Clinical trial NCT02566252: Effect of Pre-Treatment With Cromolyn or Albuterol on Response to PUL-042 Inhalation Solution (PUL-042)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Safety
tolerability
Lead sponsor: Pulmotect, Inc.
Sponsor class: INDUSTRY
Collaborators: name: WCCT Global
First posted: 2015-10-02
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
measure: 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
timeFrame: 8 hours
measure: Number of participants with FEV1 decrease of > 12% compared to pred-dose baseline
timeFrame: 2 weeks
measure: Number of participants with absolute neutrophil count (ANC) outside the normal range
timeFrame: 2 weeks
Locations:
city: Cypress
country: United States
facility: WCCT Global
state: California
Study officials:
affiliation: West Coast Clinical Trials
name: Michelle Ababa, MD
role: PRINCIPAL_INVESTIGATOR
References: