Evaluation of Regional Lung Deposition of Inhaled Saline Using the tPAD Device

Purpose: This is an early device characterization study to define the fraction of delivered aerosol generated by a novel nebulizer (tPAD) that deposits in conducting airways.

Design: Open label, cross-over design, using a standard oral nebulizer (PARI LC Star) as a comparator. The order of visits will be randomized.

Methods: Gamma scintigraphy will be performed following use of each device on separate study visits.

Primary Outcome: Fraction of inhaled particles that clears over 24 hours.

• tPAD Device (Device): A novel, transnasal aerosol generator
• PARI LC Star Nebulizer (Device): Standard oral nebulizer

Primary outcomes

• 24-hour clearance fraction [24 hours]: The percentage of initially deposited aerosol particles that clear over 24 hours will be measured with gamma scintigraphy after 24 hours

Secondary outcomes

• Central:Peripheral Deposition Ratio [0-4 minutes after deposition]: The ratio of labelled particles initially deposited in the central and peripheral lung zones will be assessed to characterize aerosol targeting of the lung

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

1. Subjects aged 18 to 65 years (inclusive), and with a body mass index (BMI) < 30 kg/m2.
2. Non-pregnant female subjects must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate "double-barrier" method (such as a diaphragm and condom); or, must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation.
3. Subjects who are in good health, as determined by a medical history and examination.
4. Subjects who have normal lung function with a FEV1 ≥80% predicted and a FEV1/FVC >70%.
5. Subjects who are capable of providing written informed consent in English to participate in the study.

Exclusion Criteria:

1. Subjects who have evidence of an upper or lower respiratory infection or clinically significant illness at entry or within 14 days of the start of dosing.
2. Subjects with lung diseases as defined by a FEV1 <80% or a FEV1/FVC <70%
3. Subjects on inhaled medications, such as short or long acting bronchodilators or inhaled corticosteroids, will be excluded.
4. Subjects with a history of allergy or intolerance to albuterol or hypertonic saline.
5. Subjects with active chronic or acute rhinosinusitis or other nasal or sinus abnormality or disease.
6. Subjects who have a present history of any clinically significant neurologic, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological disorder or disease, substance abuse, or any other major disorder or disease.
7. Subjects who have had radiation exposure within the past year that would cause them to exceed Federal Regulations of 15 Rem annually by participating in this study. The study team will determine this.
8. Subjects with a history of smoking within the last 3 months.
9. Subjects with a positive pregnancy test or who are pregnant or are nursing.
10. Subjects who, in the opinion of the Principal Investigator, should not participate in the study.
11. Subjects with a BMI >30 kg/m2
12. Subjects who are taller than Height >6'2"
13. Subjects who have facial hair that they are not willing to shave

• Scott Donaldson, MD, Principal investigator, University of North Carolina, Chapel Hill