Single Dose Escalating Study of DAS181 in Adults

Primary Outcome Measures:

• Safety and tolerability of a single-dose of DAS181 treatment at 0.5 mg, 1.0 mg, 2.25 mg, and 4.5 mg. [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  

Secondary Outcome Measures:

• The pharmacokinetic parameters of DAS181. [ Time Frame: Pre-dosing, 1, 2, 4, 6, 8, 12 and 24 hours post dosing, Day 2, and Day 7 ] [ Designated as safety issue: No ]
  

The objective of this study is to investigate the safety, tolerability and pharmacokinetics of a single dose of DAS181 encapsulated dry powder compared to placebo when administered by oral inhalation using a dry powder inhaler in healthy adults. Primary study outcome measures are the safety and tolerability of single-dose DAS181 treatment at 0.5 mg, 1.0 mg, 2.25 mg, and 4.5 mg, as measured in the following parameters: adverse events, physical exam, vital signs, hematology, clinical chemistry, blood coagulation, complement activation, haptoglobin and immunogenicity, urinalysis, throat swab for bacterial culture, ECG, chest X-ray, and spirometric lung function. Secondary outcome measures are the systemic exposure and pharmacokinetic parameters of DAS181. This phase 1 study will be a double-blind, randomized, placebo-controlled, single-dose escalation study conducted at Comprehensive Phase One Miramar campus. Thirty-six to 60 healthy male and female volunteers, 18-65 years (inclusive), will be enrolled in 4 separate steps. Each enrollment will recruit 9 subjects for one of the 4 dose groups. Within each dose group, the participants will be randomly assigned to placebo or DAS181, at 1:2 ratios. The subjects will receive a single-dose treatment by placebo (10.5 mg lactose), or by DAS181 at one of 4 doses: 0.5 mg, 1.0 mg, 2.25 mg, and 4.5 mg. The subjects will be screened and enrolled within 28 days prior to dosing of the study drug. The study will be initiated with 0.5 mg dose. Escalation to the next dose will be contingent upon meeting the dose escalation criteria after the study day 7 post dosing follow-up visit (Visit 4). The day of dosing is always defined as Day 0 (or study day 0), regardless of the step or cohort. All future visits and time periods are referenced to the day of dosing. Administration of DAS181 or placebo will be given under the supervision of the study staff. Subjects will enter the inpatient clinic on day -1, the evening prior to dosing. Subjects will remain in the inpatient clinic for 24 hours post exposure to be observed for signs of adverse events (AEs). After the 24-hour inpatient observation period, participants will be discharged if they are deemed healthy at that point. All subjects must come back for follow-up visits on the following study days: 2, 7, 14 (±1 day), and 30 (±2 days).