Trial Outcomes & Findings for Reduced Nicotine Content Cigarettes in Smokers of Lower Socioeconomic Status (NCT NCT01928719)

NCT ID: NCT01928719

Last Updated: 2019-05-01

Results Overview

Adherence to the regimen was assessed via dropout (due to withdrawal or lost-to-follow up) during the randomized intervention trial phase of the study. Dropout was analyzed as a time-to-event outcome during the 18 weeks after randomization.

Recruitment status

COMPLETED

Study phase

Target enrollment

280 participants

Primary outcome timeframe

18 weeks

Results posted on

2019-05-01

Participant Flow

Participants completed a baseline phase of one week on usual brand cigarettes and another baseline phase on same nicotine content cigarettes (2 weeks). Of these, 35 participants either were lost to follow up or withdrawn from the study during the baseline phase and before they started the intervention.

Participant milestones

Participant milestones
Measure	Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Overall Study STARTED	122	123
Overall Study COMPLETED	70	104
Overall Study NOT COMPLETED	52	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Overall Study Lost to Follow-up	26	11
Overall Study Withdrawal by Subject	22	7
Overall Study Protocol Violation	3	1
Overall Study Adverse Event	1	0

Baseline Characteristics

Reduced Nicotine Content Cigarettes in Smokers of Lower Socioeconomic Status

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette	Total n=245 Participants Total of all reporting groups
Age, Continuous	44.7 years STANDARD_DEVIATION 12.1 • n=5 Participants	45.1 years STANDARD_DEVIATION 10.8 • n=7 Participants	44.9 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	72 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	51 Participants n=7 Participants	117 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	117 Participants n=5 Participants	120 Participants n=7 Participants	237 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/white	71 Participants n=5 Participants	82 Participants n=7 Participants	153 Participants n=5 Participants
Race/Ethnicity, Customized African American/black	43 Participants n=5 Participants	35 Participants n=7 Participants	78 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Island	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan native	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	122 participants n=5 Participants	123 participants n=7 Participants	245 participants n=5 Participants
Education < High School Degree	15 Participants n=5 Participants	25 Participants n=7 Participants	40 Participants n=5 Participants
Education High School Degree	55 Participants n=5 Participants	57 Participants n=7 Participants	112 Participants n=5 Participants
Education > High School Degree and < Bachelor's degree	52 Participants n=5 Participants	41 Participants n=7 Participants	93 Participants n=5 Participants
Cigarettes per Day	24.2 cigarettes STANDARD_DEVIATION 11 • n=5 Participants	24 cigarettes STANDARD_DEVIATION 13.9 • n=7 Participants	24.1 cigarettes STANDARD_DEVIATION 12.5 • n=5 Participants
Plasma Cotinine	261.6 ng/ml STANDARD_DEVIATION 148.6 • n=5 Participants	260.3 ng/ml STANDARD_DEVIATION 148.5 • n=7 Participants	260.9 ng/ml STANDARD_DEVIATION 148.3 • n=5 Participants
Exhaled Carbon Monoxide	31.5 parts per million STANDARD_DEVIATION 17.2 • n=5 Participants	31.3 parts per million STANDARD_DEVIATION 15.8 • n=7 Participants	31.4 parts per million STANDARD_DEVIATION 16.5 • n=5 Participants
Perceived Stress Scale Score	12.6 units on a scale STANDARD_DEVIATION 6.7 • n=5 Participants	12.1 units on a scale STANDARD_DEVIATION 7.2 • n=7 Participants	12.3 units on a scale STANDARD_DEVIATION 6.9 • n=5 Participants
Menthol smoker	85 Participants n=5 Participants	85 Participants n=7 Participants	170 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 weeks

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Number of Participants Who Dropped Out of Study as a Measure of Adherence	52 Participants	19 Participants

SECONDARY outcome

Timeframe: 18 weeks

Population: Participants (who were randomized) are stratified according to the listed characteristics.

Baseline participant characteristics were evaluated for their association with the primary outcome, randomized trial phase dropout. The table below reports the number of participants who dropped out by each characteristic that was found to be univariately associated with the primary outcome.

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=245 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Predictors of Participant Dropout Reduced Nicotine Content Group	52 Participants	—
Predictors of Participant Dropout Same Nicotine Content Group	19 Participants	—
Predictors of Participant Dropout Age group 18-29	20 Participants	—
Predictors of Participant Dropout Age group 30-39	14 Participants	—
Predictors of Participant Dropout Age group 40-49	15 Participants	—
Predictors of Participant Dropout Age group 50-59	18 Participants	—
Predictors of Participant Dropout Age group 60-65	4 Participants	—
Predictors of Participant Dropout Not currently working	31 Participants	—
Predictors of Participant Dropout Currently working	40 Participants	—
Predictors of Participant Dropout BMI Underweight (<18.5)	6 Participants	—
Predictors of Participant Dropout BMI Normal weight (>=18.5 and <25)	17 Participants	—
Predictors of Participant Dropout BMI Overweight (>=25 and <30)	15 Participants	—
Predictors of Participant Dropout BMI Obese (>=30)	33 Participants	—

SECONDARY outcome

Timeframe: 18 weeks

Population: All randomized participants

Measured by self-reported cigarettes per day at in-person clinic visits using 6-day follow back

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Cigarettes Per Day	21.0 cigarettes per day Interval 19.2 to 22.8	25.1 cigarettes per day Interval 23.6 to 26.6

SECONDARY outcome

Timeframe: 18 weeks

Population: All randomized participants

Measured by cotinine (ng/ml) measured in plasma

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Nicotine Exposure	128.6 ng/ml Interval 101.9 to 155.2	265.3 ng/ml Interval 242.6 to 287.9

SECONDARY outcome

Timeframe: 18 weeks

Population: All randomized participants

Measured in carbon monoxide levels by expired CO

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Smoke Exposure	27.2 parts per million (ppm) Interval 24.4 to 30.0	31.2 parts per million (ppm) Interval 28.9 to 33.6

SECONDARY outcome

Timeframe: 18 weeks

Population: All randomized participants

Perceived Stress is measured via the Perceived Stress Scale Score. The 10-item version was used. Scale range is 0-40. Higher scores indicate more stress.

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=122 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Perceived Stress	12.9 score on a scale Interval 11.8 to 14.1	11.1 score on a scale Interval 10.2 to 12.11

SECONDARY outcome

Timeframe: 15 weeks

Population: A subset of participants was randomly selected to complete the cortisol collection procedure and those who provided usable samples 1-3 were used in this analysis

Salivary Cortisol Cortisol is produced by the hypothalamic-pituitary-adrenal axis (HPA) axis in response to stress. Peak cortisol measures during the cortisol awakening response were used.

Outcome measures

Outcome measures
Measure	Reduced Nicotine Content Cigarettes n=15 Participants The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=27 Participants The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Cortisol	0.32 ng/dl Interval -0.02 to 0.67	0.48 ng/dl Interval 0.29 to 0.68

Adverse Events

Reduced Nicotine Content Cigarettes

Serious events: 11 serious events

Other events: 54 other events

Deaths: 1 deaths

Same Nicotine Content Cigarettes

Serious events: 11 serious events

Other events: 63 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Reduced Nicotine Content Cigarettes n=122 participants at risk The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 participants at risk The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Musculoskeletal and connective tissue disorders Back pain	5.7% 7/122 • Number of events 7 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	4.9% 6/123 • Number of events 6 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Depression	5.7% 7/122 • Number of events 7 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	8.1% 10/123 • Number of events 10 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
General disorders Flu like symptoms	6.6% 8/122 • Number of events 9 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	3.3% 4/123 • Number of events 4 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Vascular disorders Hypertension	9.8% 12/122 • Number of events 12 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	8.1% 10/123 • Number of events 11 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic, and mediastinal disorders- Other	9.0% 11/122 • Number of events 11 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	10.6% 13/123 • Number of events 13 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Surgical and medical procedures Surgical and medical procedures - Other	7.4% 9/122 • Number of events 9 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	10.6% 13/123 • Number of events 14 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Upper respiratory infection	16.4% 20/122 • Number of events 26 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	17.1% 21/123 • Number of events 23 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	1.6% 2/122 • Number of events 2 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	6.5% 8/123 • Number of events 8 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.

Additional Information

Nicolle Krebs

Penn State College of Medicine

Phone: 717-531-5673

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Reduced Nicotine Content Cigarettes n=122 participants at risk The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette. Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette	Same Nicotine Content Cigarettes n=123 participants at risk The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette) Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette
Gastrointestinal disorders Abdominal pain	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Gastrointestinal disorders Anal fistula	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Appendicitis	1.6% 2/122 • Number of events 2 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Musculoskeletal and connective tissue disorders Back pain	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 2 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Cardiac disorders Chest pain - cardiac	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
General disorders Death	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Depression	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Injury, poisoning and procedural complications Fall	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
General disorders Flu like symptoms	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Vascular disorders Hypertension	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
General disorders Pain	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Gastrointestinal disorders Pancreatitis	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Psychiatric disorders - Other	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Reproductive system and breast disorders Reproductive system and breast disorders - Other	0.00% 0/122 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Suicidal ideation	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Surgical and medical procedures Surgical and medical procedures - Other	1.6% 2/122 • Number of events 2 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Vascular disorders Thromboembolic event	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.81% 1/123 • Number of events 3 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Nervous system disorders Transient ischemic attacks	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Wheezing	0.82% 1/122 • Number of events 1 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/123 • 33 weeks Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.