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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PUL-042 Inhalation Solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUL-042 Inhalation Solution<br>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. | Drug: PUL-042 Inhalation Solution<br> <br> |
| Placebo Comparator: Sterile water for injection<br>Sterile water for injection administered by nebulization | Drug: PUL-042 Inhalation Solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLTs) |  | Dosing to one week post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single ascending dose, Safety and tolerability in healthy subjects