Trial Outcomes & Findings for Extended Varenicline Treatment for Smoking Among Cancer Patients (NCT NCT01756885)

NCT ID: NCT01756885

Last Updated: 2019-07-30

Results Overview

Number of Participants with Verified 7 Day Tobacco Abstinence.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

207 participants

Primary outcome timeframe

Weeks 24 & 52

Results posted on

2019-07-30

Participant Flow

Participant milestones

Participant milestones
Measure	Standard Varenicline Treatment 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
Overall Study STARTED	102	105
Overall Study COMPLETED	79	79
Overall Study NOT COMPLETED	23	26

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Extended Varenicline Treatment for Smoking Among Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Varenicline Treatment n=102 Participants 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=105 Participants 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling	Total n=207 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	82 Participants n=5 Participants	81 Participants n=7 Participants	163 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants
Age, Continuous	60.0 years STANDARD_DEVIATION 9.5 • n=5 Participants	58.00 years STANDARD_DEVIATION 9.4 • n=7 Participants	58.5 years STANDARD_DEVIATION 9.4 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	59 Participants n=7 Participants	105 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	46 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	100 Participants n=7 Participants	196 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) White	72 Participants n=5 Participants	72 Participants n=7 Participants	144 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	102 participants n=5 Participants	105 participants n=7 Participants	207 participants n=5 Participants
Fagerström Test for Nicotine Dependence	4.6 units on a scale STANDARD_DEVIATION 2.2 • n=5 Participants	4.4 units on a scale STANDARD_DEVIATION 2.1 • n=7 Participants	4.5 units on a scale STANDARD_DEVIATION 2.1 • n=5 Participants
Karnofsky Performance Score	91.7 units on a scale STANDARD_DEVIATION 11.7 • n=5 Participants	92.1 units on a scale STANDARD_DEVIATION 10.9 • n=7 Participants	91.9 units on a scale STANDARD_DEVIATION 11.2 • n=5 Participants
ECOG Performance Status	0.25 units on a scale STANDARD_DEVIATION 0.43 • n=5 Participants	0.25 units on a scale STANDARD_DEVIATION 0.44 • n=7 Participants	0.25 units on a scale STANDARD_DEVIATION 0.43 • n=5 Participants
Breath carbon monoxide	18.2 units on a scale STANDARD_DEVIATION 11.3 • n=5 Participants	19.7 units on a scale STANDARD_DEVIATION 11.0 • n=7 Participants	19.0 units on a scale STANDARD_DEVIATION 11.1 • n=5 Participants

PRIMARY outcome

Timeframe: Weeks 24 & 52

Number of Participants with Verified 7 Day Tobacco Abstinence.

Outcome measures

Outcome measures
Measure	Standard Varenicline Treatment n=102 Participants 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=105 Participants 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
7-day CO-verified Tobacco Abstinence Week 24	28 participants	32 participants
7-day CO-verified Tobacco Abstinence Week 52	16 participants	17 participants

SECONDARY outcome

Timeframe: Weeks 24 & 52

Population: Difference in number of participants at Weeks 24 and 52 are due to attrition.

The Short-Form Health Survey (SF-12) assesses Quality of Life (QOL). Scale range from 12 - 47. Higher score indicates worse quality of life.

Outcome measures

Outcome measures
Measure	Standard Varenicline Treatment n=52 Participants 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=56 Participants 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
Quality of Life at Week 24 and 52 Week 24	38.75 score on a scale Standard Deviation 6.17	38.46 score on a scale Standard Deviation 5.90
Quality of Life at Week 24 and 52 Week 52	38.06 score on a scale Standard Deviation 6.81	36.91 score on a scale Standard Deviation 6.30

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 12, 24, and 52

No smoking from baseline to time-point, after a 2-week grace period.

Outcome measures

Outcome measures
Measure	Standard Varenicline Treatment n=102 Participants 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=105 Participants 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
Number of Participants With Continuous Abstinence Week 24	19 participants	22 participants
Number of Participants With Continuous Abstinence Week 52	11 participants	16 participants

Adverse Events

Standard Varenicline Treatment

Serious events: 9 serious events

Other events: 27 other events

Deaths: 4 deaths

Extended Varenicline Treatment

Serious events: 13 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Robert Schnoll

University of Pennsylvania

Phone: 215-746-7143

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Standard Varenicline Treatment n=102 participants at risk 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=105 participants at risk 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
Metabolism and nutrition disorders Dehydration, fluid build-up	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Dysphagia and difficulty breathing	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Facial edema	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Fever and swelling	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Hernia	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Confusion	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Abdominal pain	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	1.9% 2/105 • Number of events 2 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Anxiety (panic) attack	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Constipation and bleeding	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders COPD	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Infections and infestations Pneumonia	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second cancer	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Chest pain	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Injury, poisoning and procedural complications Radiation burn infection	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Nervous system disorders Seizure	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Abdominal abscess	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Injury, poisoning and procedural complications Cracked ribs	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Injury, poisoning and procedural complications Acute kidney injury	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Vascular disorders Deep vein thrombosis	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Injury, poisoning and procedural complications Injury from fall	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Headaches	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Death	3.9% 4/102 • Number of events 4 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer progression	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Blood and lymphatic system disorders Blood loss	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Cardiac disorders Atrial fibrillation	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Blood and lymphatic system disorders Anemia	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Renal and urinary disorders Bladder perforation	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Infections and infestations Enterocolotis infection	0.98% 1/102 • Number of events 2 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Infections and infestations Pelvic infection	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Reproductive system and breast disorders Prostatic obstruction	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Blood and lymphatic system disorders Sepsis	0.98% 1/102 • Number of events 1 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.

Other adverse events
Measure	Standard Varenicline Treatment n=102 participants at risk 12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Days 85-168: Placebo - 1.0mg twice daily orally Varenicline Placebo Smoking Cessation Counseling	Extended Varenicline Treatment n=105 participants at risk 24 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally Varenicline Smoking Cessation Counseling
General disorders Weakness	2.0% 2/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Skin and subcutaneous tissue disorders Skin swelling, rash, or redness	2.9% 3/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Depression	20.6% 21/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	19.0% 20/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Respiratory infection	2.0% 2/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer recurrence	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Suicidality	2.0% 2/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Nausea, abdominal pain	5.9% 6/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	3.8% 4/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Irritability	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Anxiety	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	1.9% 2/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Agitation	3.9% 4/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	8.6% 9/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Psychiatric disorders Hostility	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	6.7% 7/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Blood and lymphatic system disorders High cholesterol	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Skin and subcutaneous tissue disorders Hemorrhoids	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Cardiac disorders Heart attack	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Headache	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	1.9% 2/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Dizziness	2.9% 3/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Gout (worsening)	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Pins and needles feeling	0.00% 0/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.95% 1/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
General disorders Fainting	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.9% 3/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Asthma attack	2.9% 3/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Cholecytstosis	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Gastrointestinal disorders Cirrhosis	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Nervous system disorders Bracial plexopathy	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Eye disorders Blurred vision	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Renal and urinary disorders Acute kidney injury	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Endocrine disorders Hyperglycemia	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.
Vascular disorders Arterial injury	0.98% 1/102 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.	0.00% 0/105 • 53 weeks Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.