Title
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
Phase
Phase 1Lead Sponsor
Pulmotect, Inc.Study Type
InterventionalStatus
Completed No Results PostedIndication/Condition
HealthyIntervention/Treatment
pul-042 ...Study Participants
42The 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.
Fixed dose combination of Pam2CSK4 acetate (Pam2) and ODN M362 (ODN) administered as an inhalation solution. Single dose administration by nebulization. Starting dose will be 2.9 micrograms Pam2: 4.25 micrograms ODN. Up to 7 doubling doses may be tested.
Sterile water for injection administered by nebulization
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
