Bosentan for Poorly Controlled Asthma

Asthma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00815347
• Other study ID #: 08-287-1
• Secondary ID: 001
• Status: Terminated
• Phase: Phase 2
• First received: December 29, 2008
• Last updated: September 28, 2012
• Start date: December 2008
• Est. completion date: September 2010

Study information

• Verified date: September 2012
• Source: University of Connecticut Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Connecticut Health Center	Farmington	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
University of Connecticut Health Center	Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Requirement for Escalation of Controller Medication.		17 weeks	No
Other	Requirement for Urgent Medical Care for Asthma.		17 weeks	No
Other	Ability to Taper Systemic Steroids Among Those Patients Who Are on Systemic Steroids at Study Entry.		17 weeks	No
Primary	Change in FEV1		1, 2, 4 hours after dosing	No
Primary	Peak Flow		last 7 days of each dosing period	No
Primary	Symptom Scores	Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)	Last 7 days of each dosing period	No
Secondary	FEV1		end of dosing period	No
Secondary	Rescue Beta-agonist		end of each dosing period	No
Secondary	Asthma Control Test Questionnaire	Patient reported outcome minimum 5 (no symptoms) maximum 25 (severe symptoms)	end of each dosing period	No