Safety and Tolerability of Single Ascending Doses of PUL-042 Inhalation Solution in Healthy Subjects

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PUL-042 Inhalation Solution in Healthy Subjects

The purpose is to determine if single doses of PUL-042 inhalation solution are safe in healthy subjects.

The study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of PUL-042 inhalation solutions in healthy subjects.

Subjects will be enter a screening period of up to 14 days to determine eligibility. Subjects will be admitted to the Phase 1 unit the day prior to dosing and remain in the unit until 24 hours post-dose. Subjects will be seen in the clinic at 3 and 7 days post-dose

A modified 3+3 design will be used to determine the maximum tolerated dose (MTD) based on the occurrence of dose-limiting toxicities (DLTs) defined by Common Terminology Criteria for Adverse Events (CTCAE) v4. Additional specific DLTs will be defined as: 1) Hypoxia, defined as a non-artifactual drop in pulse oximetry to < 90% on room air, 2) A decrease in forced expiratory volume in one second (FEV1) of 12% or greater compared to the last observation prior to dosing, 3) Any evidence of bronchospasm or wheezing requiring medical intervention. Doses will be doubled until the maximum tolerated dose (MTD- defined as the largest dose with 0/6 or 1/6 DLTs) is reached.

Inclusion Criteria:

• Males or females of non-childbearing potential
• Body mass index between 18 and 30 kg/m2
• Normal spirometry
• Normal diffusing capacity of lung for carbon monoxide
• Normal pulse oximetry
• Males willing to practice contraception or have a female partner using contraception

Exclusion Criteria:

• Febrile
• Abnormal chest x-ray
• History of tobacco products within the last year and total exposure of > 5 pack/years
• Clinically significant laboratory findings
• History of chronic pulmonary disease
• History of atopic reactions
• Mediastinal lymphadenopathy
• Oral corticosteroid therapy within 4 weeks prior to randomization
• Alcohol, caffeine or strenuous exercise within 72 hours prior to dosing
• Grapefruit within 7 days prior to dosing
• Administration of concomitant medications within 14 days prior to dosing
• Exposure to any investigational agent with 30 days
• Significant concurrent illness
• Know positive for HIV, hepatitis B or hepatitis C
• Inability to tolerate a nebulization test with sterile water for injection
• Positive test for drugs of abuse