This project is directed toward testing the hypothesis that Dehydroepiandrosterone Sulfate (DHEAS, PB005) administered as a sterile, nonpyrogenic, lyophilized, single-dose intravenous infusion in a dose escalation fashion is safe and efficacious as an adjunct treatment to the standard therapy regimen of patients presenting to an Emergency Room with acute exacerbations of asthma.
The specific aim i s to determine the benefits of adding PB005 to the standard therapy regimen. This study will be conducted in a dose-escalation fashion, with the primary purpose of establishing the safety of administering PB005 versus placebo in this patient population. Patients presenting to an Emergency Room with an acute exacerbation of asthma (>6hrs) will be eligible for screening for this study. Patients consenting to participate will receive a single 30-minute intravenous infusion of Test Drug that will be initiated between the second and third doses of beta2-agonist therapy. The Test Drug will be administered via an intravenous infusion using standard sterile technique over a period of at least 30 minutes. Standard beta2-agonist therapy will be administered to all study patients with the first three doses given at 20-minute intervals, followed by hourly doses for four hours. Intravenous corticosteroids will be administered to all study patients, prior to the start of the Test Drug infusion. In addition, patients will be prescribed a 5-day course of oral steroids (20 mg, twice a day) when they are released from the hospital following the 24-hour safety assessment. Safety assessments will be performed during the Screening evaluation (12 hour period), continuing through the 24-hour period after initiation of the Test Drug infusion, and at the Day 7 follow-up visit. Scheduled assessments will consist of medical history, asthma symptom evaluation, physical exams, cardiac monitoring (ECGs and Holter Monitoring), measurement of vital signs, spirometry, pulse oximetry, laboratory evaluations, and adverse experience reports. Asthma symptoms (dyspnea and wheezing) scores will be solicited from the patient at prescribed intervals. Patients will also be instructed to record asthma symptoms on a patient diary twice daily (a.m. and p.m.) during the one-week follow-up period, and will be asked to score symptoms during the Day 7 follow-up visit. Blood pressure, pulse, and respiratory rate will be recorded. Patients will be fitted with a Holter monitor from prior to initiation of the Test drug infusion through the 24 hour safety assessment. A baseline 12-lead ECG will be performed prior to the start of the Test Drug infusion at 30-45 minutes after completion of the Test Drug infusion, and at the 12-hour evaluation, just prior to patients release from the hospital. Serial spirometry will performed to assess study eligibility, safety, and drug efficacy. Oxygen saturation (O2 sat.) levels will be continuously monitored via pulse oximetry from the initial presentation to the Emergency Room until 12 hours after initiation of the Test Drug infusion. Bloom samples (15mL) for hematology and chemistry, and urine samples for urinalysis will be obtained upon presentation to the Emergency Room, at the 12-hour safety assessment, and during the Day 7 follow-up safety assessment.
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