Bosentan for Poorly Controlled Asthma

This study has been terminated.
(Difficulty in recruitment.)
Sponsor:
Collaborator:
Actelion
Information provided by (Responsible Party):
Mark Metersky, University of Connecticut Health Center
ClinicalTrials.gov Identifier:
NCT00815347
First received: December 29, 2008
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Asthma
Drug: bosentan
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Connecticut Health Center:

Primary Outcome Measures:
  • Change in FEV1 [ Time Frame: 1, 2, 4 hours after dosing ] [ Designated as safety issue: No ]
  • Peak Flow [ Time Frame: last 7 days of each dosing period ] [ Designated as safety issue: No ]
  • Symptom Scores [ Time Frame: Last 7 days of each dosing period ] [ Designated as safety issue: No ]
    Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)


Secondary Outcome Measures:
  • FEV1 [ Time Frame: end of dosing period ] [ Designated as safety issue: No ]
  • Rescue Beta-agonist [ Time Frame: end of each dosing period ] [ Designated as safety issue: No ]
  • Asthma Control Test Questionnaire [ Time Frame: end of each dosing period ] [ Designated as safety issue: No ]
    Patient reported outcome minimum 5 (no symptoms) maximum 25 (severe symptoms)


Other Outcome Measures:
  • Requirement for Escalation of Controller Medication. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • Requirement for Urgent Medical Care for Asthma. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • Ability to Taper Systemic Steroids Among Those Patients Who Are on Systemic Steroids at Study Entry. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: December 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815347

Locations
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030-2810
Sponsors and Collaborators
University of Connecticut Health Center
Actelion
Investigators
Principal Investigator: Mark L Metersky, MD University of Connecticut Health Center
  More Information

No publications provided

Responsible Party: Mark Metersky, MD, University of Connecticut Health Center
ClinicalTrials.gov Identifier: NCT00815347     History of Changes
Other Study ID Numbers: 08-287-1, 001
Study First Received: December 29, 2008
Results First Received: June 16, 2012
Last Updated: September 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Connecticut Health Center:
Asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014