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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease; Cystic Fibrosis
• Intervention / Treatment: Drug: GS-5737

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of GS-5737	Adverse events, airway reactivity, pulse oximetry, physical examination, and clinical laboratory test findings, urine and plasma potassium levels, 12-lead ECG abnormalities and interval measurements, and vital sign measurements will be used to assess this outcome measure.	4 weeks or duration of study

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 14, 2013
• First Submitted That Met QC Criteria: February 14, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Estimate): March 20, 2014
• Last Update Submitted That Met QC Criteria: March 19, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Chronic Obstructive Pulmonary Disease; Respiratory health
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Cystic Fibrosis
• Other Study ID Numbers: GS-US-234-0103