Smoking Cessation
Conditions
Keywords
smoking cessation, psychiatric disease
Brief summary
This study is being conducted to assess varenicline and bupropion as aids to smoking cessation treatment in subjects with and without an established diagnosis of major psychiatric disorder and to characterize the neuropsychiatric safety profile (pre-specified adverse events (AEs) in both of these populations).
Interventions
DRUGPlacebo
Triple dummy placebo for each treatment arm
Subjects will be titrated to the full dose during the first week in the following manner: 0.5 mg (tablet form) once a day for 3 days, 0.5 mg twice a day for 4 days, then 1 mg twice a day for 11 weeks
Subjects will receive 150 mg (tablet form) once a day for 3 days and then will take 150 mg twice a day for the remainder of the treatment period (11 weeks and 4 days).
Subjects will start active dosing the morning of the Week 1 visit and will receive a 21 mg transdermal patch per day x 7 weeks, followed by a 14 mg transdermal patch per day x 2 weeks, and then a 7 mg transdermal patch x 2 weeks for a total of 11 weeks of treatment.
Sponsors
GlaxoSmithKline
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female cigarette smokers, 18- 75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt. * Smoked an average of at least 10 cigarettes per day during past year and during the month prior to the screening visit, and exhaled carbon monoxide (CO) \>10 ppm at screening. * For Neuropsychiatric cohort- subjects must have proper diagnosis as outlined in protocol.
Exclusion criteria
* Subjects with a past or current diagnosis of one of the following disorders: a. Psychotic Disorders: * Schizophreniform * Delusional Disorder * Psychotic Disorder NOS b. All Delirium, Dementia, and Amnestic and Other Cognitive Disorders c. All Substance Induced Disorders (Other than nicotine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. |
| Estimated NPS AE Rate (%), by Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Estimated NPS AE rate (%) was calculated based on least-squares means analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The NPS AE composite results (as previously described) are for the two cohorts combined and are presented below. |
| Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint. |
| Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint. |
| Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint. |
| Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The NPS AE endpoint was the occurrence of at least 1 treatment-emergent severe AE of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least 1 treatment-emergent severe AE of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint. |
| Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Baseline to Week 24 | The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms. |
| HADS Total Score, Psychiatric History Cohort | Baseline to Week 24 | The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms. |
| HADS Total Score (Overall) | Baseline to Week 24 | The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms. |
| Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit.The scale is also used to record any completed suicides. |
| Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides. |
| Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Each of these 16 components is reported below. |
| Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Baseline to Week 24 | The CGI-I is a clinician rated instrument that measures change in participant's psychiatric condition (or lack thereof in the stratum without psychiatric disorders) on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse), with 4 = no change. The ratings were applicable even to those without psychiatric diagnoses (eg, those with no psychiatric symptoms would be rated as normal, not at all ill on the CGI-S at baseline and assuming no psychiatric symptoms emerge during the trial, would be rated as no change on the CGI-I at follow-up visits). For those participants with a psychiatric diagnosis, the clinician should rate the severity of the mental illness with respect to the clinician's experience with the psychiatric population to which the participant belongs. |
| CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort | Week 9 through Week 12 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive). |
| CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort | Week 9 through Week 12 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive). |
| CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) | Week 9 through Week 12 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive). |
| CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort | Week 9 through Week 24 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive). |
| CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort | Week 9 through Week 24 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive). |
| CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) | Week 9 through Week 24 | A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive). |
| 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | 24 Weeks | A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days? |
| 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | 24 Weeks | A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days? |
| 7-Day Point Prevalence of Abstinence (Overall) | 24 Weeks | A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days? |
| Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides. |
| Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. | The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Each of these 16 components is reported below. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, Denmark, Finland, Germany, Mexico, New Zealand, Russia, Slovakia, South Africa, Spain, United States
Participant flow
Recruitment details
A total of 11,186 participants were screened for participation in the study, of which 3042 participants were considered to be screen failures, leaving 8144 participants eligible for study participation (efficacy population). 86 participants (1.1%) did not receive study drug. A total of 8058 participants received study drug (safety population).
Pre-assignment details
Participants were classified into 2 cohorts: participants without diagnosis of psychiatric disorder and participants with a stable diagnosis of psychiatric disorder confirmed by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) 4th edition conducted at screening.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 1.0 mg BID Participants were randomized to 1 of the 3 active dosing groups that took active medication of either varenicline, bupropion, NRT in this triple-dummy design. Participants in this arm received varenicline titrated to the full dose during the first week in the following manner: 0.5 mg QD x 3 days, 0.5 mg BID x 4 days, then 1 mg BID for 11 weeks. They also received placebo bupropion and NRT patch, dosed in the same manner as the active medication. | 2,016 |
| Bupropion Participants were randomized to 1 of the 3 active dosing groups that took active medication of either varenicline, bupropion, NRT in this triple-dummy design. Participants in this arm received bupropion 150 mg QD x 3 days and taken 150 mg BID for the remainder of the treatment period (11 weeks and 4 days). They also received placebo varenicline and NRT patch, dosed in the same manner as the active medication. | 2,006 |
| NRT Patch Participants were randomized to 1 of the 3 active dosing groups that took active medication of either varenicline, bupropion, NRT in this triple-dummy design. Participants in this arm received NRT started active dosing the morning of the Week 1 visit and received a 21 mg transdermal patch per day x 7 weeks, followed by a 14 mg transdermal patch per day x 2 weeks, and then a 7 mg transdermal patch x 2 weeks for a total of 11 weeks of treatment. They also received placebo varenicline and bupropion, dosed in the same manner as active medication. | 2,022 |
| Placebo Participants received matching placebo for varenicline, bupropion, and NRT in this triple-dummy design, and followed the same titration and dosing schedule as for the active treatments noted above. | 2,014 |
| Total | 8,058 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse event (study drug) | 25 | 21 | 26 | 17 |
| Overall Study | Adverse event (study drug unrelated) | 9 | 7 | 9 | 9 |
| Overall Study | Death | 0 | 3 | 1 | 3 |
| Overall Study | Insufficient clinical response | 4 | 4 | 14 | 13 |
| Overall Study | Lost to Follow-up | 135 | 126 | 144 | 127 |
| Overall Study | Medication error | 0 | 1 | 0 | 1 |
| Overall Study | No longer meets eligibility criteria | 4 | 8 | 6 | 5 |
| Overall Study | No longer willing to participate | 195 | 218 | 224 | 248 |
| Overall Study | Other reason | 41 | 30 | 36 | 33 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 4 | 2 | 5 | 5 |
| Overall Study | Randomized but not treated | 21 | 28 | 16 | 21 |
Baseline characteristics
| Characteristic | Varenicline 1.0 mg BID | Bupropion | NRT Patch | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.5 Years STANDARD_DEVIATION 12.4 | 46.3 Years STANDARD_DEVIATION 12.6 | 46.8 Years STANDARD_DEVIATION 12.2 | 46.4 Years STANDARD_DEVIATION 12.2 | 46.5 Years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 1114 Participants | 1116 Participants | 1141 Participants | 1138 Participants | 4509 Participants |
| Sex: Female, Male Male | 902 Participants | 890 Participants | 881 Participants | 876 Participants | 3549 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1,158 / 2,016 | 1,033 / 2,006 | 1,003 / 2,022 | 884 / 2,014 |
| serious Total, serious adverse events | 39 / 2,016 | 48 / 2,006 | 45 / 2,022 | 41 / 2,014 |
Outcome results
Primary
Estimated NPS AE Rate (%), by Cohort
The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Estimated NPS AE rate (%) was calculated based on least-squares means analysis.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Estimated NPS AE Rate (%), by Cohort | Psychiatric cohort (N= 4074) | 6.42 percentage of participants |
| Varenicline 1.0 mg BID | Estimated NPS AE Rate (%), by Cohort | Non-psychiatric cohort (N=3984) | 1.25 percentage of participants |
| Bupropion 150 mg BID | Estimated NPS AE Rate (%), by Cohort | Psychiatric cohort (N= 4074) | 6.62 percentage of participants |
| Bupropion 150 mg BID | Estimated NPS AE Rate (%), by Cohort | Non-psychiatric cohort (N=3984) | 2.44 percentage of participants |
| NRT Patch | Estimated NPS AE Rate (%), by Cohort | Non-psychiatric cohort (N=3984) | 2.31 percentage of participants |
| NRT Patch | Estimated NPS AE Rate (%), by Cohort | Psychiatric cohort (N= 4074) | 5.20 percentage of participants |
| Placebo | Estimated NPS AE Rate (%), by Cohort | Psychiatric cohort (N= 4074) | 4.83 percentage of participants |
| Placebo | Estimated NPS AE Rate (%), by Cohort | Non-psychiatric cohort (N=3984) | 2.52 percentage of participants |
Comparison: Non-psychiatric cohort95% CI: [-2.4, -0.15]Regression, Linear
Comparison: Non-psychiatric cohort95% CI: [-1.37, 1.21]Regression, Linear
Comparison: Non-psychiatric cohort95% CI: [-1.54, 1.12]Regression, Linear
Comparison: Psychiatric cohort95% CI: [-0.42, 3.59]Regression, Linear
Comparison: Psychiatric cohort95% CI: [-0.24, 3.81]Regression, Linear
Comparison: Psychiatric cohort95% CI: [-1.53, 2.26]Regression, Linear
Primary
Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint
The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 1.3 percentage of participants |
| Varenicline 1.0 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 6.5 percentage of participants |
| Varenicline 1.0 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Overall (N= 2016, 2006, 2022, 2014) | 4.0 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 2.2 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 6.7 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Overall (N= 2016, 2006, 2022, 2014) | 4.5 percentage of participants |
| NRT Patch | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Overall (N= 2016, 2006, 2022, 2014) | 3.9 percentage of participants |
| NRT Patch | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 5.2 percentage of participants |
| NRT Patch | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 2.5 percentage of participants |
| Placebo | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 4.9 percentage of participants |
| Placebo | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 2.4 percentage of participants |
| Placebo | Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint | Overall (N= 2016, 2006, 2022, 2014) | 3.7 percentage of participants |
Comparison: The reduced (final) statistical model included treatment group, cohort and region, plus the 2-way interaction of treatment by cohort. Other interactions not included due to lack of significance. Region reduced to 2-level to address event sparseness issue.p-value: 0.0652Regression, Linear
Secondary
7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?
Time frame: 24 Weeks
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 4 | 34.3 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 20 | 35.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 12 | 44.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 11 | 46.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 5 | 38.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 18 | 40.9 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 10 | 42.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 9 | 47.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 6 | 41.0 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 8 | 42.3 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 7 | 44.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 3 | 30.0 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 24 | 33.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 22 | 38.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 19 | 39.9 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 17 | 40.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 21 | 38.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 16 | 37.2 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 15 | 43.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 1 | 1.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 2 | 20.9 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 23 | 37.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 14 | 44.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 13 | 41.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 16 | 28.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 3 | 26.6 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 7 | 35.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 8 | 31.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 1 | 1.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 18 | 31.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 24 | 26.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 2 | 21.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 4 | 27.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 5 | 29.8 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 6 | 31.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 9 | 34.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 10 | 31.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 11 | 34.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 12 | 30.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 13 | 30.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 14 | 33.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 15 | 33.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 17 | 31.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 19 | 31.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 20 | 27.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 21 | 30.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 22 | 29.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 23 | 30.6 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 2 | 15.5 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 1 | 1.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 18 | 31.7 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 14 | 32.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 4 | 25.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 19 | 31.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 11 | 34.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 7 | 35.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 23 | 28.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 20 | 26.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 22 | 29.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 15 | 32.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 6 | 30.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 8 | 31.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 3 | 22.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 24 | 27.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 16 | 28.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 9 | 34.8 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 13 | 29.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 5 | 27.8 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 12 | 30.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 10 | 31.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 17 | 31.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 21 | 29.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 4 | 14.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 11 | 20.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 21 | 20.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 12 | 17.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 2 | 11.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 13 | 17.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 14 | 20.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 16 | 18.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 15 | 21.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 22 | 20.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 1 | 1.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 17 | 20.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 7 | 19.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 18 | 20.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 24 | 17.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 19 | 20.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 20 | 18.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 6 | 15.9 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 8 | 16.7 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 5 | 14.9 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 3 | 13.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 9 | 19.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 23 | 20.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort | Week 10 | 16.9 percentage of participants |
Secondary
7-Day Point Prevalence of Abstinence (Overall)
A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?
Time frame: 24 Weeks
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 10 | 38.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 8 | 37.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 23 | 33.0 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 21 | 33.9 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 6 | 35.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 16 | 33.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 14 | 39.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 22 | 33.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 7 | 39.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 9 | 41.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 19 | 35.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 24 | 29.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 12 | 39.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 2 | 18.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 1 | 1.3 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 5 | 33.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 18 | 36.2 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 15 | 38.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 11 | 42.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 13 | 36.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 3 | 26.3 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 20 | 30.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 17 | 36.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 4 | 30.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 12 | 27.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 4 | 24.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 18 | 27.8 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 5 | 25.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 17 | 27.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 11 | 30.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 6 | 26.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 10 | 27.6 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 23 | 27.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 9 | 30.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 16 | 25.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 15 | 29.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 19 | 27.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 20 | 23.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 7 | 30.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 14 | 29.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 21 | 26.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 8 | 26.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 22 | 26.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 13 | 26.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 24 | 23.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 1 | 1.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 2 | 17.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence (Overall) | Week 3 | 22.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 18 | 28.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 9 | 32.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 23 | 25.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 19 | 28.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 20 | 23.7 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 21 | 26.5 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 22 | 26.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 24 | 23.6 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 1 | 0.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 2 | 14.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 3 | 20.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 4 | 23.5 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 5 | 25.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 6 | 26.8 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 7 | 31.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 8 | 28.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 10 | 28.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 11 | 32.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 12 | 27.6 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 13 | 26.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 14 | 29.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 15 | 29.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 16 | 24.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence (Overall) | Week 17 | 28.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 4 | 13.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 3 | 12.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 17 | 18.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 12 | 16.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 2 | 10.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 22 | 18.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 16 | 16.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 13 | 16.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 21 | 18.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 20 | 16.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 1 | 1.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 14 | 19.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 19 | 19.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 18 | 19.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 10 | 15.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 15 | 19.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 8 | 15.9 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 9 | 18.1 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 7 | 17.9 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 6 | 14.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 24 | 15.7 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 5 | 13.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 23 | 18.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence (Overall) | Week 11 | 18.8 percentage of participants |
Secondary
7-Day Point Prevalence of Abstinence, Psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 3 and 6 on the nicotine use inventory at that specific visit. NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?
Time frame: 24 Weeks
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 13 | 32.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 2 | 16.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 11 | 38.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 7 | 34.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 6 | 30.8 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 3 | 22.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 12 | 35.0 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 5 | 28.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 24 | 26.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 22 | 29.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 15 | 33.4 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 21 | 29.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 20 | 26.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 19 | 31.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 23 | 28.5 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 4 | 26.6 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 10 | 35.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 16 | 29.1 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 14 | 34.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 9 | 36.2 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 8 | 32.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 17 | 32.3 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 18 | 31.7 percentage of participants |
| Varenicline 1.0 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 1 | 1.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 15 | 25.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 6 | 22.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 8 | 22.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 17 | 24.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 16 | 21.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 1 | 1.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 2 | 14.6 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 3 | 18.1 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 4 | 21.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 5 | 21.8 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 7 | 25.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 9 | 26.0 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 10 | 24.3 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 18 | 24.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 19 | 24.7 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 20 | 20.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 21 | 23.2 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 22 | 22.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 23 | 23.5 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 24 | 20.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 11 | 27.4 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 12 | 23.9 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 13 | 22.6 percentage of participants |
| Bupropion 150 mg BID | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 14 | 25.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 13 | 24.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 22 | 23.6 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 4 | 21.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 23 | 22.2 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 10 | 25.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 19 | 25.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 9 | 29.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 24 | 20.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 12 | 24.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 8 | 24.6 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 20 | 25.1 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 3 | 17.9 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 18 | 24.7 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 5 | 22.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 17 | 24.8 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 1 | 0.7 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 6 | 23.3 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 21 | 23.7 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 2 | 13.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 14 | 26.8 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 7 | 27.5 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 11 | 29.4 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 15 | 26.0 percentage of participants |
| NRT Patch | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 16 | 21.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 8 | 15.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 9 | 17.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 15 | 18.3 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 14 | 17.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 10 | 14.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 18 | 18.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 12 | 14.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 19 | 17.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 17 | 17.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 20 | 17.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 21 | 17.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 22 | 16.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 23 | 16.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 13 | 14.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 1 | 0.5 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 3 | 10.7 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 24 | 14.0 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 4 | 11.8 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 11 | 17.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 5 | 12.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 2 | 9.2 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 6 | 13.4 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 7 | 16.6 percentage of participants |
| Placebo | 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort | Week 16 | 13.9 percentage of participants |
Secondary
Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit
The CGI-I is a clinician rated instrument that measures change in participant's psychiatric condition (or lack thereof in the stratum without psychiatric disorders) on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse), with 4 = no change. The ratings were applicable even to those without psychiatric diagnoses (eg, those with no psychiatric symptoms would be rated as normal, not at all ill on the CGI-S at baseline and assuming no psychiatric symptoms emerge during the trial, would be rated as no change on the CGI-I at follow-up visits). For those participants with a psychiatric diagnosis, the clinician should rate the severity of the mental illness with respect to the clinician's experience with the psychiatric population to which the participant belongs.
Time frame: Baseline to Week 24
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 24 (N= 1533, 1515, 1499, 1497) | 71.8 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 20 (N= 1563, 1573, 1523, 1510) | 73.4 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 8 (N= 1758, 1756, 1755, 1738) | 82.4 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 6 (N= 1816, 1808, 1820, 1773) | 85.2 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 16 (N= 1586, 1606, 1568, 1541) | 74.2 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 1 (N= 1986, 1974, 1986, 1982) | 94.2 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 12 (N= 1558, 1572, 1540, 1492) | 72.9 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 10 (N= 1717, 1707, 1715, 1675) | 80.6 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 13 (N= 1612, 16081602, 1575) | 75.9 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 2 (N= 1934, 1936, 1927, 1926) | 90.8 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 4 (N= 1860, 1856, 1858, 1834) | 86.6 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 5 (N= 1828, 1816, 1822, 1802) | 85.7 percentage of participants |
| Varenicline 1.0 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 3 (N= 1880, 1892, 1880, 1863) | 88.3 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 10 (N= 1717, 1707, 1715, 1675) | 81.7 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 3 (N= 1880, 1892, 1880, 1863) | 89.8 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 5 (N= 1828, 1816, 1822, 1802) | 86.5 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 12 (N= 1558, 1572, 1540, 1492) | 75.1 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 13 (N= 1612, 16081602, 1575) | 76.7 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 4 (N= 1860, 1856, 1858, 1834) | 88.0 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 16 (N= 1586, 1606, 1568, 1541) | 76.7 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 6 (N= 1816, 1808, 1820, 1773) | 86.5 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 20 (N= 1563, 1573, 1523, 1510) | 75.0 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 1 (N= 1986, 1974, 1986, 1982) | 93.2 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 8 (N= 1758, 1756, 1755, 1738) | 83.6 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 2 (N= 1934, 1936, 1927, 1926) | 90.8 percentage of participants |
| Bupropion 150 mg BID | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 24 (N= 1533, 1515, 1499, 1497) | 72.3 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 24 (N= 1533, 1515, 1499, 1497) | 71.1 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 8 (N= 1758, 1756, 1755, 1738) | 82.8 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 12 (N= 1558, 1572, 1540, 1492) | 72.2 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 13 (N= 1612, 16081602, 1575) | 75.2 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 16 (N= 1586, 1606, 1568, 1541) | 73.9 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 1 (N= 1986, 1974, 1986, 1982) | 94.6 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 2 (N= 1934, 1936, 1927, 1926) | 90.5 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 4 (N= 1860, 1856, 1858, 1834) | 87.1 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 5 (N= 1828, 1816, 1822, 1802) | 85.5 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 6 (N= 1816, 1808, 1820, 1773) | 85.1 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 10 (N= 1717, 1707, 1715, 1675) | 80.4 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 20 (N= 1563, 1573, 1523, 1510) | 72.2 percentage of participants |
| NRT Patch | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 3 (N= 1880, 1892, 1880, 1863) | 88.7 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 2 (N= 1934, 1936, 1927, 1926) | 91.2 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 8 (N= 1758, 1756, 1755, 1738) | 81.9 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 12 (N= 1558, 1572, 1540, 1492) | 71.3 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 1 (N= 1986, 1974, 1986, 1982) | 95.1 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 24 (N= 1533, 1515, 1499, 1497) | 71.1 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 13 (N= 1612, 16081602, 1575) | 74.9 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 16 (N= 1586, 1606, 1568, 1541) | 73.4 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 10 (N= 1717, 1707, 1715, 1675) | 79.2 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 3 (N= 1880, 1892, 1880, 1863) | 87.9 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 20 (N= 1563, 1573, 1523, 1510) | 71.7 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 6 (N= 1816, 1808, 1820, 1773) | 84.1 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 5 (N= 1828, 1816, 1822, 1802) | 85.4 percentage of participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), No Change Rating by Visit | Week 4 (N= 1860, 1856, 1858, 1834) | 86.3 percentage of participants |
Secondary
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
Time frame: Week 9 through Week 12
Population: The full analysis set was defined under the intent-to-treat (ITT) principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort | 38.0 percentage of participants |
| Bupropion 150 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort | 26.1 percentage of participants |
| NRT Patch | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort | 26.4 percentage of participants |
| Placebo | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort | 13.7 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [3.2, 5]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.8, 2.85]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.83, 2.9]Regression, Logistic
Secondary
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall)
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
Time frame: Week 9 through Week 12
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) | 33.5 percentage of participants |
| Bupropion 150 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) | 22.6 percentage of participants |
| NRT Patch | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) | 23.4 percentage of participants |
| Placebo | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) | 12.5 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [3.07, 4.24]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.75, 2.45]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.82, 2.54]Regression, Logistic
Secondary
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
Time frame: Week 9 through Week 12
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort | 29.2 percentage of participants |
| Bupropion 150 mg BID | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort | 19.3 percentage of participants |
| NRT Patch | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort | 20.4 percentage of participants |
| Placebo | CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort | 11.4 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [2.56, 4.11]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.46, 2.39]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.56, 2.55]Regression, Logistic
Secondary
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
Time frame: Week 9 through Week 24
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort | 25.5 percentage of participants |
| Bupropion 150 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort | 18.8 percentage of participants |
| NRT Patch | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort | 18.5 percentage of participants |
| Placebo | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort | 10.5 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [2.33, 3.83]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.54, 2.59]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.51, 2.54]Regression, Logistic
Secondary
CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall)
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
Time frame: Week 9 through Week 24
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) | 21.8 percentage of participants |
| Bupropion 150 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) | 16.2 percentage of participants |
| NRT Patch | CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) | 15.7 percentage of participants |
| Placebo | CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) | 9.4 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [2.28, 3.3]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.56, 2.29]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment and region. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.49, 2.19]Regression, Logistic
Secondary
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort
A responder to this endpoint requires the answer no to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
Time frame: Week 9 through Week 24
Population: The full analysis set was defined under the ITT principle as all randomized participants (N=8144) and was used for all efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline 1.0 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort | 18.3 percentage of participants |
| Bupropion 150 mg BID | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort | 13.7 percentage of participants |
| NRT Patch | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort | 13.0 percentage of participants |
| Placebo | CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort | 8.3 percentage of participants |
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.9, 3.29]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.33, 2.36]Regression, Logistic
Comparison: The analysis was done using a logistic regression with terms treatment, cohort, region, treatment by cohort interaction, and region by cohort interaction. Region reduced to 2-level for consistency with primary safety model.p-value: <0.000195% CI: [1.24, 2.2]Regression, Logistic
Secondary
HADS Total Score (Overall)
The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
Time frame: Baseline to Week 24
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 20 (N= 1555, 1569, 1525, 1509) | 3.65 Units on a scale | Standard Deviation 5.18 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 6 (N= 1816, 1807, 1821, 1771) | 3.82 Units on a scale | Standard Deviation 5.27 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 8 (N= 1755, 1754, 1755, 1736) | 3.82 Units on a scale | Standard Deviation 5.36 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 24 (N= 1528, 1512, 1495, 1487) | 3.62 Units on a scale | Standard Deviation 5.33 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 12 (N= 1562, 1571, 1548, 1491) | 3.64 Units on a scale | Standard Deviation 5.21 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 1 (N= 1989, 1976, 1985, 1987) | 5.03 Units on a scale | Standard Deviation 5.45 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 16 (N= 1579, 1602, 1566, 1537) | 3.67 Units on a scale | Standard Deviation 5.37 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 2 (N= 1938, 1937, 1931, 1929) | 4.68 Units on a scale | Standard Deviation 5.55 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 10 (N= 1717, 1709, 1716, 1669) | 3.85 Units on a scale | Standard Deviation 5.49 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 4 (N= 1858, 1854, 1863, 1831) | 4.15 Units on a scale | Standard Deviation 5.5 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 3 (N= 1882, 1891, 1881, 1867) | 4.31 Units on a scale | Standard Deviation 5.44 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 13 (N= 1610, 1608, 1603, 1570) | 3.60 Units on a scale | Standard Deviation 5.29 |
| Varenicline 1.0 mg BID | HADS Total Score (Overall) | Week 5 (N= 1829, 1815, 1820, 1797) | 3.94 Units on a scale | Standard Deviation 5.37 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 13 (N= 1610, 1608, 1603, 1570) | 3.66 Units on a scale | Standard Deviation 5.47 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 12 (N= 1562, 1571, 1548, 1491) | 3.79 Units on a scale | Standard Deviation 5.58 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 5 (N= 1829, 1815, 1820, 1797) | 4.16 Units on a scale | Standard Deviation 5.52 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 6 (N= 1816, 1807, 1821, 1771) | 4.05 Units on a scale | Standard Deviation 5.52 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 2 (N= 1938, 1937, 1931, 1929) | 5.06 Units on a scale | Standard Deviation 5.73 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 8 (N= 1755, 1754, 1755, 1736) | 4.10 Units on a scale | Standard Deviation 5.75 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 20 (N= 1555, 1569, 1525, 1509) | 3.73 Units on a scale | Standard Deviation 5.44 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 10 (N= 1717, 1709, 1716, 1669) | 3.86 Units on a scale | Standard Deviation 5.48 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 16 (N= 1579, 1602, 1566, 1537) | 3.77 Units on a scale | Standard Deviation 5.63 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 3 (N= 1882, 1891, 1881, 1867) | 4.60 Units on a scale | Standard Deviation 5.63 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 4 (N= 1858, 1854, 1863, 1831) | 4.39 Units on a scale | Standard Deviation 5.65 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 1 (N= 1989, 1976, 1985, 1987) | 5.61 Units on a scale | Standard Deviation 6.07 |
| Bupropion 150 mg BID | HADS Total Score (Overall) | Week 24 (N= 1528, 1512, 1495, 1487) | 3.80 Units on a scale | Standard Deviation 5.64 |
| NRT Patch | HADS Total Score (Overall) | Week 24 (N= 1528, 1512, 1495, 1487) | 3.82 Units on a scale | Standard Deviation 5.41 |
| NRT Patch | HADS Total Score (Overall) | Week 6 (N= 1816, 1807, 1821, 1771) | 4.01 Units on a scale | Standard Deviation 5.42 |
| NRT Patch | HADS Total Score (Overall) | Week 20 (N= 1555, 1569, 1525, 1509) | 3.72 Units on a scale | Standard Deviation 5.33 |
| NRT Patch | HADS Total Score (Overall) | Week 1 (N= 1989, 1976, 1985, 1987) | 4.95 Units on a scale | Standard Deviation 5.58 |
| NRT Patch | HADS Total Score (Overall) | Week 2 (N= 1938, 1937, 1931, 1929) | 4.74 Units on a scale | Standard Deviation 5.7 |
| NRT Patch | HADS Total Score (Overall) | Week 3 (N= 1882, 1891, 1881, 1867) | 4.48 Units on a scale | Standard Deviation 5.71 |
| NRT Patch | HADS Total Score (Overall) | Week 4 (N= 1858, 1854, 1863, 1831) | 4.31 Units on a scale | Standard Deviation 5.64 |
| NRT Patch | HADS Total Score (Overall) | Week 5 (N= 1829, 1815, 1820, 1797) | 4.08 Units on a scale | Standard Deviation 5.59 |
| NRT Patch | HADS Total Score (Overall) | Week 8 (N= 1755, 1754, 1755, 1736) | 3.96 Units on a scale | Standard Deviation 5.43 |
| NRT Patch | HADS Total Score (Overall) | Week 10 (N= 1717, 1709, 1716, 1669) | 4.00 Units on a scale | Standard Deviation 5.47 |
| NRT Patch | HADS Total Score (Overall) | Week 12 (N= 1562, 1571, 1548, 1491) | 3.78 Units on a scale | Standard Deviation 5.42 |
| NRT Patch | HADS Total Score (Overall) | Week 13 (N= 1610, 1608, 1603, 1570) | 3.71 Units on a scale | Standard Deviation 5.32 |
| NRT Patch | HADS Total Score (Overall) | Week 16 (N= 1579, 1602, 1566, 1537) | 3.78 Units on a scale | Standard Deviation 5.44 |
| Placebo | HADS Total Score (Overall) | Week 12 (N= 1562, 1571, 1548, 1491) | 3.95 Units on a scale | Standard Deviation 5.42 |
| Placebo | HADS Total Score (Overall) | Week 4 (N= 1858, 1854, 1863, 1831) | 4.39 Units on a scale | Standard Deviation 5.6 |
| Placebo | HADS Total Score (Overall) | Week 3 (N= 1882, 1891, 1881, 1867) | 4.38 Units on a scale | Standard Deviation 5.37 |
| Placebo | HADS Total Score (Overall) | Week 6 (N= 1816, 1807, 1821, 1771) | 4.09 Units on a scale | Standard Deviation 5.48 |
| Placebo | HADS Total Score (Overall) | Week 13 (N= 1610, 1608, 1603, 1570) | 3.70 Units on a scale | Standard Deviation 5.34 |
| Placebo | HADS Total Score (Overall) | Week 1 (N= 1989, 1976, 1985, 1987) | 5.05 Units on a scale | Standard Deviation 5.41 |
| Placebo | HADS Total Score (Overall) | Week 24 (N= 1528, 1512, 1495, 1487) | 3.62 Units on a scale | Standard Deviation 5.27 |
| Placebo | HADS Total Score (Overall) | Week 2 (N= 1938, 1937, 1931, 1929) | 4.80 Units on a scale | Standard Deviation 5.53 |
| Placebo | HADS Total Score (Overall) | Week 16 (N= 1579, 1602, 1566, 1537) | 3.82 Units on a scale | Standard Deviation 5.5 |
| Placebo | HADS Total Score (Overall) | Week 20 (N= 1555, 1569, 1525, 1509) | 3.75 Units on a scale | Standard Deviation 5.47 |
| Placebo | HADS Total Score (Overall) | Week 10 (N= 1717, 1709, 1716, 1669) | 4.04 Units on a scale | Standard Deviation 5.67 |
| Placebo | HADS Total Score (Overall) | Week 5 (N= 1829, 1815, 1820, 1797) | 4.14 Units on a scale | Standard Deviation 5.51 |
| Placebo | HADS Total Score (Overall) | Week 8 (N= 1755, 1754, 1755, 1736) | 4.12 Units on a scale | Standard Deviation 5.56 |
Secondary
HADS Total Score, Psychiatric History Cohort
The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
Time frame: Baseline to Week 24
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 12 (N= 790, 803, 798, 749) | 5.17 Units on a scale | Standard Deviation 6.09 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 6 (N= 917, 914, 912, 874) | 5.39 Units on a scale | Standard Deviation 6.14 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 24 (N= 770, 764, 758, 729) | 5.21 Units on a scale | Standard Deviation 6.27 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 8 (N= 887, 893, 878, 859) | 5.43 Units on a scale | Standard Deviation 6.24 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 16 (N= 795, 805, 791, 748) | 5.26 Units on a scale | Standard Deviation 6.35 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 10 (N= 864, 865, 864, 823) | 5.38 Units on a scale | Standard Deviation 6.35 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 1 (N= 1026, 1017, 1015, 1015) | 6.76 Units on a scale | Standard Deviation 6.14 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 2 (N= 1005, 1004, 996, 995) | 6.42 Units on a scale | Standard Deviation 6.36 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 20 (N= 784, 784, 763, 737) | 5.17 Units on a scale | Standard Deviation 6.02 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 3 (N= 947, 961, 945, 926) | 5.99 Units on a scale | Standard Deviation 6.21 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 13 (N= 813, 812, 814, 763) | 5.06 Units on a scale | Standard Deviation 6.11 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 4 (N= 935, 938, 929, 908) | 5.87 Units on a scale | Standard Deviation 6.39 |
| Varenicline 1.0 mg BID | HADS Total Score, Psychiatric History Cohort | Week 5 (N= 918, 918, 914, 895) | 5.58 Units on a scale | Standard Deviation 6.32 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 16 (N= 795, 805, 791, 748) | 5.62 Units on a scale | Standard Deviation 6.68 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 2 (N= 1005, 1004, 996, 995) | 6.99 Units on a scale | Standard Deviation 6.47 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 6 (N= 917, 914, 912, 874) | 5.87 Units on a scale | Standard Deviation 6.41 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 24 (N= 770, 764, 758, 729) | 5.69 Units on a scale | Standard Deviation 6.64 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 10 (N= 864, 865, 864, 823) | 5.72 Units on a scale | Standard Deviation 6.5 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 13 (N= 813, 812, 814, 763) | 5.44 Units on a scale | Standard Deviation 6.54 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 8 (N= 887, 893, 878, 859) | 5.96 Units on a scale | Standard Deviation 6.68 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 4 (N= 935, 938, 929, 908) | 6.36 Units on a scale | Standard Deviation 6.55 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 3 (N= 947, 961, 945, 926) | 6.51 Units on a scale | Standard Deviation 6.39 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 12 (N= 790, 803, 798, 749) | 5.66 Units on a scale | Standard Deviation 6.63 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 1 (N= 1026, 1017, 1015, 1015) | 7.58 Units on a scale | Standard Deviation 6.87 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 5 (N= 918, 918, 914, 895) | 6.03 Units on a scale | Standard Deviation 6.41 |
| Bupropion 150 mg BID | HADS Total Score, Psychiatric History Cohort | Week 20 (N= 784, 784, 763, 737) | 5.54 Units on a scale | Standard Deviation 6.44 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 4 (N= 935, 938, 929, 908) | 6.16 Units on a scale | Standard Deviation 6.51 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 10 (N= 864, 865, 864, 823) | 5.64 Units on a scale | Standard Deviation 6.3 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 12 (N= 790, 803, 798, 749) | 5.44 Units on a scale | Standard Deviation 6.3 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 1 (N= 1026, 1017, 1015, 1015) | 6.82 Units on a scale | Standard Deviation 6.33 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 2 (N= 1005, 1004, 996, 995) | 6.64 Units on a scale | Standard Deviation 6.55 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 3 (N= 947, 961, 945, 926) | 6.30 Units on a scale | Standard Deviation 6.55 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 5 (N= 918, 918, 914, 895) | 5.82 Units on a scale | Standard Deviation 6.44 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 6 (N= 917, 914, 912, 874) | 5.62 Units on a scale | Standard Deviation 6.22 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 8 (N= 887, 893, 878, 859) | 5.63 Units on a scale | Standard Deviation 6.36 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 13 (N= 813, 812, 814, 763) | 5.36 Units on a scale | Standard Deviation 6.2 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 16 (N= 795, 805, 791, 748) | 5.44 Units on a scale | Standard Deviation 6.34 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 20 (N= 784, 784, 763, 737) | 5.46 Units on a scale | Standard Deviation 6.18 |
| NRT Patch | HADS Total Score, Psychiatric History Cohort | Week 24 (N= 770, 764, 758, 729) | 5.57 Units on a scale | Standard Deviation 6.32 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 4 (N= 935, 938, 929, 908) | 6.04 Units on a scale | Standard Deviation 6.31 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 13 (N= 813, 812, 814, 763) | 5.09 Units on a scale | Standard Deviation 5.96 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 3 (N= 947, 961, 945, 926) | 6.02 Units on a scale | Standard Deviation 6.1 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 12 (N= 790, 803, 798, 749) | 5.42 Units on a scale | Standard Deviation 6.13 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 16 (N= 795, 805, 791, 748) | 5.37 Units on a scale | Standard Deviation 6.38 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 2 (N= 1005, 1004, 996, 995) | 6.42 Units on a scale | Standard Deviation 6.17 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 1 (N= 1026, 1017, 1015, 1015) | 6.70 Units on a scale | Standard Deviation 5.94 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 24 (N= 770, 764, 758, 729) | 5.04 Units on a scale | Standard Deviation 5.97 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 20 (N= 784, 784, 763, 737) | 5.26 Units on a scale | Standard Deviation 6.22 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 8 (N= 887, 893, 878, 859) | 5.63 Units on a scale | Standard Deviation 6.26 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 6 (N= 917, 914, 912, 874) | 5.75 Units on a scale | Standard Deviation 6.26 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 10 (N= 864, 865, 864, 823) | 5.55 Units on a scale | Standard Deviation 6.38 |
| Placebo | HADS Total Score, Psychiatric History Cohort | Week 5 (N= 918, 918, 914, 895) | 5.80 Units on a scale | Standard Deviation 6.31 |
Secondary
Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort
The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
Time frame: Baseline to Week 24
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 13 (N= 797, 796, 789, 807) | 2.11 Units on a scale | Standard Deviation 3.74 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 8 (N= 868, 861, 877, 877) | 2.17 Units on a scale | Standard Deviation 3.6 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 10 (N= 853, 844, 852, 846) | 2.29 Units on a scale | Standard Deviation 3.89 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 1 (N= 984, 972, 989, 992) | 3.26 Units on a scale | Standard Deviation 3.92 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 12 (N= 772, 768, 750, 742) | 2.07 Units on a scale | Standard Deviation 3.48 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 4 (N= 923, 916, 934, 923) | 2.40 Units on a scale | Standard Deviation 3.66 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 20 (N= 771, 785, 762, 772) | 2.10 Units on a scale | Standard Deviation 3.54 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 2 (N= 961, 954, 963, 970) | 2.91 Units on a scale | Standard Deviation 3.86 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 3 (N= 935, 930, 936, 941) | 2.61 Units on a scale | Standard Deviation 3.85 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 6 (N= 899, 893, 909, 897) | 2.23 Units on a scale | Standard Deviation 3.56 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 16 (N= 784, 797, 775, 789) | 2.05 Units on a scale | Standard Deviation 3.47 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 5 (N= 911, 897, 906, 902) | 2.29 Units on a scale | Standard Deviation 3.51 |
| Varenicline 1.0 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 24 (N= 758, 748, 737, 758) | 2.01 Units on a scale | Standard Deviation 3.49 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 2 (N= 961, 954, 963, 970) | 3.07 Units on a scale | Standard Deviation 3.96 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 4 (N= 923, 916, 934, 923) | 2.36 Units on a scale | Standard Deviation 3.57 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 8 (N= 868, 861, 877, 877) | 2.16 Units on a scale | Standard Deviation 3.7 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 20 (N= 771, 785, 762, 772) | 1.93 Units on a scale | Standard Deviation 3.36 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 12 (N= 772, 768, 750, 742) | 1.83 Units on a scale | Standard Deviation 3.21 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 6 (N= 899, 893, 909, 897) | 2.18 Units on a scale | Standard Deviation 3.57 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 10 (N= 853, 844, 852, 846) | 1.96 Units on a scale | Standard Deviation 3.24 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 3 (N= 935, 930, 936, 941) | 2.64 Units on a scale | Standard Deviation 3.82 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 24 (N= 758, 748, 737, 758) | 1.87 Units on a scale | Standard Deviation 3.47 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 1 (N= 984, 972, 989, 992) | 3.58 Units on a scale | Standard Deviation 4.25 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 16 (N= 784, 797, 775, 789) | 1.90 Units on a scale | Standard Deviation 3.43 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 5 (N= 911, 897, 906, 902) | 2.24 Units on a scale | Standard Deviation 3.52 |
| Bupropion 150 mg BID | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 13 (N= 797, 796, 789, 807) | 1.85 Units on a scale | Standard Deviation 3.22 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 13 (N= 797, 796, 789, 807) | 2.01 Units on a scale | Standard Deviation 3.47 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 1 (N= 984, 972, 989, 992) | 3.06 Units on a scale | Standard Deviation 3.87 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 2 (N= 961, 954, 963, 970) | 2.84 Units on a scale | Standard Deviation 3.85 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 3 (N= 935, 930, 936, 941) | 2.63 Units on a scale | Standard Deviation 3.93 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 4 (N= 923, 916, 934, 923) | 2.46 Units on a scale | Standard Deviation 3.8 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 5 (N= 911, 897, 906, 902) | 2.32 Units on a scale | Standard Deviation 3.86 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 6 (N= 899, 893, 909, 897) | 2.40 Units on a scale | Standard Deviation 3.87 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 8 (N= 868, 861, 877, 877) | 2.28 Units on a scale | Standard Deviation 3.6 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 10 (N= 853, 844, 852, 846) | 2.33 Units on a scale | Standard Deviation 3.8 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 12 (N= 772, 768, 750, 742) | 2.01 Units on a scale | Standard Deviation 3.51 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 16 (N= 784, 797, 775, 789) | 2.09 Units on a scale | Standard Deviation 3.61 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 20 (N= 771, 785, 762, 772) | 1.97 Units on a scale | Standard Deviation 3.53 |
| NRT Patch | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 24 (N= 758, 748, 737, 758) | 2.01 Units on a scale | Standard Deviation 3.45 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 6 (N= 899, 893, 909, 897) | 2.48 Units on a scale | Standard Deviation 3.97 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 13 (N= 797, 796, 789, 807) | 2.38 Units on a scale | Standard Deviation 4.27 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 4 (N= 923, 916, 934, 923) | 2.77 Units on a scale | Standard Deviation 4.21 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 3 (N= 935, 930, 936, 941) | 2.77 Units on a scale | Standard Deviation 3.94 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 5 (N= 911, 897, 906, 902) | 2.48 Units on a scale | Standard Deviation 3.92 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 16 (N= 784, 797, 775, 789) | 2.34 Units on a scale | Standard Deviation 3.98 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 1 (N= 984, 972, 989, 992) | 3.38 Units on a scale | Standard Deviation 4.2 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 24 (N= 758, 748, 737, 758) | 2.25 Units on a scale | Standard Deviation 4.04 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 20 (N= 771, 785, 762, 772) | 2.31 Units on a scale | Standard Deviation 4.15 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 10 (N= 853, 844, 852, 846) | 2.57 Units on a scale | Standard Deviation 4.41 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 8 (N= 868, 861, 877, 877) | 2.64 Units on a scale | Standard Deviation 4.29 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 2 (N= 961, 954, 963, 970) | 3.20 Units on a scale | Standard Deviation 4.25 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort | Week 12 (N= 772, 768, 750, 742) | 2.46 Units on a scale | Standard Deviation 4.1 |
Secondary
Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort
The primary safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 0.1 percentage of participants |
| Varenicline 1.0 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Overall (N= 2016, 2006, 2022, 2014) | 0.7 percentage of participants |
| Varenicline 1.0 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 1.4 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 0.4 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Overall (N= 2016, 2006, 2022, 2014) | 0.9 percentage of participants |
| Bupropion 150 mg BID | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 1.4 percentage of participants |
| NRT Patch | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 1.4 percentage of participants |
| NRT Patch | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 0.3 percentage of participants |
| NRT Patch | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Overall (N= 2016, 2006, 2022, 2014) | 0.8 percentage of participants |
| Placebo | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Non-psychiatric cohort (N= 990, 989, 1006, 999) | 0.5 percentage of participants |
| Placebo | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Overall (N= 2016, 2006, 2022, 2014) | 0.9 percentage of participants |
| Placebo | Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort | Psychiatric cohort (N= 1026, 1017, 1016, 1015) | 1.3 percentage of participants |
Secondary
Occurrence of the Components of NPS AE Primary Endpoint (Overall)
The NPS AE composite results (as previously described) are for the two cohorts combined and are presented below.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Mania | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Anxiety | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Panic Disorder | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Psychosis | 4 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Paranoia | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Feeling Abnormal | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Ideation | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hostility | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Agitation | 35 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicide | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Behavior | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Aggression | 17 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Depression | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Delusions | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hallucination | 6 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Homicidal Ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicide | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Mania | 10 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Behavior | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Psychosis | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Depression | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Panic Disorder | 20 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Ideation | 3 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Agitation | 40 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Homicidal Ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Paranoia | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hallucination | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Feeling Abnormal | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Anxiety | 5 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Delusions | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Aggression | 12 participants |
| Bupropion 150 mg BID | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hostility | 1 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hostility | 1 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Anxiety | 6 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Depression | 7 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Feeling Abnormal | 0 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Delusions | 2 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Agitation | 40 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Aggression | 9 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hallucination | 2 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Mania | 5 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Panic Disorder | 14 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Paranoia | 0 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Psychosis | 4 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Homicidal Ideation | 1 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Behavior | 1 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Ideation | 5 participants |
| NRT Patch | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicide | 0 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hallucination | 2 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Aggression | 11 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Anxiety | 5 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Homicidal Ideation | 0 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Agitation | 33 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Hostility | 0 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Delusions | 0 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Behavior | 1 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Feeling Abnormal | 0 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Depression | 6 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicide | 1 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Paranoia | 2 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Panic Disorder | 10 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Mania | 8 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Suicidal Ideation | 5 participants |
| Placebo | Occurrence of the Components of NPS AE Primary Endpoint (Overall) | Psychosis | 1 participants |
Secondary
Occurrence of the Components of Severe-only NPS AE Endpoint (Overall)
The NPS AE endpoint was the occurrence of at least 1 treatment-emergent severe AE of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least 1 treatment-emergent severe AE of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Agitation | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Feeling Abnormal | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Depression | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Homicidal Ideation | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Ideation | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Psychosis | 4 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Panic Disorder | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Paranoia | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hostility | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Mania | 2 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hallucination | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Behavior | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Delusions | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Aggression | 2 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicide | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Anxiety | 5 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Anxiety | 5 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Agitation | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Paranoia | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Depression | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Feeling Abnormal | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hostility | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Aggression | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Delusions | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hallucination | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Mania | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Panic Disorder | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Psychosis | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Behavior | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicide | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Homicidal Ideation | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Paranoia | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hallucination | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Homicidal Ideation | 1 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Psychosis | 4 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Depression | 7 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Mania | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Ideation | 1 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Aggression | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Feeling Abnormal | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Behavior | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hostility | 1 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicide | 0 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Anxiety | 6 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Agitation | 6 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Panic Disorder | 1 participants |
| NRT Patch | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Delusions | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Ideation | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Aggression | 1 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Delusions | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Psychosis | 1 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Feeling Abnormal | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Mania | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hallucination | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Panic Disorder | 2 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Paranoia | 2 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicide | 1 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Depression | 6 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Anxiety | 5 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Homicidal Ideation | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Hostility | 0 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Agitation | 2 participants |
| Placebo | Occurrence of the Components of Severe-only NPS AE Endpoint (Overall) | Suicidal Behavior | 1 participants |
Secondary
Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort
The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Each of these 16 components is reported below.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression (moderate and severe) | 3 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation (moderate and severe) | 10 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations (moderate and severe) | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety (severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility (severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression (severe) | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety (severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression (severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility (severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression (moderate and severe) | 3 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic (moderate and severe) | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation (moderate and severe) | 11 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression (moderate and severe) | 2 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation (moderate and severe) | 19 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation (moderate and severe) | 2 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania (moderate and severe) | 2 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility (severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression (severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety (severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic (moderate and severe) | 1 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression (severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania (moderate and severe) | 2 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation (moderate and severe) | 11 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety (severe) | 3 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression (moderate and severe) | 3 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide (moderate and severe) | 1 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation (moderate and severe) | 3 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic (moderate and severe) | 3 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility (severe) | 0 participants |
Secondary
Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort
The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Each of these 16 components is reported below.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety (severe) | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia (moderate and severe) | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Mania (moderate and severe) | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility (severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Panic (moderate and severe) | 7 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation (moderate and severe) | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations (moderate and severe) | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression (moderate and severe) | 14 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation (moderate and severe) | 25 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Depression (severe) | 6 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions (moderate and severe) | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis (moderate and severe) | 4 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations (moderate and severe) | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety (severe) | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility (severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation (moderate and severe) | 29 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Mania (moderate and severe) | 9 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis (moderate and severe) | 2 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior (moderate and severe) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Depression (severe) | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal (severe only) | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression (moderate and severe) | 9 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Panic (moderate and severe) | 16 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation (moderate and severe) | 2 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis (moderate and severe) | 3 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations (moderate and severe) | 2 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression (moderate and severe) | 7 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions (moderate and severe) | 1 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation (moderate and severe) | 3 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility (severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety (severe) | 6 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Depression (severe) | 7 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation (moderate and severe) | 21 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Mania (moderate and severe) | 3 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Panic (moderate and severe) | 13 participants |
| NRT Patch | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations (moderate and severe) | 2 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Depression (severe) | 6 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility (severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal (severe only) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis (moderate and severe) | 1 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions (moderate and severe) | 0 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation (moderate and severe) | 22 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior (moderate and severe) | 1 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Mania (moderate and severe) | 6 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation (moderate and severe) | 2 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression (moderate and severe) | 8 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia (moderate and severe) | 2 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety (severe) | 2 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Panic (moderate and severe) | 7 participants |
| Placebo | Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide (moderate and severe) | 0 participants |
Secondary
Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort
The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation | 2 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic | 1 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility | 1 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Agitation | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hallucinations | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Mania | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Homicidal ideation | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Anxiety | 3 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Depression | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Panic | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Hostility | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicide | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Delusions | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Paranoia | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Feeling abnormal | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal ideation | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Suicidal behavior | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Psychosis | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort | Aggression | 0 participants |
Secondary
Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort
The safety endpoint is the occurrence of at least one treatment emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent moderate or severe adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
Time frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Depression | 6 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety | 5 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Panic | 0 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Mania | 2 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation | 1 participants |
| Varenicline 1.0 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Depression | 4 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Mania | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Panic | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia | 0 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior | 1 participants |
| Bupropion 150 mg BID | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Mania | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis | 1 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation | 1 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety | 6 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Panic | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Depression | 7 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal | 0 participants |
| NRT Patch | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation | 4 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Feeling abnormal | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Aggression | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal behavior | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Delusions | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hallucinations | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Hostility | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Anxiety | 2 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Mania | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Panic | 1 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Agitation | 2 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicidal ideation | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Paranoia | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Depression | 6 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Psychosis | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Homicidal ideation | 0 participants |
| Placebo | Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort | Suicide | 0 participants |
Secondary
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort
The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit.The scale is also used to record any completed suicides.
Time frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 6 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 48 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Baseline) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 7 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 4 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Baseline) | 1 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 9 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 43 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 50 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Baseline) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 3 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 1 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 7 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 1 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 6 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 49 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Ideation (Baseline) | 1 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 6 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
Secondary
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall
The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides.
Time frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Baseline) | 6 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (treatment emergent 12 weeks) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Screening lifetime) | 386 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Screening lifetime) | 143 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (treatment emergent 12 weeks) | 34 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (treatment emergent 12 weeks) | 1 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Screening lifetime) | 152 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Screening lifetime) | 400 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Baseline) | 6 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (treatment emergent 12 weeks) | 19 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Screening lifetime) | 118 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Screening lifetime) | 383 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Baseline) | 2 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (treatment emergent 12 weeks) | 1 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (treatment emergent 12 weeks) | 23 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (treatment emergent 12 weeks) | 31 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (treatment emergent 12 weeks) | 3 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Screening lifetime) | 398 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Screening lifetime) | 129 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Ideation (Baseline) | 4 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall | Suicidal Behavior (Baseline) | 1 participants with positive responses |
Secondary
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort
The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from wish to be dead to active suicidal ideation with specific plan and intent. Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides.
Time frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Population: The safety dataset included all participants who had received at least one partial dose of study medication (N=8058) and was used to analyze all safety endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 137 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 338 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Baseline) | 6 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 0 participants with positive responses |
| Varenicline 1.0 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 27 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 15 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Baseline) | 5 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 143 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 357 participants with positive responses |
| Bupropion 150 mg BID | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 1 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 333 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Baseline) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Baseline) | 2 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 20 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 0 participants with positive responses |
| NRT Patch | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 111 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (treatment emergent 12 weeks) | 2 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (treatment emergent 12 weeks) | 25 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Screening lifetime) | 349 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Ideation (Baseline) | 3 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Screening lifetime) | 123 participants with positive responses |
| Placebo | Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort | Suicidal Behavior (Baseline) | 1 participants with positive responses |