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Bosentan for Poorly Controlled Asthma

Primary Purpose

Asthma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bosentan
placebo
Sponsored by
UConn Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Asthma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Connecticut Health Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

1 Crossover

Arm Description

Outcomes

Primary Outcome Measures

Change in FEV1
Peak Flow
Symptom Scores
Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)

Secondary Outcome Measures

FEV1
Rescue Beta-agonist
Asthma Control Test Questionnaire
Patient reported outcome minimum 5 (no symptoms) maximum 25 (severe symptoms)

Full Information

First Posted
December 29, 2008
Last Updated
September 28, 2012
Sponsor
UConn Health
Collaborators
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT00815347
Brief Title
Bosentan for Poorly Controlled Asthma
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 Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Terminated
Why Stopped
Difficulty in recruitment.
Study Start Date
December 2008 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UConn Health
Collaborators
Actelion

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark L Metersky, MD
Organizational Affiliation
UConn Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030-2810
Country
United States

12. IPD Sharing Statement

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Bosentan for Poorly Controlled Asthma

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