Evaluation of a Tailored Smoking Cessation Treatment Algo... | NCT00894166

Name	Class
Philip Morris USA, Inc.	INDUSTRY

Description Module

Brief Summary

Nicotine replacement therapy (NRT) is a well-tolerated and efficacious smoking cessation treatment, and yet many smokers fail to quit using NRT. Many of these smokers may benefit from prescription treatment alternatives, including Zyban or Chantix. In this study, the investigators propose to develop and evaluate a stepped-care treatment algorithm that would evaluate whether smokers who receive treatment with NRT should be supplemented with Zyban or switched to Chantix only based on: 1) their initial response to NRT; and 2) individual genetic factors found to predict smoking cessation in other studies evaluating these treatments. This study is a continuation of our previous studies showing that abstinence rates can be increased by starting nicotine patch therapy two weeks before the quit date. The investigators will provide pre-cessation NRT to all participants initially. Those who do not show a favorable response on early indicators of success (e.g., smoking in the first week after the target quit-smoking date) will receive "rescue" treatment by having their NRT treatment supplemented with Zyban , by being switched to treatment with Chantix or will remain on NRT (control).

The investigators hypothesize that "Rescue" treatment with Zyban in combination with NRT or Chantix will increase success rates over leaving subjects on NRT when they are NRT insufficient responders, i.e. they have shown an unfavorable response to NRT in the first week pre-quit or the first week post-quit.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Nicotine Replacement Therapy Responder	Active Comparator	Nicotine Responders	Drug: Nicotine Patches
Pre-Quit Rescue to Bupropion & Nicotine	Active Comparator	Participants not responsive to nicotine patches who are randomly assigned at week 2 to use of Zyban (bupropion) in combination with nicotine patches	Drug: Nicotine patches, then bupropion & nicotine patches (Pre-Quit)
Pre-Quit Rescue to Varenicline	Active Comparator	Participants not responsive to nicotine patches who are randomly assigned at week 2 to use of Chantix (varenicline)	Drug: Nicotine patches, then varenicline (Pre-Quit)
Pre-Quit Rescue to Nicotine	Active Comparator	Participants not responsive to nicotine patches who are randomly assigned at week 2 to continued use of nicotine patches	Drug: Nicotine patches, then nicotine patches (Pre-Quit)
Post-Quit Rescue to Bupropion & Nicotine	Active Comparator	Participants not responsive to nicotine patches who are randomly assigned at week 4 to use of Zyban (bupropion) in combination with nicotine patches

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Nicotine Patches	Drug	21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Measure	Description	Time Frame
Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment)	A self report of no cigarettes smoked confirmed by expired air carbon monoxide of <=10ppm was the criterion for abstinence.	weeks 8-11 after quit date

Measure	Description	Time Frame
Abstinence (7 Days) at 6 Months.		point abstinence (7 days) at 6 months post-quit date
Continuous Abstinence From Smoking at 6 Months Post Quit.		continuous abstinence at 6 months post quit day

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

18-65 years old
smoked an average of at least 10 cigarettes per day for three cumulative years of a brand that delivers (by Federal Trade Commission rated yields) at least 0.5mg nicotine
expired carbon monoxide reading of at least 15ppm
express a desire to quit smoking in the next 30 days

Exclusion Criteria:

Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
Hypotension (systolic <90 mm Hg, diastolic <60 mm Hg).
Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
Coronary heart disease;
Lifetime history of heart attack;
Cardiac rhythm disorder (irregular heart rhythm);
Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
History of skin allergy;
Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
Liver or kidney disorder (except kidney stones, gallstones);
Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
Active ulcers in the past 30 days;
Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
History of migraine headaches in the past 5 years;
History of fainting;
Problems giving blood samples;
Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
Other major medical condition;
Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and ADHD);
Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score >9 (or who score >0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment;
Bulimia or anorexia;
Pregnant or nursing mothers;
Use (within the past 30 days) of:
Illegal drugs (or if the urine drug screen is positive),
Experimental (investigational) drugs;
Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed)
Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;
Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse. Potential participants will be asked the first two questions on the AUDIT questionnaire during the phone screen. If the person scores "4" on both questions, a screening appointment will not be scheduled. During the screening session the entire AUDIT questionnaire will be administered. Females who score greater than or equal to 13 and males who score greater than or equal to 15 will be excluded from the study.
Significant adverse reaction to Wellbutrin / Zyban or Chantix / Varenicline in the past

Name	Affiliation	Role
Jed E Rose, Ph.D.	Duke University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Duke Center for Nicotine & Smoking Cessation Research		Charlotte, Durham, Raleigh, Winston-Salem	North Carolina		United States

PubMed Identifier	Type	Citation	Retractions
37230961	Derived	Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.
37142273	Derived	Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting. 21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting.
BG001	Pre-Quit Randomization to Bupropion + NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches.
BG002	Pre-Quit Randomization to Varenicline	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use varenicline.
BG003	Pre-Quit Randomization to NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment,who are randomly assigned at week 2 to use continued use of nicotine patches.
BG004	Post-Quit Randomization to Bupropion + NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use of bupropion in combination with nicotine patches.
BG005	Post-Quit Randomized to Varenicline	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use varenicline.
BG006	Post-Quit Randomized to NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use nicotine patches.
BG007	Withdrew Prior to Randomization	These subjects dropped from study participation after the first study session; therefore, they were never randomized into one of the study groups.
BG008	Total	Total of all reporting groups

Units	Counts
Participants	BG000132 BG001109 BG002112 BG003114 BG00434 BG00536 BG00635 BG00734 BG008606

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment)

A self report of no cigarettes smoked confirmed by expired air carbon monoxide of <=10ppm was the criterion for abstinence.

All participants were included in the analyses except those dropping out prior to randomization points, those censored for taking contraindicated medications or failing to meet other inclusion criteria, and one death having no apparent relationship to treatment.

Posted

Number

95% Confidence Interval

percentage of subjects abstinent

weeks 8-11 after quit date

ID	Title	Description
OG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting.
OG001	Pre-Quit Randomization to Bupropion + NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches.
OG002	Pre-Quit Randomization to Varenicline	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use varenicline.
OG003	Pre-Quit Randomization to NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment,who are randomly assigned at week 2 to use continued use of nicotine patches.
OG004	Post-Quit Randomization to Bupropion + NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use of bupropion in combination with nicotine patches.
OG005	Post-Quit Randomized to Varenicline	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use varenicline.
OG006	Post-Quit Randomized to NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use nicotine patches.

Units	Counts
Participants	OG000120 OG00199 OG002103 OG003

Title

Denominators

Categories

Title	Measurements
	OG00059.2(50.4 to 68) OG00128.3(19.4 to 37.2) OG00223.3(15.1 to 31.5) OG003

Secondary

Abstinence (7 Days) at 6 Months.

Posted

Number

percentage of subjects

point abstinence (7 days) at 6 months post-quit date

ID	Title	Description
OG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting. 21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
OG001	Pre-Quit Randomization to Bupropion + NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches. 21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Secondary

Continuous Abstinence From Smoking at 6 Months Post Quit.

Posted

Number

percentage of subjects

continuous abstinence at 6 months post quit day

ID	Title	Description
OG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting. 21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
OG001	Pre-Quit Randomization to Bupropion + NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches. 21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	NRT Responder	Participants in this group showed both a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting.	3	132	88	132
EG001	Pre-Quit Randomization to Bupropion + NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches.	4	109	74	109
EG002	Pre-Quit Randomization to Varenicline	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use varenicline.	3	112	64	112
EG003	Pre-Quit Randomization to NRT	Participants not showing a >50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment,who are randomly assigned at week 2 to use continued use of nicotine patches.	2	114	85	114
EG004	Post-Quit Randomization to Bupropion + NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use of bupropion in combination with nicotine patches.	2	34	31	34
EG005	Post-Quit Randomized to Varenicline	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use varenicline.	1	36	27	36
EG006	Post-Quit Randomized to NRT	Participants who did show >50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use nicotine patches.	1	35	28	35

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Chest Pain, shortness of breath, vision loss	General disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected109 at risk EG0020 events0 affected112 at risk EG0030 events0 affected114 at risk EG0040 events0 affected34 at risk EG0050 events0 affected36 at risk EG0060 events0 affected35 at risk
Hives, itching, knot in throat	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected109 at risk EG0020 events0 affected112 at risk EG003
Chest Pain, myocardial infarction	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
Chest Pain worsened with inspiration	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
psychiatric side effects	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0021 events1 affected112 at risk EG003
urticaria and shortness of breath	Immune system disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected109 at risk EG0020 events0 affected112 at risk EG003
paroxsymal supraventricular tachycardia and fainting	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected109 at risk EG0020 events0 affected112 at risk EG003
chest pain, new left bundle branch block	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
Chest pain, unifocal PVCs	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0021 events1 affected112 at risk EG003
Rash distant from patch site	Immune system disorders	Non-systematic Assessment	EG0001 events1 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
Hallucinations, chest pains, vomiting	General disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
Body aches, generalized weakness, sensation of throat swelling, lightheadedness,difficulty breathing	General disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0021 events1 affected112 at risk EG003
stroke and death	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003
myocardial infaction	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected132 at risk EG0010 events0 affected109 at risk EG0020 events0 affected112 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
HEADACHE	Nervous system disorders	Systematic Assessment	EG00023 events18 affected132 at risk EG00121 events17 affected109 at risk EG0029 events9 affected112 at risk EG00322 events17 affected114 at risk EG00411 events5 affected34 at risk EG0057 events6 affected36 at risk EG00611 events4 affected35 at risk
EXCESSIVE SWEATING	General disorders	Systematic Assessment	EG0008 events7 affected132 at risk EG00121 events12 affected109 at risk EG0025 events4 affected112 at risk EG003
SWELLING	General disorders	Systematic Assessment	EG0003 events3 affected132 at risk EG0011 events1 affected109 at risk EG0023 events3 affected112 at risk EG003
MOUTH/THROAT IRRITATION	General disorders	Systematic Assessment	EG00015 events11 affected132 at risk EG0019 events7 affected109 at risk EG0022 events2 affected112 at risk EG003
DRY MOUTH	General disorders	Systematic Assessment	EG00024 events14 affected132 at risk EG00143 events19 affected109 at risk EG00214 events7 affected112 at risk EG003
THIRST	General disorders	Systematic Assessment	EG00033 events19 affected132 at risk EG00141 events21 affected109 at risk EG00225 events12 affected112 at risk EG003
COUGHING	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00016 events10 affected132 at risk EG00121 events11 affected109 at risk EG00229 events15 affected112 at risk EG003
CHEST PAIN	General disorders	Systematic Assessment	EG0000 events0 affected132 at risk EG0011 events1 affected109 at risk EG0020 events0 affected112 at risk EG003
JOINT / MUSCLE PAIN	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00022 events14 affected132 at risk EG0016 events4 affected109 at risk EG0027 events4 affected112 at risk EG003
HEARTBURN	Gastrointestinal disorders	Systematic Assessment	EG00011 events9 affected132 at risk EG00118 events7 affected109 at risk EG0027 events4 affected112 at risk EG003
NAUSEA	Gastrointestinal disorders	Systematic Assessment	EG00011 events9 affected132 at risk EG0014 events4 affected109 at risk EG0025 events4 affected112 at risk EG003
CONSTIPATION	Gastrointestinal disorders	Systematic Assessment	EG00013 events7 affected132 at risk EG00116 events9 affected109 at risk EG0023 events3 affected112 at risk EG003
UPSET STOMACH	Gastrointestinal disorders	Systematic Assessment	EG0008 events8 affected132 at risk EG0013 events3 affected109 at risk EG0025 events3 affected112 at risk EG003
DIARRHEA	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected132 at risk EG0013 events2 affected109 at risk EG0027 events6 affected112 at risk EG003
IRRITABILITY	Nervous system disorders	Systematic Assessment	EG00035 events20 affected132 at risk EG00122 events16 affected109 at risk EG00231 events18 affected112 at risk EG003
NIGHTMARES	Nervous system disorders	Systematic Assessment	EG00011 events8 affected132 at risk EG0018 events5 affected109 at risk EG0028 events8 affected112 at risk EG003
VIVID DREAMS	Nervous system disorders	Systematic Assessment	EG00085 events36 affected132 at risk EG00174 events35 affected109 at risk EG00250 events25 affected112 at risk EG003
INSOMNIA	Nervous system disorders	Systematic Assessment	EG00033 events20 affected132 at risk EG00137 events26 affected109 at risk EG00217 events14 affected112 at risk EG003
DEPRESSION	Psychiatric disorders	Systematic Assessment	EG0006 events3 affected132 at risk EG0013 events3 affected109 at risk EG0028 events6 affected112 at risk EG003
ANXIETY	Psychiatric disorders	Systematic Assessment	EG00015 events14 affected132 at risk EG00126 events16 affected109 at risk EG00215 events8 affected112 at risk EG003
TREMOR	Nervous system disorders	Systematic Assessment	EG0001 events1 affected132 at risk EG0016 events5 affected109 at risk EG0021 events1 affected112 at risk EG003
DECREASED LIBIDO	Nervous system disorders	Systematic Assessment	EG0005 events5 affected132 at risk EG00110 events4 affected109 at risk EG00212 events6 affected112 at risk EG003
ITCHING/BURNING AT PATCH SITE	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00063 events27 affected132 at risk EG00128 events19 affected109 at risk EG00214 events13 affected112 at risk EG003
RASH AT PATCH SITE	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00030 events17 affected132 at risk EG0019 events8 affected109 at risk EG0027 events6 affected112 at risk EG003
RASH DISTANT FROM PATCH SITE	General disorders	Systematic Assessment	EG0006 events4 affected132 at risk EG0013 events3 affected109 at risk EG0022 events2 affected112 at risk EG003

ID	Term
D015438	Health Behavior
D001519	Behavior

ID	Term
D013812	Therapeutics
D011427	Propiophenones
D007659	Ketones
D009930	Organic Chemicals
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D011810	Quinoxalines

ID	Term
D061485	Tobacco Use Cessation Devices
D016642	Bupropion
D000068580	Varenicline