Phase 1b Safety, Tolerability, and PK Study to Assess GS-5737 in Subjects With CF

Study Overview
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Brief Summary
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This study will determine the safety, tolerability, and pharmacokinetics of a single dose of GS-5737 administered with a 2.8% saline solution vehicle in adult subjects with CF.

Official Title
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A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Single Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of GS-5737 in Subjects With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: GS-5737
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ≥ 18 years of age, at Screening Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria, with at least 1 of the following: Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR Abnormal nasal transepithelial potential difference (NPD) test OR Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND 1 or more accompanying clinical features consistent with CF FEV1 ≥ 40% and ≤ 90% predicted BMI ≥ 19 and ≤ 30 kg/m2 Clinically stable with no evidence of significant new or acute respiratory symptoms Chest radiograph without significant acute findings; or chest radiograph, CT, or MRI obtained and interpreted within 90 days prior to enrollment, without acute findings and no significant intercurrent illness; chronic, stable findings are allowed 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 Estimated creatinine clearance ≥ 80 mL/min at Screening Negative drug tests; including alcohol Hepatitis B, C, & HIV Negative Surgically sterile or ≥ 12 months post-menopausal Non-pregnant females Exclusion Criteria: Experienced symptoms of recent acute upper or lower respiratory tract infection or acute pulmonary exacerbation requiring treatment within 2 weeks prior to Screening Plasma potassium ≥ 5 mEq/L Changes in chronic azithromycin use, bronchodilator (BD), dornase alfa, HS, physiotherapy technique or regimen, antibiotics or corticosteroid medications within 28 days prior to Screening History of sputum or throat swab culture yielding Burkholderia species within 2 years of Screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GS-5737<br>The GS-5737 85 μg dose is contained in 4 mL of 10 mM citrate buffer, pH 5.0 in 2.8% (w/v) saline. | Drug: GS-5737<br> <br> |
| Placebo Comparator: Placebo<br>The vehicle (placebo) control contains 10 mM citrate buffer, pH 5.0 in 2.8% (w/v) saline in 4 mL. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of GS-5737 |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CF, Cystic Fibrosis, PK