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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PUL-042 Inhalation Solution

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 77027
      • ICON Development Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PUL-042 Inhalation Solution; 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
Placebo Comparator: Sterile water for injection; Sterile water for injection administered by nebulization	Drug: PUL-042 Inhalation Solution

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pulmotect, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 25, 2014
• First Posted (Estimate): April 28, 2014

Study Record Updates

• Last Update Posted (Estimate): April 29, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Single ascending dose; Safety and tolerability in healthy subjects
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Respiratory System Agents; Pam2CSK4 acetate and ODN M362 combination
• Other Study ID Numbers: PUL-042-001