Trial Outcomes & Findings for Randomized Study Comparing the Efficacy and Safety of Varenicline Tartrate to Placebo in Smoking Cessation When Subjects Are Allowed to Set Their Own Quit Date (NCT NCT00691483)

Last Updated: 2015-11-20

Results Overview

The percentage of participants who reported complete abstinence from cigarette smoking and other nicotine use (on the Nicotine Use Inventory) and who did not have carbon monoxide (CO) \>10 parts per million (ppm) at any visits Week 9 through Week 12. A participant was considered a responder if they met the following criterion: said they had not smoked or used nicotine products 'since the last visit' and did not have CO \>10 ppm.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

659 participants

Primary outcome timeframe

Week 9 through Week 12

Results posted on

2015-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	Varenicline Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo Placebo matched to varenicline.
Overall Study STARTED	493	166
Overall Study Received Treatment	486	165
Overall Study COMPLETED	425	141
Overall Study NOT COMPLETED	68	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Varenicline Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo Placebo matched to varenicline.
Overall Study Adverse Event	14	6
Overall Study Lost to Follow-up	17	10
Overall Study Withdrawal by Subject	24	7
Overall Study Other known cause	6	1
Overall Study Randomized by not treated	7	1

Baseline Characteristics

Randomized Study Comparing the Efficacy and Safety of Varenicline Tartrate to Placebo in Smoking Cessation When Subjects Are Allowed to Set Their Own Quit Date

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.	Total n=651 Participants Total of all reporting groups
Age, Customized Between 18 and 44 years	248 Participants n=93 Participants	93 Participants n=4 Participants	341 Participants n=27 Participants
Age, Customized Between 45 and 64 years	209 Participants n=93 Participants	64 Participants n=4 Participants	273 Participants n=27 Participants
Age, Customized >= 65 years	29 Participants n=93 Participants	8 Participants n=4 Participants	37 Participants n=27 Participants
Sex: Female, Male Female	193 Participants n=93 Participants	66 Participants n=4 Participants	259 Participants n=27 Participants
Sex: Female, Male Male	293 Participants n=93 Participants	99 Participants n=4 Participants	392 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 9 through Week 12

Population: Full analysis set (FAS): took at least 1 dose, including partial doses, of randomized study drug. Missing CO measurements imputed as =\<10 ppm. Missing visit(s) imputed based on next available visit. Subjects who discontinued study and were lost to follow up were assumed smokers. Missing data not imputed from other weekly interview questions.

Outcome measures

Outcome measures
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.
Percentage of Participants With 4-week Continuous Abstinence (CA)	53.9 Percentage of participants	19.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 9 through Week 24

Population: FAS. Missing CO measurements imputed as =\<10 ppm. Missing visit(s) imputed based on next available visit. Subjects who discontinued study and were lost to follow up were assumed smokers. Missing data not imputed from other weekly interview questions.

Percentage of participants with CA from cigarette smoking and other nicotine-containing (treatment phase) or tobacco (non-treatment phase) products use, who did not have CO \>10 ppm at any visits Week 9 through Week 24. A participant was considered a responder if they met the following criterion: said they had not smoked or used nicotine products 'since the last visit' and did not have CO \>10 ppm.

Outcome measures

Outcome measures
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.
Percentage of Participants With Continuous Abstinence (CA) From Smoking Weeks 9-24	35.2 Percentage of participants	12.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 9 through Week 24

Population: FAS. If the number of days smoked was missing for a subject visit, the CA responder status of the subject at that visit determined the imputation.

Responder for the primary endpoint of CA from Week 9 through Week 12 and who had no more than 6 days of smoking during the non-treatment phase of the study. For Weeks 13, 16, 20, and 24, long term quit was determined by CO-confirmed in-clinic visit.

Outcome measures

Outcome measures
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.
Percentage of Participants With Long Term Quit Through Week 24	40.7 Percentage of participants	14.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 12 and Week 24

Population: FAS. Missing weekly interview questions of whether the subject had "smoked in the last 7 days" were not imputed; missing CO was imputed as =\<10 ppm.

Percentage of participants with complete abstinence from cigarette smoking or other nicotine-containing (treatment phase) or tobacco (non-treatment phase) products use for the 7 days prior to Week 12 and Week 24, respectively, who did not have CO \>10 ppm at any visits. CO-confirmed in-clinic visit.

Outcome measures

Outcome measures
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.
Percentage of Participants With 7-day Point Prevalence of Nonsmoking (Smoking Cessation) Week 12	59.5 Percentage of participants	24.2 Percentage of participants
Percentage of Participants With 7-day Point Prevalence of Nonsmoking (Smoking Cessation) Week 24	43.0 Percentage of participants	17.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: FAS. Missing inventory interview questions of whether the subject had "smoked or used any other tobacco products" in the last 4 weeks were not imputed. Missing CO was imputed as =\<10 ppm.

Percentage of participants with complete abstinence from cigarette smoking or use of tobacco products for the 4 weeks prior to Week 24 who did not have CO \>10 ppm at any visits.

Outcome measures

Outcome measures
Measure	Varenicline n=486 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 Participants Placebo matched to varenicline.
Percentage of Participants With 4-week Point Prevalence of Nonsmoking	42.0 Percentage of participants	17.0 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through Week 5

Population: Number of participants analyzed = participants with FQA through Week 5, excluding 157 participants for whom FTND was not done at the time of FQA (1 participant also had inconsistent FQA date with first dosing date). Analysis done by smoking status at Week 12 (Responder for the primary endpoint of CA Weeks 9-12).

Change in nicotine dependence from baseline to the date of the FQA within the first 5 weeks. FTND was designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. It contains items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. The FTND contains 4 yes-no and 2 multiple choice questions and can be used in a self-report format. The items on FTND are scored 0 to 3 for multiple choice items, the items are summed to yield a total score of 0-10 (0=minimum nicotine dependence; 10=maximum nicotine dependence).

Outcome measures

Outcome measures
Measure	Varenicline n=276 Participants Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=79 Participants Placebo matched to varenicline.
Change From Baseline in Fagerström Test for Nicotine Dependence (FTND) to Day of First Quit Attempt (FQA) Through Week 5 by Smoking Status at Weeks 9-12 Responders	-2.3 Units on a scale Standard Deviation 2.53	-1.8 Units on a scale Standard Deviation 1.95
Change From Baseline in Fagerström Test for Nicotine Dependence (FTND) to Day of First Quit Attempt (FQA) Through Week 5 by Smoking Status at Weeks 9-12 Non-Responders	-2.5 Units on a scale Standard Deviation 2.55	-1.8 Units on a scale Standard Deviation 2.13

Adverse Events

Varenicline

Serious events: 6 serious events

Other events: 297 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Varenicline n=486 participants at risk Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.	Placebo n=165 participants at risk Placebo matched to varenicline.
Musculoskeletal and connective tissue disorders Intervertebral disc protrustion	0.41% 2/486 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% 0/165 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 Carotid artery stenosis	0.21% 1/486 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% 0/165 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 Syncope	0.21% 1/486 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% 0/165 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 Suicidal ideation	0.00% 0/486 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.	0.61% 1/165 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 Calculus ureteric	0.21% 1/486 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% 0/165 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 Pyelocaliectasis	0.21% 1/486 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% 0/165 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 Ureteric obstruction	0.21% 1/486 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% 0/165 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 Peripheral arterial occlusive disease	0.21% 1/486 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% 0/165 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.

Other adverse events

Additional Information

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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.
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Restriction type: OTHER