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

• Sponsor: Invion, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01825122
• Collaborator: (none)
• Enrollment: 155
• Locations: 4
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 38.8
• Patients Per Site Per Month: 2.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Smoking Cessation	Drug: Nadolol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Average Number of Cigarettes Smoked Per Day [Baseline to end of treatment, up to 15 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hope Research Center	Phoenix	Arizona	United States
2	Nuren Medical	Miami	Florida	United States	33144
3	Abel Buchheim Pharmaceutical Research	Miami	Florida	United States	33165
4	Washington University School of Medicine	St. Louis	Missouri	United States	63110

Sponsors and Collaborators

• Invion, Inc.

Investigators

• Principal Investigator: Mario Castro, M.D., Washington University of St. Louis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Invion, Inc.
• ClinicalTrials.gov Identifier: NCT01825122
• Other Study ID Numbers: INVSC001
• First Posted: Apr 5, 2013
• Last Update Posted: Feb 1, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Nadolol

Study Results

Participant Flow

Arm/Group Title	Placebo	Active, Nadolol
Arm/Group Description	placebo Placebo	Active Nadolol
Period Title: Overall Study
STARTED	77	78
COMPLETED	67	59
NOT COMPLETED	10	19

Baseline Characteristics

Arm/Group Title	Placebo	Active, Nadolol	Total
Arm/Group Description	placebo Placebo	Active Nadolol	Total of all reporting groups
Overall Participants	77	78	155
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	67 87%	76 97.4%	143 92.3%
>=65 years	10 13%	2 2.6%	12 7.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.08 (13.58)	44.08 (12.52)	46.06 (13.17)
Gender (Count of Participants)
Female	45 58.4%	33 42.3%	78 50.3%
Male	32 41.6%	45 57.7%	77 49.7%
Region of Enrollment (participants) [Number]
United States	77 100%	78 100%	155 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population reflects all patients who achieved maintenance dosing, including those who did not complete the study

Arm/Group Title	Placebo	Active, Nadolol
Arm/Group Description	placebo Placebo	Active Nadolol
Measure Participants	72	73
≥ 70% Reduction from Baseline	36 46.8%	45 57.7%
< 70% reduction from baseline	36 46.8%	28 35.9%

Adverse Events

Time Frame	Up to 30 days following discontinuation of the study, for up to 21 weeks
Arm/Group Title	Placebo		Active, Nadolol
Arm/Group Description	placebo Placebo		Active Nadolol
All Cause Mortality
	Placebo		Active, Nadolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Active, Nadolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/77 (1.3%)		2/78 (2.6%)
Musculoskeletal and connective tissue disorders
Back pain	0/77 (0%)	0	1/78 (1.3%)	1
Psychiatric disorders
Bipolar episode	0/77 (0%)	0	1/78 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	1/77 (1.3%)	1	0/78 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Active, Nadolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/77 (44.2%)		35/78 (44.9%)
Cardiac disorders
Dizziness	5/77 (6.5%)		3/78 (3.8%)
Gastrointestinal disorders
Abdominal pain upper	4/77 (5.2%)		2/78 (2.6%)
Diarrhoea	3/77 (3.9%)		7/78 (9%)
Dry mouth	17/77 (22.1%)		21/78 (26.9%)
Dysgeusia	8/77 (10.4%)		6/78 (7.7%)
Nausea	1/77 (1.3%)		4/78 (5.1%)
Nervous system disorders
Headache	6/77 (7.8%)		3/78 (3.8%)

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.