 0.10 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score | Period BD (n=53, 54) | 0.02 scores on a scale | Standard Error 0.04 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.04, 0.19]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.11, 0.08]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.06, 0.09]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.11, 0.02]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.27, -0.01]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.21, 0.01]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.17, -0.03]
Secondary
Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale
The MNWS urge to smoke subscale contains 1 item (urge to smoke) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no urge to smoke) to 4 (extreme urge to smoke).
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AD (n=54, 54) | -2.17 scores on a scale | Standard Error 0.12 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BC (n=53, 54) | -1.59 scores on a scale | Standard Error 0.12 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AC (n=54, 54) | -1.40 scores on a scale | Standard Error 0.09 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BD (n=53, 54) | -1.66 scores on a scale | Standard Error 0.14 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AE (n=55, 54) | -1.90 scores on a scale | Standard Error 0.09 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BE (n=53, 54) | -1.56 scores on a scale | Standard Error 0.1 |
| Varenicline | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AB (n=54, 54) | -0.60 scores on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BE (n=53, 54) | -1.29 scores on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AB (n=54, 54) | -0.29 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AC (n=54, 54) | -0.97 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AD (n=54, 54) | -2.03 scores on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period AE (n=55, 54) | -1.55 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BC (n=53, 54) | -1.14 scores on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale | Period BD (n=53, 54) | -1.58 scores on a scale | Standard Error 0.15 |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.95% CI: [-0.58, -0.02]
Comparison: Period AC: Difference varenicline versus placebo.95% CI: [-0.69, -0.19]
Comparison: Period AD: Difference varenicline versus placebo.95% CI: [-0.47, 0.2]
Comparison: Period AE: Difference varenicline versus placebo.95% CI: [-0.61, -0.09]
Comparison: Period BC: Difference varenicline versus placebo.95% CI: [-0.83, -0.07]
Comparison: Period BD: Difference varenicline versus placebo.95% CI: [-0.5, 0.34]
Comparison: Period BE: Difference varenicline versus placebo.95% CI: [-0.57, 0.02]
Secondary
Change From Baseline in the Number of Cigarettes Smoked Per Day
Time frame: Baseline (Week 0) to Week 2
Population: FAS; (n)=number of subjects with at least 1 dose of study drug and an observation for a given day.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 2 (n=55, 54) | -0.1 cigarettes smoked per day | Standard Deviation 3.6 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 3 (n=55, 54) | -0.6 cigarettes smoked per day | Standard Deviation 4.1 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 4 (n=55, 54) | -1.8 cigarettes smoked per day | Standard Deviation 5 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 5 (n=55, 54) | -1.0 cigarettes smoked per day | Standard Deviation 5.2 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 6 (n=54, 54) | -1.3 cigarettes smoked per day | Standard Deviation 5.9 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 7 (n=54, 54) | -1.8 cigarettes smoked per day | Standard Deviation 4.9 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 8 (n=54, 54) | -1.7 cigarettes smoked per day | Standard Deviation 5 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 9 (n=52, 54) | -1.0 cigarettes smoked per day | Standard Deviation 5.1 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 10 (n=52, 54) | -1.7 cigarettes smoked per day | Standard Deviation 5.7 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 11 (n=53, 54) | -1.8 cigarettes smoked per day | Standard Deviation 5.3 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 12 (n=53, 54) | -0.7 cigarettes smoked per day | Standard Deviation 6.6 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 13 (n=53, 54) | -1.4 cigarettes smoked per day | Standard Deviation 5.6 |
| Varenicline | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 14 (n=36, 38) | -17.2 cigarettes smoked per day | Standard Deviation 8.6 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 12 (n=53, 54) | -0.2 cigarettes smoked per day | Standard Deviation 6.3 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 9 (n=52, 54) | 0.1 cigarettes smoked per day | Standard Deviation 4.2 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 3 (n=55, 54) | 0.0 cigarettes smoked per day | Standard Deviation 3.9 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 14 (n=36, 38) | -15.7 cigarettes smoked per day | Standard Deviation 6.6 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 4 (n=55, 54) | -0.3 cigarettes smoked per day | Standard Deviation 3.7 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 10 (n=52, 54) | -0.4 cigarettes smoked per day | Standard Deviation 6.1 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 5 (n=55, 54) | -0.4 cigarettes smoked per day | Standard Deviation 4 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 13 (n=53, 54) | -0.1 cigarettes smoked per day | Standard Deviation 6.1 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 6 (n=54, 54) | 0.1 cigarettes smoked per day | Standard Deviation 4.5 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 11 (n=53, 54) | -0.4 cigarettes smoked per day | Standard Deviation 6.3 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 7 (n=54, 54) | -0.3 cigarettes smoked per day | Standard Deviation 5 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 2 (n=55, 54) | -0.2 cigarettes smoked per day | Standard Deviation 3.7 |
| Placebo | Change From Baseline in the Number of Cigarettes Smoked Per Day | Day 8 (n=54, 54) | 0.4 cigarettes smoked per day | Standard Deviation 4.3 |
Secondary
Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score
The BIS-11 is designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Total score ranged from 30 (less impulsive) to 120 (more impulsive). Participants exceeding the threshold had a BIS-11 total score more than or equal to 70 out of 120. BIS-11 total scores of more than or equal to 70 could reflect clinically important and potentially pathological impulsivity.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AD (n=54, 54) | 1 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BC (n=53, 54) | 1 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AC (n=54, 54) | 1 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BD (n=53, 54) | 1 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AE (n=55, 54) | 5 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BE (n=54, 54) | 5 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AB (n=54, 54) | 1 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BE (n=54, 54) | 5 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AB (n=54, 54) | 0 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AC (n=54, 54) | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AD (n=54, 54) | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period AE (n=55, 54) | 5 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BC (n=53, 54) | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Barratt Impulsiveness Scale - Version 11 (BIS-11): Total Score | Period BD (n=53, 54) | 2 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0, 5.6]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0, 5.6]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 3.6]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0, 5.7]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0, 5.7]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 3.7]
Secondary
Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score
HAM-A measures treatment-related changes in generalized anxiety symptoms. Total scores ranged from 0 (not affected) to 56 (very severely affected). Participants exceeding the threshold had a HAM-A total score of more than or equal to 14 out of 56. HAM-A total scores of more than or equal to 14 may reflect clinically noteworthy levels of anxiety.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AD (n=54, 54) | 12 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BC (n=53, 54) | 9 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AC (n=54, 54) | 9 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BD (n=53, 54) | 12 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AE (n=55, 54) | 16 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BE (n=54, 54) | 16 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AB (n=54, 54) | 0 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BE (n=54, 54) | 9 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AB (n=54, 54) | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AC (n=54, 54) | 7 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AD (n=54, 54) | 7 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period AE (n=55, 54) | 10 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BC (n=53, 54) | 6 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Hamilton Anxiety Scale (HAM-A): Total Score | Period BD (n=53, 54) | 6 participants |
Comparison: Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 3.9]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.7, 5.3]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.7, 4.4]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 5]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.8, 6.8]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.8, 5.3]
Secondary
Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score
The MADRS measures the overall severity of depressive symptoms. Total score ranged from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Participants exceeding the threshold had a MADRS total score of more than 14 out of 60. MADRS total scores exceeding 14 may represent clinically notable effective symptomatology.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively. Statistical analyses were not performed for Period AB due to the small number of participants exceeding the threshold.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AD (n=54, 54) | 8 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BC (n=53, 54) | 5 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AC (n=54, 54) | 7 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BD (n=53, 54) | 6 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AE (n=55, 54) | 11 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BE (n=54, 54) | 9 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AB (n=54, 54) | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BE (n=54, 54) | 8 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AB (n=54, 54) | 0 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AC (n=54, 54) | 3 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AD (n=54, 54) | 3 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period AE (n=55, 54) | 8 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BC (n=53, 54) | 3 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score | Period BD (n=53, 54) | 3 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.6, 10.4]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.7, 11.8]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 3.9]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 7.8]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 9.2]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 3.2]
Secondary
Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score
The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Aggression total score ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week. Participants exceeding the threshold had an OAS-m Aggression total score of more than or equal to 3 out of any number with no upper limit depending on the frequency of agressive behaviour in a week. OAS-m Aggression total scores of more than or equal to 3 reflect clinically important aggression.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AB (n=54, 54) | 9 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AC (n=54, 54) | 20 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AD (n=54, 54) | 21 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AE (n=55, 54) | 28 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BC (n=53, 54) | 15 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BD (n=53, 54) | 18 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BE (n=54, 54) | 27 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AB (n=54, 54) | 6 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BC (n=53, 54) | 19 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AC (n=54, 54) | 21 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BE (n=54, 54) | 30 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AD (n=54, 54) | 23 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period BD (n=53, 54) | 21 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Agression Total Score | Period AE (n=55, 54) | 31 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 4.9]
Comparison: Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 2]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.8]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.6]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 1.6]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.8]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.7]
Secondary
Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score
The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Irritability total score ranged from 0 (no irritability) to 10 (extreme irritability). Participants exceeding the threshold had an OAS-m Irritability total score of more than or equal to 2 out of 10. OAS-m Irritability total scores of more than or equal to 2 reflect clinically important irritability.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AD (n=54, 54) | 36 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BC (n=53, 54) | 31 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AC (n=54, 54) | 32 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BD (n=53, 54) | 35 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AE (n=55, 54) | 41 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BE (n=54, 54) | 40 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AB (n=54, 54) | 10 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BE (n=54, 54) | 38 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AB (n=54, 54) | 11 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AC (n=54, 54) | 34 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AD (n=54, 54) | 36 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period AE (n=55, 54) | 39 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BC (n=53, 54) | 31 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score | Period BD (n=53, 54) | 33 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 2.3]
Comparison: Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.9]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 2.2]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 2.6]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 2.3]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.6, 2.7]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.5, 2.8]
Secondary
Number of Participants Exceeding Thresholds for the Overt Aggression Scale (Modified) (OAS-m): Suicidality Total Score
The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Suicidality total score ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency). No threshold criterion was determined for 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).
Population: The number of participants above the threshold for the OAS-m Suicidality total score was not analyzed as the majority of observations were recorded as 0.
Secondary
Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score
POMS total mood disturbance (TMD) summary results were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance). Participants exceeding the threshold had an increase from baseline of 1 standard deviation of the TMD baseline T-score plus 1 or more.
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).
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AD (n=55, 55) | 37 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BC (n=53, 54) | 27 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AC (n=55, 55) | 32 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BD (n=53, 54) | 30 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AE (n=55, 55) | 38 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BE (n=54, 54) | 32 participants |
| Varenicline | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AB (n=55, 55) | 14 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BE (n=54, 54) | 38 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AB (n=55, 55) | 11 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AC (n=55, 55) | 35 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AD (n=55, 55) | 38 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period AE (n=55, 55) | 38 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BC (n=53, 54) | 33 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score | Period BD (n=53, 54) | 36 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.6, 3.3]
Comparison: Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 1.7]
Comparison: Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 2.1]
Comparison: Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.4, 2.2]
Comparison: Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 1.4]
Comparison: Period BD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 1.4]
Comparison: Period BE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.3, 1.4]
Secondary
Number of Participants Exceeding Thresholds for the Social Dysfunction and Aggression Scale (SDAS): Total Score
SDAS total scores ranged from 0 (not present) to 44 (extremely severe). Participants exceeding the threshold had a SDAS total score of more than 6 out of 44.
Time frame: Baseline B (Week 2) to Week 4 (Period BC)
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants Exceeding Thresholds for the Social Dysfunction and Aggression Scale (SDAS): Total Score | 2 participants |
| Placebo | Number of Participants Exceeding Thresholds for the Social Dysfunction and Aggression Scale (SDAS): Total Score | 1 participants |
Comparison: There was no hypothesis testing or power calculation in this study. Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.95% CI: [0.2, 23.6]
Secondary
Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation)
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
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 6 (n=55, 55) | 23 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 10 (n=55, 55) | 17 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 8 (n=55, 55) | 21 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 11 (n=55, 55) | 20 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 7 (n=55, 55) | 20 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 12 (n=55, 55) | 19 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 9 (n=55, 55) | 25 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 13 (n=55, 55) | 23 participants |
| Varenicline | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 5 (n=55, 55) | 19 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 13 (n=55, 55) | 15 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 5 (n=55, 55) | 16 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 6 (n=55, 55) | 12 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 7 (n=55, 55) | 17 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 8 (n=55, 55) | 15 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 9 (n=55, 55) | 14 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 10 (n=55, 55) | 17 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 11 (n=55, 55) | 18 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Abstinence (Smoking Cessation) | Week 12 (n=55, 55) | 15 participants |
Secondary
Number of Participants With Carbon Monoxide Confirmed Daily Smoking Cessation
Participants who reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory, which was used to collect the information of cigarette or other nicotine use during the study) and who did not have carbon monoxide of more than 10 parts per million at any time from Week 9 to Week 12
Time frame: Week 9 to Week 12
Population: FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants With Carbon Monoxide Confirmed Daily Smoking Cessation | 16 participants |
| Placebo | Number of Participants With Carbon Monoxide Confirmed Daily Smoking Cessation | 10 participants |