Trial Outcomes & Findings for Smoking-Cessation and Stimulant Treatment (S-CAST) (NCT NCT01077024)

Last Updated: 2021-09-29

Results Overview

Stimulant-free week results (no cocaine, methamphetamine and amphetamine use) were obtained by combining the urine drug screens (UDS) and the self-reported Timeline Follow-Back (TLFB). At the group level, this outcome translates into the percentage of weeks in each study arm that are stimulant-free.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

538 participants

Primary outcome timeframe

Week 16

Results posted on

2021-09-29

Participant Flow

Participant milestones

Participant milestones
Measure	Smoking-cessation Treatment + Substance Treatment as Usual Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Overall Study STARTED	267	271
Overall Study COMPLETED	236	243
Overall Study NOT COMPLETED	31	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Smoking-cessation Treatment + Substance Treatment as Usual Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Overall Study Lost to Follow-up	20	14
Overall Study Withdrawal by Subject	0	2
Overall Study Incarcerated	7	8
Overall Study Other	4	4

Baseline Characteristics

Smoking-Cessation and Stimulant Treatment (S-CAST)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.	Total n=538 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	266 Participants n=5 Participants	271 Participants n=7 Participants	537 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	136 Participants n=7 Participants	258 Participants n=5 Participants
Sex: Female, Male Male	145 Participants n=5 Participants	135 Participants n=7 Participants	280 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	83 Participants n=5 Participants	88 Participants n=7 Participants	171 Participants n=5 Participants
Race (NIH/OMB) White	162 Participants n=5 Participants	158 Participants n=7 Participants	320 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	230 Participants n=5 Participants	236 Participants n=7 Participants	466 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	267 participants n=5 Participants	271 participants n=7 Participants	538 participants n=5 Participants
Weight	184.8 pounds STANDARD_DEVIATION 43.77 • n=5 Participants	183.3 pounds STANDARD_DEVIATION 44.21 • n=7 Participants	184.0 pounds STANDARD_DEVIATION 43.96 • n=5 Participants

PRIMARY outcome

Timeframe: Week 16

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Stimulant-free Weeks Assessed by Self-report and Twice-weekly Urine Drug Screens	77.7 percentage of weeks Interval 0.694 to 1.3196	78.0 percentage of weeks Interval 0.694 to 1.3196

SECONDARY outcome

Timeframe: Week 10 assessment

point-prevalence abstinence defined as not smoking in the previous seven days based on self-report and confirmed with a Carbon Monoxide (CO) level ≤ 8 ppm

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Point-prevalence Abstinence (Smoking Outcome)	25.5 percentage of participants	2.2 percentage of participants

SECONDARY outcome

Timeframe: Post-quit days 15-42

A combination of daily self-reported smoking data and weekly carbon monoxide levels were used to determine continuous abstinence during post-quit days 15 - 42.

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Four Week Continuous Smoking Abstinence	6.7 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 3-month follow-up visit

Population: This outcome was only compared for participants who attended the 3-month follow-up visit (n=226 and n=240, respectively).

At the 3-month follow-up visit, percentage of participants with a negative urine drug screen for stimulant use and no stimulant use days reported during the past 28 days based on Timeline Follow-back.

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=226 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=240 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Stimulant-free Results at 3-month Visit	74.3 percentage of participants	68.8 percentage of participants

SECONDARY outcome

Timeframe: 3- month follow-up visits

point-prevalence abstinence defined as not smoking in the previous seven days based on self-report and confirmed with a Carbon Monoxide (CO) level ≤ 8 ppm

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Point-prevalence Abstinence (Smoking Outcome) 3 Month Visit	19.1 percentage of participants	3.0 percentage of participants

SECONDARY outcome

Timeframe: 6 - months follow-up visit

Population: This outcome was only compared for participants who attended the 6-month follow-up visit (n=210 and n=218, respectively).

At the 6-month follow-up visit, percentage of participants with a negative urine drug screen for stimulant use and no stimulant use days reported during the past 28 days based on Timeline Follow-back.

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=210 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=218 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Stimulant-free Results at 6-month Visit	69.5 percentage of participants	71.6 percentage of participants

SECONDARY outcome

Timeframe: 6 month visit

point-prevalence abstinence defined as not smoking in the previous seven days based on self-report and confirmed with a Carbon Monoxide (CO) level ≤ 8 ppm

Outcome measures

Outcome measures
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 Participants Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 Participants Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Point-prevalence Abstinence (Smoking Outcome) 6 Month Visit	13.1 percentage of participants	3.7 percentage of participants

Adverse Events

Smoking-cessation Treatment + Substance Treatment as Usual

Serious events: 14 serious events

Other events: 181 other events

Deaths: 0 deaths

Substance-treatment as Usual

Serious events: 9 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 participants at risk Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 participants at risk Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Gastrointestinal disorders Dry mouth	5.2% 14/267 • Number of events 14 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Gastrointestinal disorders Nausea	6.7% 18/267 • Number of events 18 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	2.6% 7/271 • Number of events 7 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Gastrointestinal disorders Toothache	5.2% 14/267 • Number of events 14 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	5.5% 15/271 • Number of events 15 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Nasopharyngitis	7.1% 19/267 • Number of events 19 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	7.0% 19/271 • Number of events 19 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Sinusitis	3.4% 9/267 • Number of events 9 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	5.2% 14/271 • Number of events 14 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Upper respiratory tract infection	6.0% 16/267 • Number of events 16 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	4.8% 13/271 • Number of events 13 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Nervous system disorders Headache	12.7% 34/267 • Number of events 34 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	4.8% 13/271 • Number of events 13 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Anxiety	7.5% 20/267 • Number of events 20 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	1.8% 5/271 • Number of events 5 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Insomnia	7.9% 21/267 • Number of events 21 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	1.1% 3/271 • Number of events 3 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Respiratory, thoracic and mediastinal disorders Throat irritation	6.0% 16/267 • Number of events 16 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.

Additional Information

Dr. Theresa Winhusen

University of Cincinnati Addiction Sciences Division

Phone: 513-585-8227

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Smoking-cessation Treatment + Substance Treatment as Usual n=267 participants at risk Smoking-cessation treatment: Smoking cessation treatment includes four components: 1. brief weekly individual smoking-cessation counseling study weeks 1-10; 2. extended-release (XL) bupropion (300 mg/day)study weeks 1-10; 3. nicotine inhaler (6-16 cartridges per day ad libitum)during the post-quit treatment phase; 4. prize-based contingency management during the post-quit treatment phase.	Substance-treatment as Usual n=271 participants at risk Treatment as usual is outpatient stimulant-dependence treatment as typically provided by the participating site.
Cardiac disorders Angina Pectoris	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.74% 2/271 • Number of events 2 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Cardiac disorders Myocardial Infarction	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Eye disorders Vision blurred	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Gastrointestinal disorders Constiipation	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Gastrointestinal disorders Pancreatitis	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
General disorders Chest pain	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
General disorders Death	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
General disorders Drug withdrawal syndrome	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
General disorders Non-cardiac chest pain	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Appendicitis	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Pyelonephritis	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Sepsis	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Infections and infestations Sinusitis	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Injury, poisoning and procedural complications Tibia fracture	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Metabolism and nutrition disorders Dehydration	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Musculoskeletal and connective tissue disorders Exostosis	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Depression	0.75% 2/267 • Number of events 2 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Panic Attack	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Suicidal ideation	0.75% 2/267 • Number of events 2 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Psychiatric disorders Suicide attempt	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/267 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.37% 1/271 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.
Vascular disorders Haematoma	0.37% 1/267 • Number of events 1 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.	0.00% 0/271 • A systematic collection of adverse events occurred from the time of consent to the 10th week final visit. Serious adverse events discovered unsystematically were collected through 30 days following the 10th week final visit. Investigators systematically interviewed participants at each study week regarding any untoward events occurring since the last study visit.