Bosentan for Poorly Controlled Asthma

• ClinicalTrials.gov Identifier: NCT00815347
• Recruitment Status: Terminated
• First Posted: December 30, 2008
• Results First Posted: October 1, 2012
• Last Update Posted: October 1, 2012
• Sponsor: UConn Health
• Collaborator: Actelion
• Information provided by (Responsible Party): Mark Metersky, UConn Health

Study Description

Brief Summary:

Hypothesis: The endothelin-1 receptor antagonist, bosentan when added to the treatment of asthma patients who are symptomatic despite the use of controller therapy will improve asthma symptoms and physiology.

Twenty patients with a diagnosis of asthma, between the ages of 21 and 70 who are symptomatic despite the use of at least one controller medication will be randomized to either placebo or active medication for an 8 week period (initial 4 weeks is at 1/2 of final dose as per package insert and FDA approval). Measures of lung function and symptoms will be recorded. Patients will then cross over, so that patients initially on placebo will receive active drug for 8 weeks and those initially on active drug will receive placebo. The same endpoints will be measured. The acute bronchodilator effects of the drug will also be tested on the first day of therapy at the full therapeutic dose.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: bosentan; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of the ET-1 Receptor Antagonist, Bosentan on Patients With Poorly Controlled Asthma-A 17 Week, Double-blind, Placebo Controlled Crossover Trial
• Study Start Date: December 2008
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm

Intervention/treatment

1 Crossover

Drug: bosentan; Bosentan 62.5mg or placebo orally, twice a day for four weeks. After four weeks at this dose the subjects will have an increase to bosentan 125 mg or placebo orally twice daily for another four weeks. At week eight, subjects will crossover to bosentan or placebo depending upon their first randomization.; Drug: placebo; Bosentan 62.5mg or placebo orally, twice a day for four weeks. After four weeks at this dose the subjects will have an increase to bosentan 125 mg or placebo orally twice daily for another four weeks. At week eight, subjects will crossover to bosentan or placebo depending upon their first randomization.

Outcome Measures

Primary Outcome Measures :

1. Change in FEV1 [ Time Frame: 1, 2, 4 hours after dosing ]
2. Peak Flow [ Time Frame: last 7 days of each dosing period ]
3. Symptom Scores [ Time Frame: Last 7 days of each dosing period ]
   Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)

Secondary Outcome Measures :

1. FEV1 [ Time Frame: end of dosing period ]
2. Rescue Beta-agonist [ Time Frame: end of each dosing period ]
3. Asthma Control Test Questionnaire [ Time Frame: end of each dosing period ]
   Patient reported outcome minimum 5 (no symptoms) maximum 25 (severe symptoms)

Other Outcome Measures:

1. Requirement for Escalation of Controller Medication. [ Time Frame: 17 weeks ]
2. Requirement for Urgent Medical Care for Asthma. [ Time Frame: 17 weeks ]
3. Ability to Taper Systemic Steroids Among Those Patients Who Are on Systemic Steroids at Study Entry. [ Time Frame: 17 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of asthma, maintained on a minimum of 1 anti-inflammatory/controller and daily long acting B-agonist therapy with inadequate control of symptoms. (Defined as symptoms including wheezing, chest tightness or shortness of breath occurring at least 3 times a week or requiring use of "rescue" short-acting B-agonist at least 3 times a week).
• FEV1 less than 80% of predicted and greater than 40% at screening visit.
• A minimum of 12% reversibility of FEV1 after albuterol on screening visit or previously documented during the prior two years.
• Women of childbearing potential must use 2 non-hormonal methods of birth control (2 methods between the subject and her partner) while on the study and for 1 month after the last dose of study medication.
• Male subjects must use two non hormonal methods of birth control (2 methods between the subject and his partner) while on the study and for 1 month after the last dose of study medication.

Exclusion Criteria:

• History of liver disease, clinically significant cardiac disease, renal disease or pulmonary disease other than asthma. Patients with clinically significant laboratory abnormalities of LFTs/bilirubin (AST/ALT, TBili, alkaline phosphatase) and clinically significant anemia will be excluded. Clinically significant anemia will be defined as any anemia resulting in serum Hgb more than 1 gm/dl below the LLN, Patients with isolated minimal elevations of bilirubin (eg. as occurs in Gilbert's disease) or minimal elevations in transaminases (less than 1.2 x ULN) without a history of liver disease, risk factors for liver disease or symptoms of liver disease may still be included in the study at the investigator's discretion, but will have LFT testing at each study visit.)
• Cigarette history of >10 pack years.
• Predicted inability to adhere to medication regimen or documentation requirements of the study (symptom and medication diaries).
• Respiratory infection during 30 days preceding screening visit.
• Requirement for change in scheduled asthma medication use, including oral steroid dose change, or acute medical care for asthma during the 30 days preceding screening visit.
• Predicted inability to safely refrain from B-agonist use for the required amount of time on study visit days.
• Use of tiotropium
• Pregnancy, breast feeding or the use of hormonal methods of birth control as the only means of birth control during the study.
• Use of potent CYP3A4 and CYP2C9 inhibitors, including, but not limited to azole antifungals, amiodarone, glyburide, warfarin, cyclosporine, ritonavir, other medications potentially toxic to the liver or bone marrow.
• Use of any illegal drugs or alcohol abuse.

Contacts and Locations

Locations

United States, Connecticut

University of Connecticut Health Center

Farmington, Connecticut, United States, 06030-2810

Sponsors and Collaborators

UConn Health

Actelion

Investigators

• Principal Investigator: Mark L Metersky, MD; UConn Health

More Information

• Responsible Party: Mark Metersky, MD, UConn Health
• ClinicalTrials.gov Identifier: NCT00815347
• Other Study ID Numbers: 08-287-1; 001
• First Posted: December 30, 2008
• Results First Posted: October 1, 2012
• Last Update Posted: October 1, 2012
• Last Verified: September 2012

Keywords provided by Mark Metersky, UConn Health:

Asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Bosentan; Antihypertensive Agents; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action