Effect of Pre-Treatment With Cromolyn or Albuterol on Response to PUL-042 Inhalation Solution (PUL-042)

A Randomized, Open-label, Crossover Study to Assess the Safety, Tolerability, and Pharmacodynamics of PUL-042 Inhalation Solution in Healthy Subjects and the Effect of Pretreatment With Cromolyn Sodium or Albuterol Sulfate

This study evaluates the effect of pre-treatment with either cromolyn sodium or albuterol sulfate on the safety and tolerability or PUL-042 Inhalation Solution in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PUL-042 Inhalation Solution; Drug: Cromolyn Sodium; Drug: Albuterol sulfate

Detailed Description

Healthy subjects (8 per cohort) will be randomized to either pre-treatment or no pre-treatment (4 per group). The initial cohort will receive pre-treatment with cromolyn sodium. Subjects will be followed for 2 weeks for safety and tolerability, undergo a 2 week washout period and then be assigned to the alternative treatment (i.e., subjects who received cromolyn sodium prior to PUL-042 inhalation solution will not receive pretreatment) and then followed for an additional 2 weeks.

Subsequent cohort will receive pre-treatment with albuterol sulfate in a like manner.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females of non-childbearing potential (defined as surgically sterilized [tubal ligation/hysterectomy/bilateral salpingo oophorectomy or post- menopausal for > 2 years) with a negative urine human chorionic gonadotropin (hCG) pregnancy test at the Screening Visit
• Body Mass Index (BMI) between 18 and 30 kg/m2
• Ability to perform spirometry according to American Thoracic Society standards
• Normal spirometry (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC] ≥ 80% and ≤ 120% based on predicted values) at the Screening Visit and at Visit 2.
• Pulse oximetry ≥95% on room air
• Ability to understand and give informed consent
• Males willing to practice contraception (condom + spermicide) during the study and for 30 days after completion of the

Exclusion Criteria:

• Febrile (temperature ≥ 99.5°Fahrenheit)
• A history of use of any tobacco products during the year prior to the Screening Visit and a total exposure of > 5 pack years or a positive urine cotinine level at the Screening Visit
• Clinically significant laboratory finding as determined by the Principal Investigator or designee at the Screening Visit or at Visit 2
• Positive test for drugs of abuse (alcohol, cannabinoids, opiates, cocaine, amphetamine, barbiturates, benzodiazepine, phencyclidine)
• Any active medical problems requiring treatment
• Subjects who exhibit symptoms of respiratory infection or have experienced respiratory symptoms of an upper respiratory infection within 30 days prior to the Screening Visit.
• History of chronic pulmonary disease (eg, asthma [including atopic asthma, exercise induced asthma, or asthma triggered by respiratory infection], pulmonary fibrosis), pulmonary hypertension, or heart failure
• Any out of range QTc Fridericia (QTcF) or other clinically significant ECG findings as determined by the Principal Investigator or designee at Visit 2 or Visit 12.
• History of atopic reactions
• Administration of any anti-inflammatory therapy (eg, no steroidal anti-inflammatory drugs or corticosteroids) within 4 weeks prior to randomization or expected to be ongoing during the study
• An anticipated need for use of any inhaled medication during the study
• Intake of coffee, tea, cola drinks, chocolate on days of Study Visits 1-21
• Intake of alcohol, caffeine or strenuous exercise within 72 hours prior to study drug administration or intake of grapefruit within 7 days prior to the administration of study drug
• Intake of alcohol within 4 hours of spirometry; smoking within 1 hour of spirometry; performing vigorous exercise within 30 minutes of spirometry; wearing clothing that substantially restricts full chest and abdominal expansion; or eating a large meal within 2 hours of spirometry
• Administration of any over the counter (OTC)/prescription medication, supplements, herbals or vitamins within 14 days prior to study drug administration. Administration of Tylenol within 72 hours of study drug administration (doses up to 2g/day will be allowed prior to 72 hours before study drug administration)
• Exposure to any investigational agent within 30 days prior to the Screening Visit
• Receipt of a flu vaccine in the last 3 months
• Prior exposure to PUL-042
• Known positive for human immunodeficiency virus, or on active anti-retroviral therapy and known hepatitis B surface antigen positive or hepatitis C positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PUL-042; PUL-042 Inhalation Solution	Drug: PUL-042 Inhalation Solution; PUL-042
Experimental: Cromolyn sodium; Pre-Treatment with cromolyn sodium followed by PUL-042 Inhalation Solution Administration	Drug: PUL-042 Inhalation Solution; PUL-042; Drug: Cromolyn Sodium; Pre-treatment
Experimental: Albuterol sulfate; Pre-Treatment with albuterol sulfate followed by PUL-042 Inhalation Solution Administration	Drug: PUL-042 Inhalation Solution; PUL-042; Drug: Albuterol sulfate; Pre-treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment emergent, treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0)	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of pre-treatment with cromolyn sodium or albuterol sulfate on serial forced expiratory volume in 1 second (FEV1) from 0-8 hours post PUL-042 administration	Area under the FEV1 curve from dosing until 8 hours post-dose (AUC0-8)	8 hours
Number of participants with FEV1 decrease of > 12% compared to pred-dose baseline	Serial measurements of FEV1	2 weeks
Number of participants with absolute neutrophil count (ANC) outside the normal range	Serial measurements of ANC	2 weeks

Collaborators and Investigators

• Sponsor: Pulmotect, Inc.
• Collaborators: WCCT Global

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): August 10, 2017
• Last Update Submitted That Met QC Criteria: August 8, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Safety; tolerability
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Immunologic Factors; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Mast Cell Stabilizers; Albuterol; Cromolyn Sodium; Pam2CSK4 acetate and ODN M362 combination
• Other Study ID Numbers: PUL-042-003