Smoking Cessation
Conditions
Keywords
smoking cessation in adolescents
Brief summary
The study is designed to see if varenicline combined with age appropriate (adolescent) smoking cessation counseling will help teens quit smoking.
Interventions
Oral Varenicline 1mg BID, or 1/2 that dose (0.5mg BID) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52
DRUGVarenicline 0.5mg BID
Oral Varenicline 0.5mg BID, or 1/2 that dose (0.5 QD) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52
DRUGPlacebo
Oral placebo for twelve weeks,follow-up through Week 52
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Healthy male and female subjects between the ages of 12 and 19, inclusive. * Subjects smoking at least an average of 5 cigarettes per day, motivated to stop smoking, * Subjects must have at least one prior failed attempt to quit smoking.
Exclusion criteria
* Subjects with history, current diagnosis, or treatment of major depression disorder, anxiety disorders, panic disorder, hostility or aggression disorder, perceptual/thinking disturbances, mania, psychosis, bipolar disorder, personality disorder, eating disorder or severe emotional problems (in the past year). * Subjects with a prior suicide attempt: subjects hospitalized within the past 12 months due to suicidal ideation or suicidal behavior; subjects considered to have serious suicidal ideation or suicidal behavior in the past 12 months; active suicidal ideation or behavior identified at the screening or baseline visit. * Evidence of alcohol and substance abuse/dependence (other than nicotine) within 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12 | Week 9 through Week 12 | The percentage of participants who, at each visit from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory) and at each of these visits were confirmed to have quit based on urine cotinine less than 200 nanograms/milliliter (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Weeks 12, 24 and 52 | The percentage of participants who reported no smoking and no use of other nicotine-containing products (treatment phase) or tobacco products (non-treatment phase) on the Nicotine Use Inventory in the 7 days prior to the study visits or telephone contacts at Week 12,24 and 52. |
| Daily Number of Cigarettes Smoked at Baseline | Baseline | The average number of cigarettes smoked per day in the past 7 days reported at the baseline visit. |
| Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Baseline, Weeks 12, 24, and 52 | The reduction in the number of the cigarettes smoked was calculated by subtracting the reported average number of cigarettes smoked per day in the past 7 days at Weeks 12, 24 and 52 from the average number of cigarettes smoked per day in the past 7 days reported at the baseline visit. |
| Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 24; Week 9 through Week 52 | The percentage of participants who, at each visit from Week 9 to 52 (inclusive), reported no smoking and no use of other nicotine-containing products (Weeks 9-12) or tobacco products (Weeks 13-52) since the last study visit/last contact (on the Nicotine Use Inventory) and at any of the study visits were confirmed to have quit based on urine cotinine less than 200 ng/mL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52 | Hospital Anxiety and Depression Scale Depression subscale (HADS-D) consists of 7 items that were assessed on a scale of 0 = no depression to 3 = severe feeling of depression. Total HADS-D subscale score range from 0 = no depression to 21 = severe feeling of depression; higher scores indicated a greater intensity of depression. |
| Number of Participants With Laboratory Abnormalities | Baseline up to Week 12 | Criteria for laboratory abnormalities: Lymphocytes Absolute (Abs), Lymphocytes percentage (%), Total Neutrophils (Abs), Neutrophils %: \<0.8\*LLN or \>1.2\*ULN; Basophils (Abs), Basophils %Eosinophils (Abs), Eosinophils %, Monocytes (Abs), Monocytes %:\> 1.2\*ULN; Total Bilirubin milligram per deciliter (mg/dl) \>1.5\*ULN; alanine aminotransferase: \>3.0\*ULN; Blood urea nitrogen, Creatinine: \>1.3\*ULN; Uric acid :\> 1.2\*ULN. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | First dose up to last dose (up-to Week 12) plus 30 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious AEs and SAEs. |
| Change From Baseline in Pulse Rate at Week 12 | Baseline, Week 12 | Measurement of pulse rate included supine, sitting and standing pulse rate. Pulse rate was taken after participants rested in a sitting position for 5 minutes. Pulse rate was recorded after participants had been supine for approximately 5 minutes and then immediately upon standing. |
| Change From Baseline in Blood Pressure (BP) at Week 12 | Baseline, Week 12 | Measurement of BP included supine and sitting systolic BP, standing systolic BP, supine and sitting diastolic BP and standing diastolic BP. Blood pressure was taken after participants rested in a sitting position for 5 minutes. BP was recorded after participants had been supine for approximately 5 minutes, and then orthostatic blood pressure was recorded immediately when the participant stood. |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | First dose up to last dose (up-to Week 12) plus 30 days | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug Varenicline was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious AEs and SAEs. |
| Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | First dose up to last dose (up-to Week 12) plus 30 days | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE: AE causing: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Solicited AEs collected by semi-structured NAEI inquiring about AEs: depression, anxiety, delusions, hallucinations, paranoia, psychosis, mania, panic, agitation, dissociative states, feeling abnormal, hostility, aggression and homicidal ideation. If a participant had a positive response to any item on the NAEI, investigator determined if it met criteria AE criteria. |
| Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening, Baseline, Week 1 up to Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (last follow-up [FU]) | The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories);was an interview-based instrument to systematically assess suicidal ideation and suicidal behavior.C-SSRS assessed whether participant experienced any of the following:completed suicide;suicide attempt(response of Yes on actual attempt);preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior,aborted attempt or interrupted attempt),suicidal ideation (Yes on wish to be dead,non-specific active suicidal thoughts,active suicidal ideation with methods without intent to act or some intent to act,without specific plan or with specific plan and intent,any self-injurious behavior with no suicidal intent (Yes on Has participant engaged in non-suicidal self-injurious behavior).Here,number of participants with positive response (response of yes) to suicidal behavior or/and Ideation,any non-suicidal self-injurious behavior were reported. |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52 | The HADS is a self-administered questionnaire measuring anxiety. Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) consisted of 7 items that were assessed on a scale of 0 = no anxiety to 3 = severe feeling of anxiety. Total HADS-A subscale score range from 0 = no anxiety to 21 = severe anxiety; higher scores indicated more severe anxiety. |
Countries
Canada, Georgia, Russia, South Korea, Taiwan, United States
Participant flow
Pre-assignment details
This study consisted of 3 phases: Screening (3 weeks before first dose of study drug); treatment (from Week 2 to Week 12 after a 2-week titration) and non-treatment follow-up (Week 13 through Week 52).
Participants by arm
| Arm | Count |
|---|---|
| Varenicline High Dose Participants received 2 tablets of Varenicline 0.5 milligram (mg) (total dose 1 mg) orally, twice daily from Week 2 to Week 12 after a 2-week titration. Participants with a body weight less than or equal to (\<=) 55 kilograms (kg) had Varenicline dose reduced by half, and received one tablet of Varenicline 0.5 mg and one matching placebo tablet orally, twice daily from Week 2 to Week 12 after a 2-week titration. | 108 |
| Varenicline Low Dose Participants received one tablet of Varenicline 0.5 mg and one matching placebo tablet orally, twice daily from Week 2 to Week 12 after a 2-week titration. Participants with a body weight \<= 55 kg had Varenicline dose reduced by half and received one tablet of Varenicline 0.5 mg and one matching placebo tablet orally, in the morning and 2 tablets of matching placebo orally, in the evening from Week 2 to Week 12 after a 2-week titration. | 100 |
| Placebo Participants received 2 tablets of placebo (matched to Varenicline) orally, twice daily from Week 2 to Week 12 after a 2-week titration. | 99 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 3 |
| Overall Study | Entrance criteria not met | 0 | 0 | 2 |
| Overall Study | Insufficient clinical response | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 21 | 17 | 20 |
| Overall Study | Other | 9 | 6 | 11 |
| Overall Study | Protocol Violation | 2 | 0 | 2 |
| Overall Study | Randomized but not treated | 1 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 10 | 7 |
Baseline characteristics
| Characteristic | Varenicline High Dose | Varenicline Low Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 16.0 years STANDARD_DEVIATION 2 | 16.0 years STANDARD_DEVIATION 1.7 | 15.8 years STANDARD_DEVIATION 1.8 | 15.9 years STANDARD_DEVIATION 1.8 |
| Race/Ethnicity, Customized Asian | 16 Participants | 18 Participants | 19 Participants | 53 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 9 Participants | 5 Participants | 23 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 81 Participants | 73 Participants | 74 Participants | 228 Participants |
| Sex: Female, Male Female | 38 Participants | 37 Participants | 36 Participants | 111 Participants |
| Sex: Female, Male Male | 70 Participants | 63 Participants | 63 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 100 | 0 / 99 |
| other Total, other adverse events | 65 / 108 | 53 / 100 | 51 / 99 |
| serious Total, serious adverse events | 3 / 108 | 1 / 100 | 1 / 99 |
Outcome results
Primary
4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12
The percentage of participants who, at each visit from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory) and at each of these visits were confirmed to have quit based on urine cotinine less than 200 nanograms/milliliter (ng/mL).
Time frame: Week 9 through Week 12
Population: The full analysis set included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline High Dose | 4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12 | 20.2 percentage of participants |
| Varenicline Low Dose | 4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12 | 27.2 percentage of participants |
| Placebo | 4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12 | 18.0 percentage of participants |
Comparison: Odds ratios and p-values were obtained from a logistic regression model with terms treatment, age strata, body weight strata and pooled center. A testing order was used to control type I error. 1mg Varenicline twice daily group was tested against placebo first, and if statistically significant difference was observed, the 0.5 mg Varenicline twice daily group was tested against placebo.p-value: 0.633795% CI: [0.59, 2.37]Regression, Logistic
Comparison: Odds ratios and p-values were obtained from a logistic regression model with terms treatment, age strata, body weight strata and pooled center. A testing order was used to control type I error. 1mg Varenicline twice daily group was tested against placebo first, and if statistically significant difference was observed, the 0.5 mg Varenicline twice daily group was tested against placebo.p-value: 0.111495% CI: [0.88, 3.39]Regression, Logistic
Secondary
Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52
The reduction in the number of the cigarettes smoked was calculated by subtracting the reported average number of cigarettes smoked per day in the past 7 days at Weeks 12, 24 and 52 from the average number of cigarettes smoked per day in the past 7 days reported at the baseline visit.
Time frame: Baseline, Weeks 12, 24, and 52
Population: The full analysis set included all randomized participants. The longitudinal model included all participants regardless of observed visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline High Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 24 | -6.93 cigarettes smoked per day | Standard Error 0.44 |
| Varenicline High Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 12 | -8.56 cigarettes smoked per day | Standard Error 0.43 |
| Varenicline High Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 52 | -6.80 cigarettes smoked per day | Standard Error 0.45 |
| Varenicline Low Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 24 | -7.31 cigarettes smoked per day | Standard Error 0.45 |
| Varenicline Low Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 12 | -8.20 cigarettes smoked per day | Standard Error 0.44 |
| Varenicline Low Dose | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 52 | -7.74 cigarettes smoked per day | Standard Error 0.46 |
| Placebo | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 12 | -8.01 cigarettes smoked per day | Standard Error 0.46 |
| Placebo | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 52 | -6.98 cigarettes smoked per day | Standard Error 0.48 |
| Placebo | Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52 | Change at Week 24 | -6.59 cigarettes smoked per day | Standard Error 0.48 |
Comparison: Week 12: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.35495% CI: [-1.69, 0.6]Longitudinal repeated measures model
Comparison: Week 12: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.757495% CI: [-1.35, 0.98]Longitudinal repeated measures model
Comparison: Week 24: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.567695% CI: [-1.53, 0.84]Longitudinal repeated measures model
Comparison: Week 24: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.235695% CI: [-1.92, 0.47]Longitudinal repeated measures model
Comparison: Week 52: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.77395% CI: [-1.03, 1.38]Longitudinal repeated measures model
Comparison: Week 52: Analysis was performed using longitudinal repeated measures model with the change from baseline average number of Cigarettes Smoked as the dependent variable, including terms treatment, visit, age strata, body weight strata, pooled center, baseline measure and treatment by visit interaction.p-value: 0.216695% CI: [-1.99, 0.45]Longitudinal repeated measures model
Secondary
Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52
The percentage of participants who, at each visit from Week 9 to 52 (inclusive), reported no smoking and no use of other nicotine-containing products (Weeks 9-12) or tobacco products (Weeks 13-52) since the last study visit/last contact (on the Nicotine Use Inventory) and at any of the study visits were confirmed to have quit based on urine cotinine less than 200 ng/mL.
Time frame: Week 9 through Week 24; Week 9 through Week 52
Population: The full analysis set included all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline High Dose | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 24 | 10.1 percentage of participants |
| Varenicline High Dose | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 52 | 8.3 percentage of participants |
| Varenicline Low Dose | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 24 | 24.3 percentage of participants |
| Varenicline Low Dose | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 52 | 20.4 percentage of participants |
| Placebo | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 24 | 13.0 percentage of participants |
| Placebo | Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52 | Week 9 through Week 52 | 9.0 percentage of participants |
Comparison: Week 9 through Week 24: Odds ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center, age strata and body weight strata.p-value: 0.613395% CI: [0.34, 1.9]Regression, Logistic
Comparison: Week 9 through Week 24: Odds ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center, age strata and body weight strata.p-value: 0.033595% CI: [1.07, 4.79]Regression, Logistic
Comparison: Week 9 through Week 52: Odds ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center, age strata and body weight strata.p-value: 0.987495% CI: [0.37, 2.65]Regression, Logistic
Comparison: Week 9 through Week 52: Odds ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center, age strata and body weight strata.p-value: 0.018895% CI: [1.19, 6.55]Regression, Logistic
Secondary
Daily Number of Cigarettes Smoked at Baseline
The average number of cigarettes smoked per day in the past 7 days reported at the baseline visit.
Time frame: Baseline
Population: The full analysis set included all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline High Dose | Daily Number of Cigarettes Smoked at Baseline | 10.68 cigarettes smoked per day | Standard Error 0.624 |
| Varenicline Low Dose | Daily Number of Cigarettes Smoked at Baseline | 9.56 cigarettes smoked per day | Standard Error 0.53 |
| Placebo | Daily Number of Cigarettes Smoked at Baseline | 9.57 cigarettes smoked per day | Standard Error 0.531 |
Secondary
Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52
The percentage of participants who reported no smoking and no use of other nicotine-containing products (treatment phase) or tobacco products (non-treatment phase) on the Nicotine Use Inventory in the 7 days prior to the study visits or telephone contacts at Week 12,24 and 52.
Time frame: Weeks 12, 24 and 52
Population: The full analysis set included all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline High Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 24 | 31.2 percentage of participants |
| Varenicline High Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 12 | 31.2 percentage of participants |
| Varenicline High Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 52 | 28.4 percentage of participants |
| Varenicline Low Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 24 | 35.9 percentage of participants |
| Varenicline Low Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 12 | 37.9 percentage of participants |
| Varenicline Low Dose | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 52 | 35.0 percentage of participants |
| Placebo | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 12 | 23.0 percentage of participants |
| Placebo | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 52 | 20.0 percentage of participants |
| Placebo | Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52 | Week 24 | 23.0 percentage of participants |
Comparison: Week 12p-value: 0.579395% CI: [0.62, 2.38]Regression, Logistic
Comparison: Week 12p-value: 0.093295% CI: [0.91, 3.51]Regression, Logistic
Comparison: Week 24p-value: 0.564795% CI: [0.61, 2.5]Regression, Logistic
Comparison: Week 24p-value: 0.291795% CI: [0.72, 2.96]Regression, Logistic
Comparison: Week 52p-value: 0.561695% CI: [0.58, 2.69]Regression, Logistic
Comparison: Week 52p-value: 0.1395% CI: [0.84, 3.78]Regression, Logistic
Other Pre-specified
Change From Baseline in Blood Pressure (BP) at Week 12
Measurement of BP included supine and sitting systolic BP, standing systolic BP, supine and sitting diastolic BP and standing diastolic BP. Blood pressure was taken after participants rested in a sitting position for 5 minutes. BP was recorded after participants had been supine for approximately 5 minutes, and then orthostatic blood pressure was recorded immediately when the participant stood.
Time frame: Baseline, Week 12
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Baseline | 73.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Baseline | 115.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Baseline | 117.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Change at Week 12 | -1.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Baseline | 116.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Baseline | 69.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Baseline | 72.0 millimeters of mercury (mmHg) |
| Varenicline High Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Change at Week 12 | -1.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Baseline | 72.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Baseline | 115.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Baseline | 66.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Change at Week 12 | -1.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Baseline | 70.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Baseline | 114.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Baseline | 115.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Varenicline Low Dose | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Baseline | 113.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Change at Week 12 | 0.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Systolic BP:Change at Week 12 | 2.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Baseline | 112.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Systolic BP:Change at Week 12 | 3.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Baseline | 69.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Baseline | 70.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Standing Diastolic BP:Change at Week 12 | 2.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Diastolic BP:Baseline | 65.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Supine Systolic BP:Baseline | 109.0 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline in Blood Pressure (BP) at Week 12 | Sitting Diastolic BP:Change at Week 12 | 1.0 millimeters of mercury (mmHg) |
Other Pre-specified
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points
The HADS is a self-administered questionnaire measuring anxiety. Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) consisted of 7 items that were assessed on a scale of 0 = no anxiety to 3 = severe feeling of anxiety. Total HADS-A subscale score range from 0 = no anxiety to 21 = severe anxiety; higher scores indicated more severe anxiety.
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 36 | -1.4 units on a scale | Standard Deviation 2.42 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 15 | -1.7 units on a scale | Standard Deviation 2.09 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 8 | -1.5 units on a scale | Standard Deviation 2.11 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 3 | -1.2 units on a scale | Standard Deviation 1.85 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 14 | -1.4 units on a scale | Standard Deviation 2.33 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 9 | -1.4 units on a scale | Standard Deviation 2.17 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 52 | -1.6 units on a scale | Standard Deviation 2.2 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 13 | -1.5 units on a scale | Standard Deviation 2.13 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 10 | -1.4 units on a scale | Standard Deviation 2.07 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 28 | -1.5 units on a scale | Standard Deviation 2.54 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 12 | -1.4 units on a scale | Standard Deviation 2.07 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 11 | -1.4 units on a scale | Standard Deviation 2 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 4 | -1.5 units on a scale | Standard Deviation 1.83 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 44 | -1.8 units on a scale | Standard Deviation 2.21 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 20 | -1.5 units on a scale | Standard Deviation 2.28 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 5 | -1.3 units on a scale | Standard Deviation 2.03 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 2 | -1.1 units on a scale | Standard Deviation 1.95 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Baseline | 2.4 units on a scale | Standard Deviation 2.05 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 6 | -1.5 units on a scale | Standard Deviation 1.91 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 1 | -0.6 units on a scale | Standard Deviation 1.86 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 16 | -1.6 units on a scale | Standard Deviation 2.16 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 7 | -1.6 units on a scale | Standard Deviation 2.13 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 16 | -1.2 units on a scale | Standard Deviation 2.44 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Baseline | 1.9 units on a scale | Standard Deviation 2.06 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 1 | -0.5 units on a scale | Standard Deviation 1.53 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 2 | -0.7 units on a scale | Standard Deviation 1.9 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 3 | -0.8 units on a scale | Standard Deviation 1.96 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 4 | -0.9 units on a scale | Standard Deviation 2.31 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 5 | -1.0 units on a scale | Standard Deviation 2.12 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 6 | -1.0 units on a scale | Standard Deviation 2.25 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 7 | -1.1 units on a scale | Standard Deviation 2.41 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 8 | -1.1 units on a scale | Standard Deviation 2.2 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 9 | -1.2 units on a scale | Standard Deviation 2.35 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 10 | -1.2 units on a scale | Standard Deviation 2.44 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 11 | -1.2 units on a scale | Standard Deviation 2.23 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 12 | -1.3 units on a scale | Standard Deviation 2.31 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 13 | -1.2 units on a scale | Standard Deviation 2.17 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 14 | -1.2 units on a scale | Standard Deviation 2.53 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 15 | -1.3 units on a scale | Standard Deviation 2.43 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 20 | -1.2 units on a scale | Standard Deviation 2.31 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 28 | -1.2 units on a scale | Standard Deviation 2.46 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 36 | -1.2 units on a scale | Standard Deviation 2.51 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 44 | -1.2 units on a scale | Standard Deviation 2.34 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 52 | -1.1 units on a scale | Standard Deviation 2.39 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 14 | -1.2 units on a scale | Standard Deviation 2.19 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 7 | -1.2 units on a scale | Standard Deviation 2.39 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 1 | -0.3 units on a scale | Standard Deviation 1.91 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 15 | -1.0 units on a scale | Standard Deviation 3.35 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 6 | -1.2 units on a scale | Standard Deviation 2.31 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 5 | -1.2 units on a scale | Standard Deviation 2.19 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 16 | -1.1 units on a scale | Standard Deviation 2.54 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 4 | -0.9 units on a scale | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 52 | -1.5 units on a scale | Standard Deviation 2.06 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 20 | -1.3 units on a scale | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 3 | -1.0 units on a scale | Standard Deviation 2.09 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 44 | -1.0 units on a scale | Standard Deviation 1.9 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 28 | -1.2 units on a scale | Standard Deviation 2.38 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 11 | -1.3 units on a scale | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 10 | -1.1 units on a scale | Standard Deviation 2.34 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 2 | -0.5 units on a scale | Standard Deviation 2.18 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 12 | -1.2 units on a scale | Standard Deviation 2.15 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 9 | -1.1 units on a scale | Standard Deviation 2.13 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Baseline | 2.3 units on a scale | Standard Deviation 2.26 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 13 | -1.2 units on a scale | Standard Deviation 2.33 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 8 | -1.3 units on a scale | Standard Deviation 1.99 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points | Change at Week 36 | -1.3 units on a scale | Standard Deviation 2.03 |
Other Pre-specified
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points
Hospital Anxiety and Depression Scale Depression subscale (HADS-D) consists of 7 items that were assessed on a scale of 0 = no depression to 3 = severe feeling of depression. Total HADS-D subscale score range from 0 = no depression to 21 = severe feeling of depression; higher scores indicated a greater intensity of depression.
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 6 | -0.6 units on a scale | Standard Deviation 1.85 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 52 | -0.7 units on a scale | Standard Deviation 1.81 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 16 | -0.6 units on a scale | Standard Deviation 2.09 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 5 | -0.6 units on a scale | Standard Deviation 1.66 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Baseline | 1.5 units on a scale | Standard Deviation 1.93 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 13 | -0.6 units on a scale | Standard Deviation 2.16 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 4 | -0.7 units on a scale | Standard Deviation 1.39 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 1 | -0.4 units on a scale | Standard Deviation 1.43 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 10 | -0.9 units on a scale | Standard Deviation 1.67 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 3 | -0.5 units on a scale | Standard Deviation 1.39 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 2 | -0.5 units on a scale | Standard Deviation 1.57 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 20 | -0.8 units on a scale | Standard Deviation 1.71 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 12 | -0.7 units on a scale | Standard Deviation 1.79 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 9 | -0.8 units on a scale | Standard Deviation 1.63 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 28 | -0.9 units on a scale | Standard Deviation 1.63 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 15 | -0.8 units on a scale | Standard Deviation 1.83 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 8 | -0.8 units on a scale | Standard Deviation 1.87 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 36 | -0.7 units on a scale | Standard Deviation 2.19 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 14 | -0.8 units on a scale | Standard Deviation 1.96 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 7 | -0.7 units on a scale | Standard Deviation 1.52 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 44 | -0.9 units on a scale | Standard Deviation 1.93 |
| Varenicline High Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 11 | -0.7 units on a scale | Standard Deviation 1.53 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 10 | -0.7 units on a scale | Standard Deviation 1.63 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 14 | -0.6 units on a scale | Standard Deviation 1.84 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 15 | -0.8 units on a scale | Standard Deviation 1.84 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 16 | -0.6 units on a scale | Standard Deviation 2.08 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 20 | -0.8 units on a scale | Standard Deviation 1.84 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 28 | -0.8 units on a scale | Standard Deviation 1.9 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 36 | -0.8 units on a scale | Standard Deviation 1.77 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 44 | -0.9 units on a scale | Standard Deviation 1.78 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 52 | -0.8 units on a scale | Standard Deviation 1.67 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Baseline | 1.4 units on a scale | Standard Deviation 1.79 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 1 | -0.2 units on a scale | Standard Deviation 1.18 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 2 | -0.2 units on a scale | Standard Deviation 1.65 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 3 | -0.3 units on a scale | Standard Deviation 1.55 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 4 | -0.3 units on a scale | Standard Deviation 1.79 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 5 | -0.3 units on a scale | Standard Deviation 1.97 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 6 | -0.4 units on a scale | Standard Deviation 1.6 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 7 | -0.5 units on a scale | Standard Deviation 1.91 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 8 | -0.5 units on a scale | Standard Deviation 1.8 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 9 | -0.5 units on a scale | Standard Deviation 1.85 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 13 | -0.7 units on a scale | Standard Deviation 1.79 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 11 | -0.9 units on a scale | Standard Deviation 1.66 |
| Varenicline Low Dose | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 12 | -0.7 units on a scale | Standard Deviation 1.72 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 5 | -0.3 units on a scale | Standard Deviation 1.88 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 44 | -0.3 units on a scale | Standard Deviation 2.44 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 15 | -0.3 units on a scale | Standard Deviation 3.26 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 36 | -0.4 units on a scale | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 12 | -0.6 units on a scale | Standard Deviation 2.11 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 7 | -0.4 units on a scale | Standard Deviation 2.13 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 28 | -0.5 units on a scale | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 11 | -0.5 units on a scale | Standard Deviation 2.11 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 8 | -0.5 units on a scale | Standard Deviation 1.8 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 20 | -0.6 units on a scale | Standard Deviation 2.24 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 14 | -0.5 units on a scale | Standard Deviation 2.22 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 9 | -0.5 units on a scale | Standard Deviation 2.3 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 2 | -0.1 units on a scale | Standard Deviation 1.8 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 1 | 0.1 units on a scale | Standard Deviation 1.61 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 16 | -0.2 units on a scale | Standard Deviation 2.79 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 3 | -0.3 units on a scale | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Baseline | 1.4 units on a scale | Standard Deviation 1.83 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 13 | -0.7 units on a scale | Standard Deviation 1.95 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 4 | -0.4 units on a scale | Standard Deviation 2 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 52 | -0.6 units on a scale | Standard Deviation 2.02 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 6 | -0.5 units on a scale | Standard Deviation 1.83 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points | Change at Week 10 | -0.4 units on a scale | Standard Deviation 2.77 |
Other Pre-specified
Change From Baseline in Pulse Rate at Week 12
Measurement of pulse rate included supine, sitting and standing pulse rate. Pulse rate was taken after participants rested in a sitting position for 5 minutes. Pulse rate was recorded after participants had been supine for approximately 5 minutes and then immediately upon standing.
Time frame: Baseline, Week 12
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Baseline | 75.0 beats per minute (bpm) |
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Change at Week 12 | 0.0 beats per minute (bpm) |
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Baseline | 75.0 beats per minute (bpm) |
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Change at Week 12 | -1.0 beats per minute (bpm) |
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Baseline | 84.0 beats per minute (bpm) |
| Varenicline High Dose | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Change at Week 12 | 1.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Change at Week 12 | -3.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Baseline | 72.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Change at Week 12 | 0.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Baseline | 85.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Change at Week 12 | 1.0 beats per minute (bpm) |
| Varenicline Low Dose | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Baseline | 75.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Change at Week 12 | 3.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Baseline | 77.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Change at Week 12 | -3.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Sitting Pulse Rate:Change at Week 12 | 1.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Supine Pulse Rate:Baseline | 72.0 beats per minute (bpm) |
| Placebo | Change From Baseline in Pulse Rate at Week 12 | Standing Pulse Rate:Baseline | 85.0 beats per minute (bpm) |
Other Pre-specified
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories);was an interview-based instrument to systematically assess suicidal ideation and suicidal behavior.C-SSRS assessed whether participant experienced any of the following:completed suicide;suicide attempt(response of Yes on actual attempt);preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior,aborted attempt or interrupted attempt),suicidal ideation (Yes on wish to be dead,non-specific active suicidal thoughts,active suicidal ideation with methods without intent to act or some intent to act,without specific plan or with specific plan and intent,any self-injurious behavior with no suicidal intent (Yes on Has participant engaged in non-suicidal self-injurious behavior).Here,number of participants with positive response (response of yes) to suicidal behavior or/and Ideation,any non-suicidal self-injurious behavior were reported.
Time frame: Screening, Baseline, Week 1 up to Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (last follow-up [FU])
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Behavior or/and Ideation | 2 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Ideation | 2 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Wish to be Dead | 2 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Non-Specific Active Suicidal Thoughts | 1 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screen:Self Injurious Behavior, no Suicidal Intent | 3 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Behavior or/and Ideation | 1 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Ideation | 1 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Wish to be Dead | 1 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Non-Specific Active Suicidal Thoughts | 0 Participants |
| Varenicline High Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Self Injurious Behavior, no Suicidal Intent | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Non-Specific Active Suicidal Thoughts | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Behavior or/and Ideation | 3 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Behavior or/and Ideation | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screen:Self Injurious Behavior, no Suicidal Intent | 3 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Ideation | 3 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Self Injurious Behavior, no Suicidal Intent | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Wish to be Dead | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Wish to be Dead | 2 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Ideation | 0 Participants |
| Varenicline Low Dose | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Non-Specific Active Suicidal Thoughts | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Wish to be Dead | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Non-Specific Active Suicidal Thoughts | 2 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screen:Self Injurious Behavior, no Suicidal Intent | 2 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Behavior or/and Ideation | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE: Non-Specific Active Suicidal Thoughts | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Suicidal Ideation | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Behavior or/and Ideation | 2 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | TE:Self Injurious Behavior, no Suicidal Intent | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening:Suicidal Ideation | 2 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening: Wish to be Dead | 2 Participants |
Other Pre-specified
Number of Participants With Laboratory Abnormalities
Criteria for laboratory abnormalities: Lymphocytes Absolute (Abs), Lymphocytes percentage (%), Total Neutrophils (Abs), Neutrophils %: \<0.8\*LLN or \>1.2\*ULN; Basophils (Abs), Basophils %Eosinophils (Abs), Eosinophils %, Monocytes (Abs), Monocytes %:\> 1.2\*ULN; Total Bilirubin milligram per deciliter (mg/dl) \>1.5\*ULN; alanine aminotransferase: \>3.0\*ULN; Blood urea nitrogen, Creatinine: \>1.3\*ULN; Uric acid :\> 1.2\*ULN.
Time frame: Baseline up to Week 12
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses. Here, 'Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline High Dose | Number of Participants With Laboratory Abnormalities | 35 Participants |
| Varenicline Low Dose | Number of Participants With Laboratory Abnormalities | 33 Participants |
| Placebo | Number of Participants With Laboratory Abnormalities | 26 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious AEs and SAEs.
Time frame: First dose up to last dose (up-to Week 12) plus 30 days
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline High Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 65 Participants |
| Varenicline Low Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 53 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 52 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE: AE causing: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Solicited AEs collected by semi-structured NAEI inquiring about AEs: depression, anxiety, delusions, hallucinations, paranoia, psychosis, mania, panic, agitation, dissociative states, feeling abnormal, hostility, aggression and homicidal ideation. If a participant had a positive response to any item on the NAEI, investigator determined if it met criteria AE criteria.
Time frame: First dose up to last dose (up-to Week 12) plus 30 days
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varenicline High Dose | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric AEs | 18 Participants |
| Varenicline High Dose | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric SAEs | 0 Participants |
| Varenicline Low Dose | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric AEs | 11 Participants |
| Varenicline Low Dose | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric AEs | 12 Participants |
| Placebo | Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI) | Neuropsychiatric SAEs | 0 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug Varenicline was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious AEs and SAEs.
Time frame: First dose up to last dose (up-to Week 12) plus 30 days
Population: The safety analysis set included all participants who took at least one dose of randomized study medication, including partial doses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline High Dose | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | 46 Participants |
| Varenicline Low Dose | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | 28 Participants |
| Placebo | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | 27 Participants |