Trial Outcomes & Findings for Safety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression (NCT NCT01078298)

Last Updated: 2013-04-16

Results Overview

Percentage of participants who reported no use of nicotine-containing products by answering "No" to the nicotine use inventory (NUI) questions: 'Has the participant smoked cigarettes' and 'Has the participant used other nicotine-containing products' in the last 7 days (Week 9) or since last study visit (Week 9 through 12) confirmed by a measurement of an end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

525 participants

Primary outcome timeframe

Week 9 through Week 12

Results posted on

2013-04-16

Participant Flow

Participant milestones

Participant milestones
Measure	Varenicline Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Overall Study STARTED	256	269
Overall Study COMPLETED	175	179
Overall Study NOT COMPLETED	81	90

Reasons for withdrawal

Reasons for withdrawal
Measure	Varenicline Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Overall Study Lost to Follow-up	12	13
Overall Study Withdrawal by Subject	31	33
Overall Study Protocol Violation	6	6
Overall Study Adverse Event	6	5
Overall Study Death	2	0
Overall Study Did not meet entrance criteria	0	1
Overall Study Other	24	32

Baseline Characteristics

Safety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Total n=525 Participants Total of all reporting groups
Age, Customized 18 to 44 years	106 participants n=5 Participants	98 participants n=7 Participants	204 participants n=5 Participants
Age, Customized 45 to 64 years	146 participants n=5 Participants	160 participants n=7 Participants	306 participants n=5 Participants
Age, Customized Greater than or equal to 65 years	4 participants n=5 Participants	11 participants n=7 Participants	15 participants n=5 Participants
Sex: Female, Male Female	159 Participants n=5 Participants	170 Participants n=7 Participants	329 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants	99 Participants n=7 Participants	196 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 9 through Week 12

Population: All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Percentage of Participants With a Four-Week Continuous Quit Rate (CQR)	35.9 Percentage of participants	15.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 9 through Week 24, Week 9 through Week 52

Population: All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.

Percentage of participants who remained abstinent from the period defined as start of the primary endpoint (Week 9) through Week 24 and the end of follow-up (Week 52) by reporting no use of nicotine-containing products confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Percentage of Participants With Continuous Abstinence Rate (CAR) Week 9 through Week 24	25.0 Percentage of participants	12.3 Percentage of participants
Percentage of Participants With Continuous Abstinence Rate (CAR) Week 9 through Week 52	20.3 Percentage of participants	10.4 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 12, 24, 52

Population: All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.

Number of participants reporting no use of nicotine-containing products in the last 7 days confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With 7-day Point Prevalence (PP) of Abstinence Week 12	118 participants	54 participants
Number of Participants With 7-day Point Prevalence (PP) of Abstinence Week 24	80 participants	49 participants
Number of Participants With 7-day Point Prevalence (PP) of Abstinence Week 52	73 participants	47 participants

SECONDARY outcome

Timeframe: Week 52

Population: All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.

Number of participants at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With 4-Week Point Prevalence (PP) of Abstinence	70 participants	45 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement.

Adverse Event (AE):any untoward medical occurrence attributed to study drug in participant who received study drug.SAE:AE causing:death;initial/prolonged inpatient hospitalization;life-threatening experience(immediate risk of dying);persistent/significant disability/incapacity;congenital anomaly.Solicited AEs collected by semi-structured neuropsychiatric AEs interview inquiring about AEs:delusions,hallucinations,paranoia,psychosis,mania,panic,agitation,hostility,aggression,homicidal ideation. If participant had positive response,investigator determined if it met AE criteria.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With Adverse Events (Including Solicited Neuropsychiatric Adverse Events)	185 participants	180 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52

Population: Safety analysis population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' is signifying those participants who were evaluated for this measure at the time point for each group respectively.

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement from baseline is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected

Outcome measures

Outcome measures
Measure	Varenicline n=250 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=263 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: much improved(n=241,248)	17 participants	14 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: minimally improved(n=241,248)	42 participants	45 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: no change(n=224,226)	139 participants	148 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: minimally improved(n=221,217)	37 participants	40 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 12: no change(n=210,204)	127 participants	124 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: much worse(n=211,200)	1 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: very much improved(n=188,188)	15 participants	19 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: no change(n=241,248)	146 participants	165 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: minimally worse(n=241,248)	26 participants	17 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: much worse(n=241,248)	0 participants	3 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: very much improved(n=230,245)	8 participants	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: much improved(n=230,245)	18 participants	12 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: minimally improved(n=230,245)	35 participants	51 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: no change(n=230,245)	152 participants	154 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: minimally worse(n=230,245)	15 participants	19 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 4: much worse(n=230,245)	2 participants	3 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: very much improved(n=227,233)	13 participants	9 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: much improved(n=227,233)	14 participants	11 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: minimally improved(n=227,233)	34 participants	46 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: no change(n=227,233)	146 participants	151 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: minimally worse(n=227,233)	19 participants	14 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 5: much worse(n=227,233)	1 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: very much improved(n=224,226)	11 participants	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: much improved(n=224,226)	20 participants	14 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: minimally improved(n=224,226)	39 participants	41 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: minimally worse(n=224,226)	13 participants	17 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 6: much worse(n=224,226)	2 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: very much improved(n=226,226)	19 participants	9 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: much improved(n=226,226)	23 participants	18 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: minimally improved(n=226,226)	32 participants	34 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: no change(n=226,226)	136 participants	150 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: minimally worse(n=226,226)	14 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 7: much worse(n=226,226)	2 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: very much improved(n=221,217)	19 participants	12 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: much improved(n=221,217)	18 participants	15 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: no change(n=221,217)	131 participants	139 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: minimally worse(n=221,217)	15 participants	10 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: much worse(n=221,217)	0 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 8: very much worse(n=221,217)	1 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 9: very much improved(n=218,214)	19 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 9: much improved(n=218,214)	19 participants	16 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 9: minimally improved(n=218,214)	36 participants	31 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 9: no change(n=218,214)	129 participants	141 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 9: minimally worse(n=218,214)	15 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: very much improved(n=212,211)	20 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: much improved(n=212,211)	21 participants	18 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: minimally improved(n=212,211)	30 participants	35 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: no change(n=212,211)	124 participants	133 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: minimally worse(n=212,211)	16 participants	11 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 10: much worse(n=212,211)	1 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: very much improved(n=211,205)	23 participants	15 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: much improved(n=211,205)	17 participants	14 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: minimally improved(n=211,205)	38 participants	35 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: no change(n=211,205)	120 participants	129 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: minimally worse(n=211,205)	13 participants	10 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 11: much worse(n=211,205)	0 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 12: very much improved(n=210,204)	19 participants	17 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 12: much improved(n=210,204)	19 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 12: minimally improved(n=210,204)	34 participants	39 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 12: minimally worse(n=210,204)	11 participants	11 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: very much improved(n=211,200)	18 participants	16 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: much improved(n=211,200)	19 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: minimally improved(n=211,200)	34 participants	40 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: no change(n=211,200)	127 participants	121 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 13: minimally worse(n=211,200)	12 participants	10 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: very much improved(n=203,199)	17 participants	15 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: much improved(n=203,199)	27 participants	16 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: minimally improved(n=203,199)	26 participants	33 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: no change(n=203,199)	119 participants	119 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: minimally worse(n=203,199)	14 participants	12 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 16: much worse(n=203,199)	0 participants	4 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: very much improved(n=196,193)	17 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: much improved(n=196,193)	17 participants	18 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: minimally improved(n=196,193)	24 participants	31 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: no change(n=196,193)	127 participants	125 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: minimally worse(n=196,193)	10 participants	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 24: much worse(n=196,193)	1 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: much improved(n=188,188)	19 participants	21 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: minimally improved(n=188,188)	27 participants	31 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: no change(n=188,188)	118 participants	113 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: minimally worse(n=188,188)	9 participants	3 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 32: much worse(n=188,188)	0 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: very much improved(n=180,182)	10 participants	17 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: much improved(n=180,182)	23 participants	15 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: minimally improved(n=180,182)	23 participants	32 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: no change(n=180,182)	117 participants	109 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: minimally worse(n=180,182)	6 participants	7 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: much worse(n=180,182)	0 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 40: very much worse(n=180,182)	1 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 52: very much improved(n=178,180)	20 participants	22 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 52: much improved(n=178,180)	20 participants	13 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 52: minimally improved(n=178,180)	25 participants	26 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 52: no change(n=178,180)	110 participants	112 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 52: minimally worse(n=178,180)	3 participants	7 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: very much improved(n=250,263)	1 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: much improved(n=250,263)	12 participants	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: minimally improved(n=250,263)	31 participants	21 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: no change(n=250,263)	189 participants	222 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: minimally worse(n=250,263)	16 participants	11 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 1: much worse(n=250,263)	1 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: very much improved(n=244,255)	2 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: much improved(n=244,255)	18 participants	12 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: minimally improved(n=244,255)	33 participants	38 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: no change(n=244,255)	159 participants	181 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: minimally worse(n=244,255)	27 participants	21 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 2: much worse(n=244,255)	5 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) Week 3: very much improved(n=241,248)	10 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. Here, the 'n' is signifying those participants who were evaluable for this measure at the specific categories for each arm group.

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 7:Mildly (n=226,225)	36 participants	37 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 7:Mildly (n=226,225)	10 participants	10 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 8:Borderline (n=221,216)	4 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 8:Borderline (n=221,216)	14 participants	19 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 1:Borderline (n=250,263)	2 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 1:Mildly (n=250,263)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 2:Moderately (n=244,254)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 2:Moderately (n=244,254)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 2:Moderately (n=244,254)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 2:Moderately (n=244,254)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline: Moderately; Week 2:Markedly (n=244,254)	3 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 2:Markedly (n=244,254)	1 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 3:Normal (n=241,247)	101 participants	95 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 3:Normal (n=241,247)	6 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 3:Normal (n=241,247)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 3:Borderline (n=241,247)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 3:Borderline (n=241,247)	4 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 3:Mildly (n=241,247)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 3:Mildly (n=241,247)	6 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 3:Mildly (n=241,247)	42 participants	42 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 3:Moderately (n=241,247)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 3:Moderately (n=241,247)	19 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 3:Moderately (n=241,247)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 3:Markedly (n=241,247)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 3:Markedly (n=241,247)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 4:Normal (n=230,244)	101 participants	92 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 4:Normal (n=230,244)	17 participants	17 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 4:Normal (n=230,244)	7 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 4:Borderline (n=230,244)	2 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 4:Borderline (n=230,244)	17 participants	27 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 4:Borderline (n=230,244)	8 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 4:Borderline (n=230,244)	1 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 4:Mildly (n=230,244)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 4:Mildly (n=230,244)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 4:Mildly (n=230,244)	39 participants	43 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 4:Mildly (n=230,244)	11 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 4:Moderately (n=230,244)	12 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 4:Moderately (n=230,244)	1 participants	18 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 4:Markedly (n=230,244)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 5:Normal (n=227,232)	98 participants	88 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 5:Normal (n=227,232)	19 participants	16 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 5:Borderline (n=227,232)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 5:Borderline (n=227,232)	13 participants	30 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 5:Borderline (n=227,232)	8 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 5:Borderline (n=227,232)	2 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 5:Mildly (n=227,232)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 5:Mildly (n=227,232)	6 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 5:Mildly (n=227,232)	11 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 5:Moderately (n=227,232)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 5:Moderately (n=227,232)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 5:Moderately (n=227,232)	2 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 5:Moderately (n=227,232)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 5:Markedly (n=227,232)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 6:Normal (n=224,225)	22 participants	18 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 6:Normal (n=224,225)	10 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 6:Normal (n=224,225)	3 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 6:Borderline (n=224,225)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 6:Borderline (n=224,225)	11 participants	24 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 6:Mildly (n=224,225)	5 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 6:Mildly (n=224,225)	38 participants	37 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 6:Mildly (n=224,225)	8 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 6:Mildly (n=224,225)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 6:Moderately (n=224,225)	0 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 6:Moderately (n=224,225)	1 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 6:Moderately (n=224,225)	10 participants	14 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 6:Markedly (n=224,225)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 6:Markedly (n=224,225)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 7:Normal (n=226,225)	23 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 7:Normal (n=226,225)	14 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 7:Borderline (n=226,225)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 7:Mildly (n=226,225)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 8:Borderline (n=221,216)	7 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 8:Borderline (n=221,216)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 8:Mildly (n=221,216)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 8:Mildly (n=221,216)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 8:Moderately (n=221,216)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 8:Moderately (n=221,216)	9 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 8:Moderately (n=221,216)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 8:Markedly (n=221,216)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 9:Normal (n=218,213)	91 participants	87 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 9:Normal (n=218,213)	4 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 9:Borderline (n=218,213)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 9:Borderline (n=218,213)	13 participants	19 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 9:Borderline (n=218,213)	6 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 9:Mildly (n=218,213)	10 participants	9 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 9:Markedly (n=218,213)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 9:Markedly (n=218,213)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 10:Normal (n=212,210)	13 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 10:Normal (n=212,210)	7 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 10:Borderline (n=212,210)	5 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 10:Mildly (n=212,210)	29 participants	35 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 10:Mildly (n=212,210)	8 participants	11 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 11:Mildly (n=211,205)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 11:Mildly (n=211,205)	2 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 11:Mildly (n=211,205)	30 participants	34 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 12:Normal (n=210,203)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 12:Borderline (n=210,203)	4 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 12:Borderline(n=210,203)	12 participants	16 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 12:Borderline (n=210,203)	6 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 12:Borderline (n=210,203)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 12:Mildly (n=210,203)	9 participants	14 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 12:Moderately(n=210,203)	8 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 12:Moderately(n=210,203)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 12:Markedly(n=210,203)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 13:Normal (n=211,199)	92 participants	78 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 13:Normal (n=211,199)	6 participants	9 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 13:Normal (n=211,199)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 13:Borderline(n=211,199)	5 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 13:Borderline(n=211,199)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 13:Mildly (n=211,199)	0 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 13:Moderately(n=211,199)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 16:Normal (n=203,198)	19 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 16:Normal (n=203,198)	14 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 16:Borderline (n=203,198)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 16:Borderline(n=203,198)	11 participants	16 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 16:Borderline (n=203,198)	4 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 16:Borderline(n=203,198)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 24:Moderately (n=196,192)	4 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 24:Moderately(n=196,192)	7 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 32:Borderline (n=188,187)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 52:Mildly (n=178,179)	24 participants	26 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 40:Borderline (n=180,181)	8 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 40:Borderline(n=180,181)	4 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 40:Borderline (n=180,181)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 40:Mildly (n=180,181)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 40:Mildly (n=180,181)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 1:Normal (n=250,263)	105 participants	100 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 1:Normal (n=250,263)	7 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 1:Normal (n=250,263)	4 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 1:Normal (n=250,263)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 1:Borderline (n=250,263)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 1:Borderline (n=250,263)	31 participants	42 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 1:Borderline (n=250,263)	9 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 1:Mildly (n=250,263)	4 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 1:Mildly (n=250,263)	46 participants	56 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 1:Mildly (n=250,263)	6 participants	9 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 1:Moderately (n=250,263)	1 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 1:Moderately (n=250,263)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 1:Moderately (n=250,263)	28 participants	30 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 1:Moderately (n=250,263)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 1:Markedly (n=250,263)	1 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 2:Normal (n=244,254)	102 participants	96 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 2:Normal (n=244,254)	13 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 2:Normal (n=244,254)	5 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline: Moderately; Week 2:Normal (n=244,254)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 2:Borderline (n=244,254)	1 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 2:Borderline (n=244,254)	22 participants	37 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 2:Borderline (n=244,254)	10 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 2:Borderline (n=244,254)	4 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 2:Mildly (n=244,254)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 2:Mildly (n=244,254)	4 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 2:Mildly (n=244,254)	40 participants	48 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 2:Mildly (n=244,254)	10 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 2:Mildly (n=244,254)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 2:Moderately (n=244,254)	20 participants	24 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 3:Normal (n=241,247)	18 participants	16 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 3:Borderline (n=241,247)	16 participants	34 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 3:Borderline (n=241,247)	8 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 3:Mildly (n=241,247)	10 participants	17 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 3:Mildly (n=241,247)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 3:Moderately (n=241,247)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 4:Normal (n=230,244)	4 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 4:Mildly (n=230,244)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 4:Moderately (n=230,244)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 4:Moderately (n=230,244)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 4:Markedly (n=230,244)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 4:Markedly (n=230,244)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 5:Normal (n=227,232)	8 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 5:Normal (n=227,232)	4 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 5:Mildly (n=227,232)	36 participants	39 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 5:Mildly (n=227,232)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 5:Moderately (n=227,232)	12 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 6:Normal (n=224,225)	96 participants	84 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 6:Borderline (n=224,225)	6 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 6:Borderline (n=224,225)	5 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 6:Mildly (n=224,225)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 6:Moderately (n=224,225)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 7:Normal (n=226,225)	93 participants	88 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 7:Normal (n=226,225)	3 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 7:Borderline (n=226,225)	5 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 7:Borderline (n=226,225)	13 participants	23 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 7:Borderline (n=226,225)	4 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 7:Borderline (n=226,225)	5 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 7:Mildly (n=226,225)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 7:Mildly (n=226,225)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 7:Moderately (n=226,225)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 7:Moderately (n=226,225)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 7:Moderately (n=226,225)	2 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 7:Moderately (n=226,225)	10 participants	14 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 7:Moderately (n=226,225)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 7:Markedly (n=226,225)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 8:Normal (n=221,216)	92 participants	87 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 8:Normal (n=221,216)	21 participants	19 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 8:Normal (n=221,216)	12 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 8:Normal (n=221,216)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 8:Borderline (n=221,216)	6 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 8:Mildly (n=221,216)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 8:Mildly (n=221,216)	32 participants	35 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 8:Mildly (n=221,216)	9 participants	13 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 8:Moderately (n=221,216)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 8:Markedly (n=221,216)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 9:Normal (n=218,213)	22 participants	18 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 9:Normal (n=218,213)	11 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 9:Borderline (n=218,213)	6 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 9:Borderline (n=218,213)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 9:Mildly (n=218,213)	3 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 9:Mildly (n=218,213)	2 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 9:Mildly (n=218,213)	34 participants	38 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 9:Moderately (n=218,213)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 9:Moderately (n=218,213)	8 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 9:Moderately (n=218,213)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 10:Normal (n=212,210)	88 participants	85 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 10:Normal (n=212,210)	20 participants	21 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 10:Borderline (n=212,210	14 participants	18 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 10:Borderline (n=212,210)	6 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 10:Borderline(n=212,210)	4 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 10:Borderline(n=212,210)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 10:Mildly (n=212,210)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 10:Mildly (n=212,210)	1 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 10:Moderately (n=212,210)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 10:Moderately (n=212,210)	3 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 10:Moderately(n=212,210)	9 participants	9 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 10:Moderately (n=212,210)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 10:Markedly (n=212,210)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 11:Normal (n=211,205)	90 participants	81 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 11:Normal (n=211,205)	23 participants	22 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 11:Normal (n=211,205)	13 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 11:Normal (n=211,205)	7 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 11:Normal (n=211,205)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 11:Borderline (n=211,205)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 11:Borderline(n=211,205)	10 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 11:Borderline (n=211,205)	6 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 11:Borderline(n=211,205)	3 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 11:Borderline (n=211,205)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 11:Mildly (n=211,205)	9 participants	13 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 11:Moderately (n=211,205)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 11:Moderately (n=211,205)	3 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 11:Moderately(n=211,205)	8 participants	10 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 11:Moderately (n=211,205)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 11:Markedly (n=211,205)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 12:Normal (n=210,203)	89 participants	79 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 12:Normal (n=210,203)	23 participants	22 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 12:Normal (n=210,203)	13 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 12:Normal (n=210,203)	6 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 12:Borderline(n=210,203)	4 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 12:Mildly (n=210,203)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 40:Mildly (n=180,181)	25 participants	28 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 12:Mildly (n=210,203)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 12:Mildly (n=210,203)	30 participants	34 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 12:Moderately(n=210,203)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 12:Moderately (n=210,203)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 13:Normal (n=211,199)	22 participants	21 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 13:Normal (n=211,199)	13 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 13:Borderline (n=211,199)	3 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 13:Borderline(n=211,199)	11 participants	17 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 13:Borderline (n=211,199)	7 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 13:Mildly (n=211,199)	30 participants	32 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 13:Mildly (n=211,199)	9 participants	11 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 13:Moderately (n=211,199)	3 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 13:Moderately(n=211,199)	7 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 13:Markedly (n=211,199)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 16:Normal (n=203,198)	91 participants	78 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 16:Normal (n=203,198)	7 participants	11 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 16:Normal (n=203,198)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 16:Borderline (n=203,198)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 16:Mildly (n=203,198)	1 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 16:Mildly (n=203,198)	0 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 16:Mildly (n=203,198)	30 participants	30 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 16:Mildly (n=203,198)	11 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 16:Moderately(n=203,198)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 16:Moderately (n=203,198)	3 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 16:Moderately(n=203,198)	4 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 16:Moderately (n=203,198)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 16:Markedly (n=203,198)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 24:Normal (n=196,192)	88 participants	78 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 24:Normal (n=196,192)	18 participants	19 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 24:Normal (n=196,192)	15 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 24:Normal (n=196,192)	5 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 24:Normal (n=196,192)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 24:Borderline (n=196,192)	0 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 24:Borderline(n=196,192)	13 participants	14 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 24:Borderline (n=196,192)	4 participants	6 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 24:Borderline(n=196,192)	2 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 24:Borderline (n=196,192)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 24:Mildly (n=196,192)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 24:Mildly (n=196,192)	0 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 24:Mildly (n=196,192)	27 participants	31 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 24:Mildly (n=196,192)	8 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 24:Moderately (n=196,192)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 24:Markedly (n=196,192)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 32:Normal (n=188,187)	82 participants	77 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 32:Normal (n=188,187)	16 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 32:Normal (n=188,187)	10 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 32:Normal (n=188,187)	4 participants	9 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 32:Normal (n=188,187)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 32:Borderline(n=188,187)	12 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 32:Borderline (n=188,187)	9 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 32:Borderline(n=188,187)	4 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 32:Borderline (n=188,187)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 32:Mildly (n=188,187)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 32:Mildly (n=188,187)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 32:Mildly (n=188,187)	28 participants	29 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 32:Mildly (n=188,187)	8 participants	11 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 32:Mildly (n=188,187)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 32:Moderately (n=188,187)	3 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 32:Moderately(n=188,187)	7 participants	5 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 32:Markedly (n=188,187)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 32:Markedly (n=188,187)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 40:Normal (n=180,181)	81 participants	71 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 40:Normal (n=180,181)	17 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 40:Normal (n=180,181)	11 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 40:Normal (n=180,181)	2 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 40:Normal (n=180,181)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 40:Borderline (n=180,181)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 40:Borderline(n=180,181)	9 participants	15 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 40:Mildly (n=180,181)	11 participants	12 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 40:Mildly (n=180,181)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 40:Moderately (n=180,181)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 40:Moderately (n=180,181)	2 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 40:Moderately(n=180,181)	4 participants	3 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 40:Markedly (n=180,181)	1 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 52:Normal (n=178,179)	81 participants	69 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 52:Normal (n=178,179)	19 participants	20 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 52:Normal (n=178,179)	12 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 52:Normal (n=178,179)	4 participants	7 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 52:Normal (n=178,179)	2 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 52:Borderline (n=178,179)	1 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 52:Borderline(n=178,179)	8 participants	14 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 52:Borderline (n=178,179)	8 participants	8 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 52:Borderline(n=178,179)	4 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 52:Borderline (n=178,179)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Normal; Week 52:Mildly (n=178,179)	1 participants	0 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Borderline; Week 52:Mildly (n=178,179)	0 participants	2 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 52:Mildly (n=178,179)	8 participants	11 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Mildly; Week 52:Moderately (n=178,179)	1 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 52:Moderately(n=178,179)	4 participants	4 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Markedly; Week 52:Moderately (n=178,179)	0 participants	1 participants
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score Baseline:Moderately; Week 52:Markedly (n=178,179)	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.

Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Change: mean score at observation minus mean score at baseline.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 7(n=226, 227)	-2.3 Units on a scale Standard Deviation 6.57	-2.4 Units on a scale Standard Deviation 5.94
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 8(n=221, 218)	-2.7 Units on a scale Standard Deviation 6.51	-2.6 Units on a scale Standard Deviation 6.02
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 9(n=218, 216)	-2.9 Units on a scale Standard Deviation 6.11	-2.5 Units on a scale Standard Deviation 6.55
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Baseline(n=256,269)	7.6 Units on a scale Standard Deviation 7.38	7.9 Units on a scale Standard Deviation 7.51
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 1(n=250,265)	-1.2 Units on a scale Standard Deviation 3.95	-0.6 Units on a scale Standard Deviation 4.17
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 2(n= 245, 255)	-1.0 Units on a scale Standard Deviation 6.06	-1.1 Units on a scale Standard Deviation 5.33
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 3(n= 241, 249)	-1.9 Units on a scale Standard Deviation 5.19	-1.8 Units on a scale Standard Deviation 4.96
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 4(n= 230, 246)	-2.2 Units on a scale Standard Deviation 5.62	-1.5 Units on a scale Standard Deviation 5.96
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 5(n=228, 235)	-2.1 Units on a scale Standard Deviation 6.01	-2.3 Units on a scale Standard Deviation 6.09
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 6(n=224, 227)	-2.2 Units on a scale Standard Deviation 6.15	-2.3 Units on a scale Standard Deviation 5.84
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 10(n=214, 212)	-2.9 Units on a scale Standard Deviation 6.21	-2.8 Units on a scale Standard Deviation 6.15
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 11(n= 211, 206)	-3.2 Units on a scale Standard Deviation 6.30	-2.9 Units on a scale Standard Deviation 6.13
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 12(n= 210, 205)	-3.4 Units on a scale Standard Deviation 6.20	-3.2 Units on a scale Standard Deviation 6.34
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 13(n= 211, 201)	-3.0 Units on a scale Standard Deviation 6.39	-3.6 Units on a scale Standard Deviation 5.88
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Change at Week 16(n= 202, 197)	-3.1 Units on a scale Standard Deviation 6.36	-3.2 Units on a scale Standard Deviation 6.61

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. Change: mean score at observation minus mean score at baseline.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 3(n= 241, 249)	-1.3 Units on a scale Standard Deviation 3.41	-1.2 Units on a scale Standard Deviation 3.68
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 11(n= 211, 206)	-2.3 Units on a scale Standard Deviation 4.48	-2.1 Units on a scale Standard Deviation 4.31
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 12(n= 210, 205)	-2.3 Units on a scale Standard Deviation 4.27	-2.4 Units on a scale Standard Deviation 4.47
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 13(n= 211, 201)	-2.4 Units on a scale Standard Deviation 4.49	-2.7 Units on a scale Standard Deviation 4.34
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 16(n= 202, 197)	-2.7 Units on a scale Standard Deviation 4.67	-2.5 Units on a scale Standard Deviation 4.28
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Baseline(n=256,269)	6.1 Units on a scale Standard Deviation 5.23	6.4 Units on a scale Standard Deviation 5.17
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 1(n=250,265)	-0.5 Units on a scale Standard Deviation 2.54	-0.7 Units on a scale Standard Deviation 3.15
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 2(n= 245, 255)	-0.7 Units on a scale Standard Deviation 3.98	-0.5 Units on a scale Standard Deviation 3.79
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 4(n= 230, 246)	-1.6 Units on a scale Standard Deviation 3.72	-1.2 Units on a scale Standard Deviation 3.87
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 5(n=228, 235)	-1.6 Units on a scale Standard Deviation 4.05	-1.6 Units on a scale Standard Deviation 4.00
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 6(n=224, 227)	-1.7 Units on a scale Standard Deviation 4.03	-1.6 Units on a scale Standard Deviation 4.00
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 7(n=226, 227)	-2.0 Units on a scale Standard Deviation 4.40	-1.8 Units on a scale Standard Deviation 4.32
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 8(n=221, 218)	-1.9 Units on a scale Standard Deviation 4.65	-1.9 Units on a scale Standard Deviation 4.10
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 9(n=218, 216)	-2.0 Units on a scale Standard Deviation 4.40	-1.9 Units on a scale Standard Deviation 3.94
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score Change at Week 10(n=214, 212)	-2.2 Units on a scale Standard Deviation 4.24	-2.0 Units on a scale Standard Deviation 4.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.

The BIS-11 is a self-administered 30 items questionnaire to assess measure of impulsivity. Items are scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Total score range from 30 to 120. Barratt suggested that a total score of greater than or equal to 75 could indicate an impulse-control disorder, whereas a total score in the range of 70 to 75 could indicate pathological impulsivity.

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Baseline(n=256,269)	65.1 Units on a scale Standard Deviation 6.42	64.2 Units on a scale Standard Deviation 7.30
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 16(n= 202, 196)	-1.4 Units on a scale Standard Deviation 6.25	-1.3 Units on a scale Standard Deviation 6.85
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 1(n=250,265)	-0.5 Units on a scale Standard Deviation 4.36	-0.8 Units on a scale Standard Deviation 4.26
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 2(n= 244, 255)	-0.8 Units on a scale Standard Deviation 4.73	-1.1 Units on a scale Standard Deviation 4.83
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 3(n= 241, 249)	-1.0 Units on a scale Standard Deviation 4.75	-1.3 Units on a scale Standard Deviation 4.81
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 4(n= 230, 246)	-1.0 Units on a scale Standard Deviation 5.19	-1.2 Units on a scale Standard Deviation 4.95
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 5(n=228, 234)	-1.1 Units on a scale Standard Deviation 5.27	-1.1 Units on a scale Standard Deviation 5.39
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 6(n=224, 226)	-1.4 Units on a scale Standard Deviation 5.28	-1.2 Units on a scale Standard Deviation 5.43
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 7(n=226, 227)	-1.6 Units on a scale Standard Deviation 5.62	-1.3 Units on a scale Standard Deviation 6.08
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 8(n=219, 216)	-1.3 Units on a scale Standard Deviation 5.81	-1.2 Units on a scale Standard Deviation 6.54
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 9(n=218, 215)	-1.5 Units on a scale Standard Deviation 6.25	-1.4 Units on a scale Standard Deviation 6.24
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 10(n=214, 211)	-1.5 Units on a scale Standard Deviation 6.13	-1.7 Units on a scale Standard Deviation 6.94
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 11(n= 211, 205)	-1.6 Units on a scale Standard Deviation 6.24	-1.5 Units on a scale Standard Deviation 6.78
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 12(n= 210, 204)	-1.0 Units on a scale Standard Deviation 6.55	-1.4 Units on a scale Standard Deviation 7.31
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score Change at Week 13(n= 211, 201)	-1.4 Units on a scale Standard Deviation 6.52	-1.1 Units on a scale Standard Deviation 7.00

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1 up to 30 days after Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (follow-up [FU])

Population: Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement.

C-SSRS assessed if participant experienced following: completed suicide (1), suicide attempt (2)(response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4)("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

Outcome measures

Outcome measures
Measure	Varenicline n=256 Participants Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 Participants Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline,Suicidal Behavior or/and Ideation	6 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline,4: wish to be dead	6 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4: with any methods,without intent to act	2 participants	5 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4: with specific plan and intent	0 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,4: with some intent,without specific plan	1 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,7	1 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline,4	6 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,Suicidal Behavior or/and Ideation	15 participants	20 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,2	0 participants	1 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4	15 participants	19 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4: wish to be dead	15 participants	18 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4: non-specific active suicidal thoughts	4 participants	7 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) TE,4: with some intent,without specific plan.	0 participants	3 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,Suicidal Behavior or/and Ideation	13 participants	12 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,1	1 participants	0 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,4	12 participants	12 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,4: wish to be dead	11 participants	12 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,4: non-specific active suicidal thoughts	5 participants	3 participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) FU,4: with any methods,without intent to act	2 participants	2 participants

Adverse Events

Varenicline

Serious events: 7 serious events

Other events: 158 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 126 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Varenicline n=256 participants at risk Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 participants at risk Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Cardiac disorders Palpitations	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Acute abdomen	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Device dislocation	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Autoimmune hepatitis	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Device related infection	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fractured coccyx	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Ligament laxity	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Agitation	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression suicidal	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Intentional sefl-injury	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Psychotic disorder	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Claculus ureteric	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 1/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Haemodynamic instability	0.39% 1/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Measure	Varenicline n=256 participants at risk Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.	Placebo n=269 participants at risk Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
Gastrointestinal disorders Constipation	5.9% 15/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 9/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	6.2% 16/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 12/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	6.6% 17/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.2% 14/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	27.0% 69/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.4% 28/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	5.1% 13/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 9/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Irritability	10.9% 28/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 22/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	5.5% 14/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 13/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	5.9% 15/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 13/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	5.5% 14/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.9% 5/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	16.8% 43/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.2% 30/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Abnormal dreams	11.3% 29/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 22/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Agitation	6.6% 17/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.7% 10/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	7.0% 18/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.3% 25/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	6.6% 17/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 13/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	10.9% 28/256 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 13/269 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.