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

Pulmotect

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: PUL-042 Inhalation Solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT02124278

PUL-042-001

Details and patient eligibility

About

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

Full description

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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups, including a placebo group

PUL-042 Inhalation Solution

Experimental group

Description:

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.

Treatment:

Drug: PUL-042 Inhalation Solution

Sterile water for injection

Placebo Comparator group

Description:

Sterile water for injection administered by nebulization

Treatment:

Drug: PUL-042 Inhalation Solution