Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00511134
• Collaborator: Sunovion (Industry)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Objectives:

The primary objective of this study is to determine the efficacy of eszopiclone at treating sleep problems related to withdrawal from nicotine in healthy smokers attempting smoking cessation.

Sleep disturbances are a significant problem for smokers who are trying to quit smoking. Smokers may be more likely to have sleep problems and both nicotine withdrawal and agents used to aid smoking cessation (e.g., pharmacotherapies) may disrupt sleep. Lunesta (eszopiclone) is a medication that has been approved by the FDA to treat insomnia. Eszopiclone's efficacy for treating insomnia makes it a promising agent for treating nicotine withdrawal-related symptoms of sleep disturbance.

This study will be 7 weeks duration. All participants will begin taking Zyban at the beginning of week 1 and will be asked to try to quit smoking at the beginning of week 2. Participants will also begin to take Lunesta or matched placebo (3 mg qd x 6 weeks) on the target quit date at the beginning of week 2. All subjects will receive eight (8) weekly sessions of brief individual supportive smoking cessation counseling.

Hypothesis:

It is hypothesized that significantly fewer sleep problems will be reported by participants taking Lunesta as compared to placebo. Specifically, it is expected that participants taking Lunesta will report less difficulty falling and staying asleep, higher sleep quality, and less insomnia-related fatigue and distress than participants taking placebo.

Condition or Disease	Intervention/Treatment	Phase
Insomnia; Nicotine Dependence	Drug: Eszopiclone; Drug: Bupropion	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled, Randomized Trial of Eszopiclone for the Treatment of Bupropion- and Abstinence-Related Insomnia During Smoking Cessation
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zyban + Lunesta Zyban (150 mg qd x 7 days then 150 mg bid x 6 weeks) + Lunesta (3 mg qd x 6 weeks)	Drug: Eszopiclone; eszopiclone (lunesta) - 3 mg qd x 6 weeks, oral capsule; Other Names: Lunesta ; Drug: Bupropion; bupropion SR in oral capsule will be begun at the beginning of week 1 (150 mg qd x 7 days) with an increase to the full dose (150 mg bid x 6 weeks) at the beginning of week 2.; Other Names: Zyban
Placebo Comparator: Zyban + Placebo Zyban (150 mg qd x 7 days then 150 mg bid x 6 weeks) + placebo (1 pill per day x 6 weeks)	Drug: Bupropion; bupropion SR in oral capsule will be begun at the beginning of week 1 (150 mg qd x 7 days) with an increase to the full dose (150 mg bid x 6 weeks) at the beginning of week 2.; Other Names: Zyban

Outcome Measures

Primary Outcome Measures

1. Level of Insomnia as Measured by the Insomnia Severity Index [6 weeks after target smoking quit date]

   Insomnia Severity Index (ISI): 13-item self-report measure which examines symptoms of insomnia, consequences of insomnia, and subjective distress related to sleep problems. Subjects rate the symptoms and consequences of insomnia on a 5 point Likert scales. For example, subjects are asked to rate the severity of their insomnia (e.g., difficulty falling asleep from 0=none to 4=very severe). Scores on the first 7 items are summed for a total insomnia score ranging from 0-28.

Secondary Outcome Measures

1. Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level [6 weeks after target smoking quite date]

   Endpoint abstinence will be defined as 0 cigarettes over the seven days prior to the subject's Timeline Follow-Back evaluation at the end of week 7 (end of trial) and a Carbon Monoxide (CO) level ≤ 5.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Are between ages 18-65 years old.

• Meet DSM-IV criteria for nicotine dependence.

• Smoke at least 15 cigarettes (3/4 pack) daily (averaged over 1 week, in the past 1 month) and have an expired breath CO level > 10.

• At the time of initial evaluation, are motivated to quit smoking in the next 30 days.

• Receive a score of ≥ 10 on the Insomnia Severity Index (ISI)

• Have the capacity to give informed consent, and are English-speaking.

Exclusion Criteria:

• Are taking an over-the-counter or prescription medications that are known to affect sleep.

• Are taking medications contraindicated for use with eszopiclone or bupropion including: Ketoconazole, Itraconazole, Clarithromycin, Erythromycin, Nefazodone, Troleandomycin, Ritonavir, Nelfinavir, Trazodone, and Methadone.

• Are using any over-the-counter analgesics that contain caffeine.

• Have serious medical disorders that may make participation in the trial unsafe.

• Are physiologically dependent on and/or abusing alcohol or other drugs of abuse (e.g., cocaine, opiates, benzodiazepines, etc.) in the past 6 months prior to randomization into the trial.

• Consume greater than 1 alcoholic beverage per day or greater than 7 alcoholic drinks per week.

• Meet DSM-IV criteria for a current diagnosis of major depressive disorder, panic disorder or post-traumatic stress disorder, or a current or past history bipolar disorder, schizophrenia, or anorexia or bulimia nervosa. Have a past history of major depression, with historical evidence of suicidal or homicidal behavior, or psychotic symptoms.

• Have the presence of suicidal or homicidal ideation, or significant impairment of social or occupational functioning, either at study baseline during the evaluation process, or during participation in the trial.

• Are from the same household as another study participant.

• A history of seizures of any etiology.

• A history of hypersensitivity to bupropion or Lunesta (eszopiclone).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Connecticut Mental Health Center	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University
• Sunovion

Investigators

• Principal Investigator: Andrea H. Weinberger, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00511134
• Other Study ID Numbers: 0609001866; ESRC099
• First Posted: Aug 3, 2007
• Last Update Posted: May 9, 2022
• Last Verified: May 1, 2022

• Keywords provided by Yale University: insomnia; nicotine dependence; smoking; smoking cessation; zyban
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Tobacco Use Disorder; Eszopiclone; Bupropion

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the Greater New Haven area and surrounding communities through targeted television, radio, and newspaper ads, fliers, and referrals from clinicians. Recruitment occurred between July of 2007 and October of 2008. Approximately 900 phone screens and 12 in-person screens were completed during the course of the study.
Pre-assignment Detail	Major reasons for exclusion at phone screen were report of no sleep problems, use of illegal substances, psychiatric or medical exclusions, and low smoking. Major reasons for exclusion during the in-person screening process included withdrawal of informed consent, alcohol or illicit drug use, and low smoking.

Arm/Group Title	Zyban + Lunesta	Zyban + Placebo
Arm/Group Description	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks)	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks)
Period Title: Overall Study
STARTED	1	3
COMPLETED	1	1
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Zyban + Lunesta	Zyban + Placebo	Total
Arm/Group Description	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks)	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks)	Total of all reporting groups
Overall Participants	1	3	4
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	3 100%	4 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	1 25%
Male	1 100%	2 66.7%	3 75%
Region of Enrollment (participants) [Number]
United States	1 100%	3 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Level of Insomnia as Measured by the Insomnia Severity Index
Description	Insomnia Severity Index (ISI): 13-item self-report measure which examines symptoms of insomnia, consequences of insomnia, and subjective distress related to sleep problems. Subjects rate the symptoms and consequences of insomnia on a 5 point Likert scales. For example, subjects are asked to rate the severity of their insomnia (e.g., difficulty falling asleep from 0=none to 4=very severe). Scores on the first 7 items are summed for a total insomnia score ranging from 0-28.
Time Frame	6 weeks after target smoking quit date

Outcome Measure Data

Analysis Population Description

Baseline descriptive data was examined for the 4 participants. Outcome measures were available for 2 participants. Due to the small number of participants, statistical comparisons were not able to be performed.

Arm/Group Title	Zyban + Lunesta	Zyban + Placebo
Arm/Group Description	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks)	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks)
Measure Participants	1	1
Median (Full Range) [Units on a Scale]	11 (0)	5 (0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zyban + Lunesta, Zyban + Placebo
	Comments	It was hypothesized that the Zyban+Lunesta group would report lower ISI scores at end of trial than the Zyban+Placebo group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Descriptive data
	Comments

2. Secondary Outcome

Title	Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level
Description	Endpoint abstinence will be defined as 0 cigarettes over the seven days prior to the subject's Timeline Follow-Back evaluation at the end of week 7 (end of trial) and a Carbon Monoxide (CO) level ≤ 5.
Time Frame	6 weeks after target smoking quite date

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zyban + Lunesta	Zyban + Placebo
Arm/Group Description	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks)	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks)
Measure Participants	1	3
Number [participants]	1 100%	1 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zyban + Lunesta, Zyban + Placebo
	Comments	It is predicted that subjects taking eszopiclone will be more likely to report abstinence at trial endpoint than those taking placebo.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Fisher Exact
	Comments	Degrees of freedom=1

Adverse Events

Time Frame	1 year, 3 months
Adverse Event Reporting Description	weekly questionnaire
Arm/Group Title	Zyban + Lunesta		Zyban + Placebo
Arm/Group Description	Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks)		Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks)
All Cause Mortality
	Zyban + Lunesta		Zyban + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zyban + Lunesta		Zyban + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Zyban + Lunesta		Zyban + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.