A Phase 1 Study to Characterize the Effect of GS-5737 Enhancement of Mucociliary Clearance (MCC) in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, cross-over, vehicle-controlled study to determine whether GS-5737 in 2.8% saline accelerates mucociliary clearance (MCC) in healthy subjects, compared to vehicle of 2.8% saline alone.

Official Title
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A Phase 1, Randomized, Double-Blind, Cross-Over, Vehicle-Controlled, Single-Dose Study To Characterize The Effect of GS-5737 Enhancement of Mucociliary Clearance (MCC) In Healthy Subjects

Conditions
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Cystic Fibrosis, Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: GS-5737


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) from ≥ 19 to ≤ 30 kg/m2 Normal ECG, with no history or evidence of myocardial infarction, QT prolongation, or ventricular arrhythmias Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate(HR) History of lifetime smoking < 5 pack-years (ie, 1 pack per day x 1 year = 1 pack-year)and non-smokers of at least 60 days duration prior to Screening Negative screening tests for drugs of abuse (including alcohol) Hepatitis B (HBV) surface antigen negative Hepatitis C (HCV) antibody negative HIV-1, 2 antibody negative Male subjects who are sexually active must be willing to use highly effective contraception from the Baseline Visit through completion of the study and continuing for at least 90 days from the date of the last dose of study drug Male subjects must refrain from sperm donation from the Baseline Visit through completion of the study and continuing for at least 90 days from the date of the last dose of study drug Females of childbearing potential must have a negative serum pregnancy test Females of childbearing potential must agree to utilize protocol recommended highly effective contraception methods from Screening throughout the duration of study treatment and for 30 days following the last dose of study drug Exclusion Criteria: Female subjects who are pregnant or lactating History of anaphylactic reaction to any drug Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study drug dosing Presence or history of extrinsic allergy requiring treatment; hay fever is allowed unless it is active or has required treatment within the previous 2 months Have donated blood within 56 days of study dosing Presence or history of any pulmonary diseases (ie, asthma, emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis, interstitial lung disease) Major surgery within 6 months of Screening Experienced symptoms of recent acute upper or lower respiratory tract infection requiring treatment within the 2 weeks prior to Screening Have had any radiation in the past year that would cause the subject exceed recommended limits by participating in this study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cross-Over Sequence 1<br>85 μg GS-5737 in 2.8% saline or 2.8% saline alone (blinded) | Drug: GS-5737<br>* A single dose of GS-5737 in 2.8% saline<br>|
| Experimental: Cross-Over Sequence 2<br>2.8% saline alone or 85 μg GS-5737 in 2.8% saline (blinded) | Drug: GS-5737<br>* A single dose of GS-5737 in 2.8% saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of MCC from Whole Lung Compartment | The primary endpoint of this study will be the calculated area under the curve of MCC from the whole lung compartment, assessed through 60 minutes post isotope dosing (AUC-60min), which will provide a description of the MCC curve. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of MCC from Central and Peripheral Lung | This outcome measure will be the calculated area under the cuve of MCC from the central and peripheral lung assessed through 60 minutes post isotope dosing (AUC60min). | 4 weeks or duration of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory health, Cystic Fibrosis, Chronic Obstructive Pulmonary Disease