Bosentan for Poorly Controlled Asthma

NCT00815347 | Terminated Phase 2 Results DMC

• 2 other identifiers: 08-287-1001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Asthma

Outcome Measures

Primary Outcomes (3)

• Change in FEV1

  1, 2, 4 hours after dosing

• Peak Flow

  last 7 days of each dosing period

• Symptom Scores

  Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)

  Last 7 days of each dosing period

Secondary Outcomes (3)

• FEV1

  end of dosing period

• Rescue Beta-agonist

  end of each dosing period

• Asthma Control Test Questionnaire

  end of each dosing period

Other Outcomes (3)

• Requirement for Escalation of Controller Medication.

  17 weeks

• Requirement for Urgent Medical Care for Asthma.

  17 weeks

• Ability to Taper Systemic Steroids Among Those Patients Who Are on Systemic Steroids at Study Entry.

  17 weeks

Study Arms (1)

1 Crossover

OTHER

Drug: bosentan; Drug: placebo

Interventions

bosentan DRUG

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.

1 Crossover

placebo DRUG

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.

1 Crossover

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UConn Health: lead
• Actelion: collaborator

Study Sites (1)

University of Connecticut Health Center

Farmington, Connecticut, 06030-2810, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: MArk Metersky, MD
• Organization: University of Connecticut Health Center

metersky@nso.uchc.edu

860-679-3582

Study Officials

• Mark L Metersky, MD

  UConn Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 29, 2008
• First Posted: December 30, 2008
• Study Start: December 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: October 1, 2012
• Results First Posted: October 1, 2012

Record last verified: 2012-09

Locations

US (1)