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Bosentan for Poorly Controlled Asthma

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

Tracking Information
First Submitted Date  ICMJE December 29, 2008
First Posted Date  ICMJE December 30, 2008
Results First Submitted Date  ICMJE June 16, 2012
Results First Posted Date  ICMJE October 1, 2012
Last Update Posted Date October 1, 2012
Study Start Date  ICMJE December 2008
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2012)
  • Change in FEV1 [ Time Frame: 1, 2, 4 hours after dosing ]
  • Peak Flow [ Time Frame: last 7 days of each dosing period ]
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: December 29, 2008)
  • Symptom scores during last 7 days of 125 mg dosing period of drug vs placebo (means with comparisons between drug and placebo scores for each patient and between baseline and drug). [ Time Frame: 17 weeks ]
  • Peak flow measurements during last 7 days of each 125 mg dosing period. [ Time Frame: 17 weeks ]
Change History Complete list of historical versions of study NCT00815347 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2012)
  • FEV1 [ Time Frame: end of dosing period ]
  • Rescue Beta-agonist [ Time Frame: end of each dosing period ]
  • Asthma Control Test Questionnaire [ Time Frame: end of each dosing period ]
    Patient reported outcome minimum 5 (no symptoms) maximum 25 (severe symptoms)
Original Secondary Outcome Measures  ICMJE
 (submitted: December 29, 2008)
  • FEV1 on drug vs placebo at end of 125 mg dosing period [ Time Frame: 17 weeks ]
  • Rescue Beta-agonist use during last week of each 125 mg dosing period. [ Time Frame: 17 weeks ]
  • Requirement for escalation of controller medication. [ Time Frame: 17 weeks ]
  • Requirement for urgent medical care for asthma. [ Time Frame: 17 weeks ]
  • Peak flow measurements during last 7 days of each dosing period. [ Time Frame: 17 weeks ]
  • Ability to taper systemic steroids among those patients who are on systemic steroids at study entry. [ Time Frame: 17 weeks ]
  • Acute FEV1 change 1, 2, 4 hours after initial 125 mg dose of bosentan. [ Time Frame: 17 weeks ]
  • Asthma control test questionnaire [ Time Frame: 17 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: September 28, 2012)
  • Requirement for Escalation of Controller Medication. [ Time Frame: 17 weeks ]
  • Requirement for Urgent Medical Care for Asthma. [ Time Frame: 17 weeks ]
  • Ability to Taper Systemic Steroids Among Those Patients Who Are on Systemic Steroids at Study Entry. [ Time Frame: 17 weeks ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bosentan for Poorly Controlled Asthma
Official Title  ICMJE The Effect of the ET-1 Receptor Antagonist, Bosentan on Patients With Poorly Controlled Asthma-A 17 Week, Double-blind, Placebo Controlled Crossover Trial
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 1 Crossover
Interventions:
  • Drug: bosentan
  • Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 8, 2010)
11
Original Estimated Enrollment  ICMJE
 (submitted: December 29, 2008)
20
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00815347
Other Study ID Numbers  ICMJE 08-287-1
001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mark Metersky, UConn Health
Study Sponsor  ICMJE UConn Health
Collaborators  ICMJE Actelion
Investigators  ICMJE
Principal Investigator: Mark L Metersky, MD UConn Health
PRS Account UConn Health
Verification Date September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP