Efficacy and Safety of Βeta-adrenoceptor Inverse Agonist and Biased Ligand, Nadolol, In Smoking Cessation of Patients With Chronic Cough With or Without Airflow Obstruction

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Placebo; Drug: Nadolol

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Hope Research Center
  • Florida
    • Miami, Florida, United States, 33165
      • Abel Buchheim Pharmaceutical Research
    • Miami, Florida, United States, 33144
      • Nuren Medical
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo
Experimental: Active, nadolol; Active	Drug: Nadolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in the Average Number of Cigarettes Smoked Per Day	Baseline to end of treatment, up to 15 weeks

Collaborators and Investigators

• Sponsor: Invion, Inc.
• Investigators: Principal Investigator: Mario Castro, M.D., Washington University of St. Louis

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: April 2, 2013
• First Submitted That Met QC Criteria: April 2, 2013
• First Posted (Estimate): April 5, 2013

Study Record Updates

• Last Update Posted (Estimate): February 1, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Nadolol
• Other Study ID Numbers: INVSC001