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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PUL-042 Inhalation Solution
* Drug: Cromolyn Sodium
* Drug: Albuterol sulfate


Participation Criteria
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Eligibility Criteria
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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

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, tolerability