Bosentan for Poorly Controlled Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: bosentan; placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Bosentan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Asthma

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.
    

Eligibility 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.