Efficacy of Naltrexone in Women's Smoking Cessation

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00271024
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 333
• Location: 1
• Arms: 4
• Duration (Months): 51
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

The purpose of the proposed study is to conduct a randomized, double-blind clinical trial to compare adjunct treatment with 50 mg oral naltrexone vs. placebo in conjunction with standard smoking cessation treatment with nicotine patch and counseling.

Hypotheses:

1. Naltrexone will improve smoking cessation quit rates, as measured at the end of active treatment (3 months) and during long term follow up (1 year).

2. Weight and smoking-related variables (i.e., less weight gain, as well as reduced craving and withdrawal) will be important factors by which naltrexone improves smoking cessation outcome.

3. These effects are predicted to be stronger in women compared to men.

Condition or Disease	Intervention/Treatment	Phase
Smoking; Smoking Cessation	Drug: Naltrexone (drug); Drug: Placebo (for Naltrexone)	Phase 2

Detailed Description

Although women may be particularly susceptible to the damaging effects of chronic cigarette smoking, evidence indicates that they may have more difficulty in maintaining smoking cessation than men. Given women's reduced response to nicotine replacement and other traditional treatments to habitual cigarette smoking, more targeted pharmacotherapy and intervention strategies may be necessary to improve their quit rates. Preliminary data by our group and others indicate that the opioid antagonist naltrexone may be an effective adjunctive pharmacotherapy approach for female smokers. The purpose of the proposed study is to conduct a randomized clinical trial to compare adjunct treatment with 50 mg oral naltrexone vs. placebo in conjunction with standard smoking cessation treatment with nicotine patch and counseling. Participants (N=324) will be randomized to receive either naltrexone or placebo starting one week prior to the quit date (25 mg for three days; 50 mg thereafter) and continue for 12 weeks after the quit date. The effects of naltrexone will be evaluated during the pre-quit date period, initial smoking cessation, relapse prevention, and at one year follow-up. It is hypothesized that sex will moderate the effects of naltrexone on outcome, with naltrexone improving prolonged abstinence quit rates in women but not in men. The secondary goal will be to elucidate the mechanism underlying women's treatment response to naltrexone. Weight (relative weight gain and weight concerns) and smoking-related variables (reduced cigarette pleasure, taste, craving and relief of negative withdrawal affect) may be important factors by which naltrexone improves quit rates in women. Medication compliance, psychosocial stress and levels of naltrexone's metabolite, 6-B-naltrexol, will also be examined. In sum, the proposed clinical trial will provide a comprehensive study of sex differences in response to adjunct treatment with naltrexone for smoking cessation. Given the public health concerns and significant health consequences of women's continued high rates of smoking, the proposed study may provide important information on a novel treatment strategy targeting the endogenous opioid system to selectively aid in women's smoking cessation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 333 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Naltrexone in Women's Smoking Cessation
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Male Naltrexone 50 mg Naltrexone tablet	Drug: Naltrexone (drug); 50 mg q.d. for 13 weeks
Experimental: Female Naltrexone Females receiving either naltrexone (50 mg)	Drug: Naltrexone (drug); 50 mg q.d. for 13 weeks
Placebo Comparator: Male Placebo Males receiving Placebo (sugar pill)	Drug: Placebo (for Naltrexone); Sugar pill manufactured to mimic Naltrexone tablet
Placebo Comparator: Female Placebo Females receiving placebo (sugar pill)	Drug: Placebo (for Naltrexone); Sugar pill manufactured to mimic Naltrexone tablet

Outcome Measures

Primary Outcome Measures

1. Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date [4 Weeks Following Smoking Quit Date (Study week 7)]

   Prolonged Abstinence at 4 weeks post quit date (Study Week 7). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period.

2. Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date [12 Weeks Following Smoking Quit Date (Study week 15)]

   Prolonged Abstinence at 12 weeks post quit date (Study Week 15). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period.

3. 7-Day Point Prevalence Smoking Abstinence: 4 Weeks Post Quit-Date [4 Weeks Following Smoking Quit Date (Study week 7)]

   7-Day Point Prevalence smoking abstinence at 4 weeks post quit date (Study Week 7). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.

4. 7-Day Point Prevalence Smoking Abstinence: 12 Weeks Post Quit-Date [12 Weeks Following Smoking Quit Date (Study week 15)]

   7-Day Point Prevalence smoking abstinence at 12 weeks post quit date (Study Week 15). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.

5. 7-Day Point Prevalence Smoking Abstinence: 26 Weeks Post Quit-Date [26 Weeks Following Smoking Quit Date (Study week 29)]

   7-Day Point Prevalence smoking abstinence at 29 weeks post quit date (Study Week 29). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.

6. 7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date [52 Weeks Following Smoking Quit Date (Study week 55)]

   7-Day Point Prevalence smoking abstinence at 52 weeks post quit date (Study Week 55). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.

Secondary Outcome Measures

1. Weight Change at End of Treatment (Smoking Abstinent Only) [Weight change at 12 weeks post smoking quit date (study week 15)]

   Weight change in lbs at 12 weeks post smoking quit date (study week 15) for only those reporting continued smoking abstinence at the end of treatment. All data are Mean(SEM) and represent positive change, unless otherwise noted. Smoking abstinent for this measure defined as no smoking even 1 puff of a cigarette since the smoking quit date (study week 3), allowing for a 1-week grace period.

2. Weight Change at End of Treatment (Regardless of Quit Status) [Weight change at 12 weeks post quit date (study week 15) from smoking quit date]

   Weight change at 12 weeks post quit date (study week 15) for the whole sample regardless of quit status. All data is Mean(SEM) and represents a positive change unless otherwise noted.

3. Opioid Antagonist Reported Side Effects: 1-Week Post Quit Date [1-Week Post Quit Date (Study Week 4)]

   Participants reporting side effects during the previous week by pill type and sex, 1-week following quit date (Study week 4). Participants rated side effects experienced by None, Mild, or Severe.

4. Opioid Antagonist Reported Side Effects: 4-Weeks Post Quit Date [4-Weeks Post Quit Date (Study Week 7)]

   Participants reporting side effects during the previous week by pill type and sex, 4-weeks following quit date (Study week 7). Participants rated side effects experienced by None, Mild, or Severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age 18-65, male or female

2. Cigarette smoker of at least 15 but no more than 40 cigarettes daily for at least two years

3. Current diagnosis of DSM-IV Nicotine Dependence, based on SCID interview

4. Relatively healthy, with no medical or psychiatric conditions that would adversely interact with study parameters (see exclusion criteria for specific details)

5. Desire to quit smoking (self-report rating of interest in quitting at least a 7 on a 10-point scale)

6. Nicometer® cotinine level at baseline at least a 5 on a 6-point scale

7. Reports not quitting smoking in the past three months for more than one week duration

8. Agrees to attend behavioral counseling sessions and complete study measures

9. Has stable residence and telephone and can provide the name of an outside household collateral family member or close friend

Exclusion Criteria:

1. Substance Dependence in the last one year (other than DSM-IV Nicotine Dependence) or any history of Opioid Dependence (lifetime)

2. Major psychiatric disorder in the last one year, including Axis I disorders or any history of moderate/severe Axis II Disorder, Bipolar Disorder or Psychotic Disorder, based on SCID interview and standard cut-off thresholds on screening questionnaires

3. Past or current medical disorders (cardiovascular, hepatic, neurological, endocrine, etc.) which may adversely interact with study measures

4. Clinically significant lab test abnormalities, positive urine toxicology, or positive pregnancy test

5. Currently pregnant, plans to become pregnant, or lack of effective birth control over next three months, and/or currently lactating, or plans for breastfeeding over next three months

6. History of adverse reaction to opioid antagonist or nicotine replacement treatment

7. Use of any medication that may adversely interact with study measures (antidepressants, phenothiazines, benzodiazepines, etc.); recent or regular use of an opioid medication

8. Unwillingness to attend smoking cessation treatment sessions, take the nicotine patch, or be randomized into medication or placebo conditions, or be available for follow-up assessments

9. Unwillingness to agree to DNA analysis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago, Department of Psychiatry	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• National Institutes of Health (NIH)
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Andrea C King, PhD, The University of Chicago, Department of Psychiatry

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Main Study Website

Publications

• Epstein AM, King AC. Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav. 2004 Jan;77(1):29-37.
• King A, de Wit H, Riley RC, Cao D, Niaura R, Hatsukami D. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Nicotine Tob Res. 2006 Oct;8(5):671-82.
• King AC, Meyer PJ. Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Pharmacol Biochem Behav. 2000 Jul;66(3):563-72.
• King AC. Role of naltrexone in initial smoking cessation: preliminary findings. Alcohol Clin Exp Res. 2002 Dec;26(12):1942-4.

• Responsible Party: Andrea King, Associate Professor, University of Chicago
• ClinicalTrials.gov Identifier: NCT00271024
• Other Study ID Numbers: 13976A (R01 DA016834); R01DA016834
• First Posted: Dec 29, 2005
• Last Update Posted: Apr 26, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Andrea King, Associate Professor, University of Chicago: Smoking; Smoking Cessation
• Additional relevant MeSH terms: Naltrexone

Study Results

Participant Flow

Recruitment Details	Enrollment for this study lasted from August 2006-March 2009 with study visits taking place in 3 sites (The University of Chicago, Howard Brown Health Clinic, and the Respiratory Health Association). Follow-up interviews for the study concluded in April 2010.
Pre-assignment Detail	N=707 screened for participation (320 met exclusion criteria, 54/387 who passed chose not to participate) 333 participants were randomized into the trial

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Period Title: Overall Study
STARTED	80	77	88	88
Received Study Treatment	76	71	85	83
COMPLETED	58	51	65	64
NOT COMPLETED	22	26	23	24

Baseline Characteristics

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE	Total
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial	Total of all reporting groups
Overall Participants	80	77	88	88	333
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	80 100%	77 100%	86 97.7%	88 100%	331 99.4%
>=65 years	0 0%	0 0%	2 2.3%	0 0%	2 0.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.45 (10.97)	40.21 (10.98)	44.34 (11.49)	44.95 (10.45)	42.13 (11.27)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	88 100%	88 100%	176 52.9%
Male	80 100%	77 100%	0 0%	0 0%	157 47.1%
Region of Enrollment (participants) [Number]
United States	80 100%	77 100%	88 100%	88 100%	333 100%

Outcome Measures

1. Primary Outcome

Title	Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date
Description	Prolonged Abstinence at 4 weeks post quit date (Study Week 7). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period.
Time Frame	4 Weeks Following Smoking Quit Date (Study week 7)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	43 53.8%	29 37.7%	40 45.5%	39 44.3%

2. Secondary Outcome

Title	Weight Change at End of Treatment (Smoking Abstinent Only)
Description	Weight change in lbs at 12 weeks post smoking quit date (study week 15) for only those reporting continued smoking abstinence at the end of treatment. All data are Mean(SEM) and represent positive change, unless otherwise noted. Smoking abstinent for this measure defined as no smoking even 1 puff of a cigarette since the smoking quit date (study week 3), allowing for a 1-week grace period.
Time Frame	Weight change at 12 weeks post smoking quit date (study week 15)

Outcome Measure Data

Analysis Population Description

All participants completing through smoking quit date (study week 3) and who were smoking abstinent at end of treatment (study week 15)

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	23	12	17	23
Mean (Standard Error) [Pounds]	4.79 (0.78)	5.58 (0.78)	2.26 (0.68)	5.08 (0.69)

3. Primary Outcome

Title	Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date
Description	Prolonged Abstinence at 12 weeks post quit date (Study Week 15). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period.
Time Frame	12 Weeks Following Smoking Quit Date (Study week 15)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	23 28.8%	12 15.6%	17 19.3%	23 26.1%

4. Primary Outcome

Title	7-Day Point Prevalence Smoking Abstinence: 4 Weeks Post Quit-Date
Description	7-Day Point Prevalence smoking abstinence at 4 weeks post quit date (Study Week 7). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.
Time Frame	4 Weeks Following Smoking Quit Date (Study week 7)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	47 58.8%	33 42.9%	49 55.7%	43 48.9%

5. Secondary Outcome

Title	Weight Change at End of Treatment (Regardless of Quit Status)
Description	Weight change at 12 weeks post quit date (study week 15) for the whole sample regardless of quit status. All data is Mean(SEM) and represents a positive change unless otherwise noted.
Time Frame	Weight change at 12 weeks post quit date (study week 15) from smoking quit date

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome, regardless of their abstinence status at 12 weeks post quit date (study week 15)

Arm/Group Title	Placebo	Naltrexone
Arm/Group Description	Participants receiving Placebo as part of the trial	Participants receiving Naltrexone as part of the trial
Measure Participants	154	161
Mean (Standard Error) [Pounds]	5.29 (0.52)	3.42 (0.53)

6. Primary Outcome

Title	7-Day Point Prevalence Smoking Abstinence: 12 Weeks Post Quit-Date
Description	7-Day Point Prevalence smoking abstinence at 12 weeks post quit date (Study Week 15). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.
Time Frame	12 Weeks Following Smoking Quit Date (Study week 15)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	31 38.8%	24 31.2%	30 34.1%	31 35.2%

7. Primary Outcome

Title	7-Day Point Prevalence Smoking Abstinence: 26 Weeks Post Quit-Date
Description	7-Day Point Prevalence smoking abstinence at 29 weeks post quit date (Study Week 29). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.
Time Frame	26 Weeks Following Smoking Quit Date (Study week 29)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	22 27.5%	18 23.4%	20 22.7%	22 25%

8. Primary Outcome

Title	7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date
Description	7-Day Point Prevalence smoking abstinence at 52 weeks post quit date (Study Week 55). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame.
Time Frame	52 Weeks Following Smoking Quit Date (Study week 55)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3)were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Number [Participants]	14 17.5%	15 19.5%	14 15.9%	20 22.7%

9. Secondary Outcome

Title	Opioid Antagonist Reported Side Effects: 1-Week Post Quit Date
Description	Participants reporting side effects during the previous week by pill type and sex, 1-week following quit date (Study week 4). Participants rated side effects experienced by None, Mild, or Severe.
Time Frame	1-Week Post Quit Date (Study Week 4)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3) were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Nausea - "Mild"	16 20%	5 6.5%	24 27.3%	13 14.8%
Nausea - "Severe"	4 5%	3 3.9%	4 4.5%	2 2.3%
Vomiting - "Mild"	3 3.8%	0 0%	3 3.4%	5 5.7%
Vomiting - "Severe"	1 1.3%	0 0%	2 2.3%	0 0%
Headache- "Mild"	28 35%	17 22.1%	31 35.2%	33 37.5%
Headache - "Severe"	4 5%	2 2.6%	0 0%	2 2.3%
Light Headed/Dizzy - "Mild"	22 27.5%	16 20.8%	25 28.4%	17 19.3%
Light Headed/Dizzy - "Severe"	5 6.3%	1 1.3%	1 1.1%	0 0%
Flushed/Warm - "Mild"	12 15%	9 11.7%	24 27.3%	15 17%
Flushed/Warm - "Severe"	1 1.3%	1 1.3%	6 6.8%	6 6.8%
Tiredness - "Mild"	42 52.5%	34 44.2%	38 43.2%	33 37.5%
Tiredness - "Severe"	5 6.3%	7 9.1%	10 11.4%	9 10.2%
Anxiety/Agitation - "Mild"	33 41.3%	35 45.5%	31 35.2%	32 36.4%
Anxiety/Agitation - "Severe"	3 3.8%	3 3.9%	3 3.4%	6 6.8%
Increased Sexual Desire - "Mild"	10 12.5%	22 28.6%	9 10.2%	6 6.8%
Increased Sexual Desire - "Severe"	2 2.5%	6 7.8%	1 1.1%	0 0%
Insomnia - "Mild"	13 16.3%	16 20.8%	19 21.6%	12 13.6%
Insomnia - "Severe"	2 2.5%	3 3.9%	5 5.7%	3 3.4%
Constipation - "Mild"	18 22.5%	20 26%	24 27.3%	14 15.9%
Constipation - "Severe"	1 1.3%	1 1.3%	1 1.1%	3 3.4%
Diarrhea - "Mild"	6 7.5%	6 7.8%	5 5.7%	7 8%
Diarrhea - "Severe"	2 2.5%	0 0%	0 0%	1 1.1%
Joint or Muscle Pain - "Mild"	21 26.3%	21 27.3%	14 15.9%	13 14.8%
Joint or Muscle Pain - "Severe"	0 0%	2 2.6%	2 2.3%	5 5.7%

10. Secondary Outcome

Title	Opioid Antagonist Reported Side Effects: 4-Weeks Post Quit Date
Description	Participants reporting side effects during the previous week by pill type and sex, 4-weeks following quit date (Study week 7). Participants rated side effects experienced by None, Mild, or Severe.
Time Frame	4-Weeks Post Quit Date (Study Week 7)

Outcome Measure Data

Analysis Population Description

All participants who received study treatment by participating through smoking quit date (Study Week 3) were analyzed for this outcome.

Arm/Group Title	Naltrexone - MALE	Placebo - MALE	Naltrexone - FEMALE	Placebo - FEMALE
Arm/Group Description	Males receiving naltrexone as part of the trial	Males receiving placebo as part of the trial	Females receiving naltrexone as part of the trial	Females receiving placebo as part of the trial
Measure Participants	76	71	85	83
Nausea - "Mild"	3 3.8%	3 3.9%	12 13.6%	7 8%
Nausea - "Severe"	3 3.8%	1 1.3%	0 0%	0 0%
Vomiting - "Mild"	1 1.3%	0 0%	1 1.1%	0 0%
Vomiting - "Severe"	0 0%	0 0%	0 0%	0 0%
Headache- "Mild"	18 22.5%	23 29.9%	19 21.6%	19 21.6%
Headache - "Severe"	3 3.8%	1 1.3%	2 2.3%	1 1.1%
Light Headed/Dizzy - "Mild"	11 13.8%	7 9.1%	17 19.3%	14 15.9%
Light Headed/Dizzy - "Severe"	2 2.5%	0 0%	1 1.1%	0 0%
Flushed/Warm - "Mild"	6 7.5%	5 6.5%	22 25%	14 15.9%
Flushed/Warm - "Severe"	0 0%	2 2.6%	3 3.4%	1 1.1%
Tiredness - "Mild"	27 33.8%	27 35.1%	32 36.4%	24 27.3%
Tiredness - "Severe"	2 2.5%	2 2.6%	7 8%	7 8%
Anxiety/Agitation - "Mild"	18 22.5%	19 24.7%	27 30.7%	23 26.1%
Anxiety/Agitation - "Severe"	2 2.5%	3 3.9%	4 4.5%	3 3.4%
Increased Sexual Desire - "Mild"	25 31.3%	17 22.1%	11 12.5%	7 8%
Increased Sexual Desire - "Severe"	2 2.5%	4 5.2%	1 1.1%	2 2.3%
Insomnia - "Mild"	10 12.5%	13 16.9%	17 19.3%	10 11.4%
Insomnia - "Severe"	1 1.3%	1 1.3%	1 1.1%	2 2.3%
Constipation - "Mild"	13 16.3%	8 10.4%	18 20.5%	10 11.4%
Constipation - "Severe"	2 2.5%	2 2.6%	2 2.3%	1 1.1%
Diarrhea - "Mild"	7 8.8%	11 14.3%	6 6.8%	4 4.5%
Diarrhea - "Severe"	2 2.5%	0 0%	0 0%	1 1.1%
Joint or Muscle Pain - "Mild"	17 21.3%	15 19.5%	15 17%	16 18.2%
Joint or Muscle Pain - "Severe"	2 2.5%	2 2.6%	1 1.1%	1 1.1%

Adverse Events

Adverse Event Reporting Description	Number of participant at risk represent those assigned to either Naltrexone or Placebo condition (i.e. receiving treatment) - Placebo: n=154, Naltrexone: n=161
Arm/Group Title	Placebo		Naltrexone
Arm/Group Description	Participants receiving Placebo as part of the trial		Participants receiving Naltrexone as part of the trial
All Cause Mortality
	Placebo		Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/154 (1.3%)		2/161 (1.2%)
General disorders
Motor Vehicle Collision	1/154 (0.6%)	1	0/161 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Brain Mass	0/154 (0%)	0	1/161 (0.6%)	1
Lung Cancer	1/154 (0.6%)	1	0/161 (0%)	0
Psychiatric disorders
Suicidal Ideation Remitting in 2 Days with Recurrence	0/154 (0%)	0	1/161 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/154 (59.7%)		101/161 (62.7%)
General disorders
Nausea	26/154 (16.9%)		52/161 (32.3%)
Vomiting	5/154 (3.2%)		10/161 (6.2%)
Headache	57/154 (37%)		67/161 (41.6%)
Lightheaded or dizzy	37/154 (24%)		57/161 (35.4%)
Flushed or warm	36/154 (23.4%)		46/161 (28.6%)
Tiredness	91/154 (59.1%)		98/161 (60.9%)
Agitation or anxiety	82/154 (53.2%)		76/161 (47.2%)
Increased Sexual Desire	37/154 (24%)		45/161 (28%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.