Smoking Cessation
Conditions
Brief summary
To test the hypothesis that treatment with the inverse agonist nadolol will improve smoking cessation in patients with chronic cough associated with long-term smoking, with or without airflow obstruction, including those with established chronic obstructive pulmonary disease (COPD) (chronic bronchitis dominant) or non-obstructive chronic bronchitis (NCB), compared to placebo and standard of care, while undergoing a validated smoking cessation program.
Interventions
DRUGNadolol
DRUGPlacebo
Sponsors
Invion, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Potential study participants will be referred from approved smoking cessation programs or be willing to enter a smoking cessation program administered by the participating sites. Individuals who meet all of the following criteria at Visit 1 are eligible for enrollment as study participants: 1. Active cigarette-smoking males and females between the ages of 18-70 with chronic cough associated with long-term smoking, with or without airflow obstruction, including Non-obstructive chronic bronchitis (NCB) or physician-diagnosed COPD (chronic bronchitis dominant), as defined by the American Thoracic Society. 2. Committed desire to quit smoking in conjunction with participation in an approved smoking cessation program administered by the participating sites. Enrollment in the smoking cessation program must take place prior to Visit 3 (third dose escalation visit). 3. Diagnosis of COPD (chronic bronchitis dominant) or NCB, or presenting with chronic cough associated with long-term smoking. 4. Pre-bronchodilator FEV1 greater than 55% of predicted 5. Baseline blood pressure ≥ 110/65mm Hg 6. Baseline heart rate ≥ 60 beats/min. 7. Smoking at least 10 cigarettes per day prior to participation in the approved smoking cessation program. 8. Self-reported prior failure(s) to quit smoking during participation in a smoking cessation program. 9. Able to complete diary cards and comply with study procedures. 10. Females of childbearing age may participate only if they have a negative pregnancy test, are non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.
Exclusion criteria
Subjects who meet ANY of the following criteria are not eligible for enrollment: 1. Diagnosis of asthma, cystic fibrosis, or PiZZ emphysema 2. Inability or unwillingness to give written informed consent 3. History of upper/lower respiratory tract infection, COPD exacerbation requiring systemic steroids, antibiotics, and or ER visit or urgent care within 6 weeks of Visit 1 4. History of adverse reaction or allergy to nadolol 5. History of neurological, hepatic, renal, or other medical conditions that may interfere with the interpretation of data or the patient's participation in the study or may increase safety concerns 6. History of cardiovascular diseases including uncontrolled hypertension (BP \>160/100), ischemic heart disease, congestive heart failure (NYHA III or IV), valvular heart disease or cardiomyopathy 7. Known allergy or sensitivity to atropine or ipratropium bromide 8. Documented or self-reported current history of alcoholism or drug abuse 9. Participation in another research trial within 30 days of starting this trial 10. Unwillingness or inability to comply with study procedures 11. Inability to swallow the study medication 12. Pregnant or nursing 13. Current use of any OTC remedies containing pseudoephedrine, ephedrine-based or containing dietary or herbal supplements. 14. Scheduled for surgery requiring general anaesthesia 15. Referred for smoking cessation without serious commitment to quit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in the Average Number of Cigarettes Smoked Per Day | Baseline to end of treatment, up to 15 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo
Placebo | 77 |
| Active, Nadolol Active
Nadolol | 78 |
| Total | 155 |
Baseline characteristics
| Characteristic | Total | Placebo | Active, Nadolol |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 10 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 143 Participants | 67 Participants | 76 Participants |
| Age, Continuous | 46.06 years STANDARD_DEVIATION 13.17 | 48.08 years STANDARD_DEVIATION 13.58 | 44.08 years STANDARD_DEVIATION 12.52 |
| Gender Female | 78 Participants | 45 Participants | 33 Participants |
| Gender Male | 77 Participants | 32 Participants | 45 Participants |
| Region of Enrollment United States | 155 participants | 77 participants | 78 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 77 | 35 / 78 |
| serious Total, serious adverse events | 1 / 77 | 2 / 78 |
Outcome results
Primary
Change From Baseline in the Average Number of Cigarettes Smoked Per Day
Time frame: Baseline to end of treatment, up to 15 weeks
Population: The analysis population reflects all patients who achieved maintenance dosing, including those who did not complete the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline in the Average Number of Cigarettes Smoked Per Day | ≥ 70% Reduction from Baseline | 36 participants |
| Placebo | Change From Baseline in the Average Number of Cigarettes Smoked Per Day | < 70% reduction from baseline | 36 participants |
| Active, Nadolol | Change From Baseline in the Average Number of Cigarettes Smoked Per Day | ≥ 70% Reduction from Baseline | 45 participants |
| Active, Nadolol | Change From Baseline in the Average Number of Cigarettes Smoked Per Day | < 70% reduction from baseline | 28 participants |