A Safety and Tolerability Study OF PUR118 In Subjects With Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether PUR118 is safe and tolerable in a population of subjects with Cystic Fibrosis.

Official Title
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A Phase 1 Dose-escalation Study TO Evaluate the Safety and Tolerability of PUR118 and Placebo in Subjects With CF

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: PUR118


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or non-pregnant, non-lactating healthy female. Age 18 to 55 years of age (inclusive) on day of signing informed consent. Subject has a BMI of 17 or greater. Subject has a confirmed diagnosis of cystic fibrosis documented by a compatible clinical or radiographic presentation, and definitive accepted lab and clinical criteria (e.g., sweat chloride > 60 mEq/L or 2 disease causing CFTR mutations) OR is regularly attending a Consultant led clinic where the diagnosis of Cystic Fibrosis is not in doubt. Subject has an FEV1 ≥ 45% of predicted at screening. Subject has an oxygen saturation >92% on room air as determined by pulse oximetry at screening. Subject is a non-smoker or ex-smoker has not smoked for at least six months prior to screening. Subject is otherwise medically stable without clinically significant abnormal screening results that depart from their usual baseline level of health as a subject with CF. Must be willing and able to communicate in English and participate in the whole study. Must provide written informed consent. Exclusion Criteria: Subject has unstable lung disease, as defined by a change in medical regimen during the preceding 2-weeks, or a significant new finding on chest radiograph (pneumothorax, lobar/segmental collapse), or in the opinion of the Investigator, has had a decline in pulmonary status within the last year not considered a part of the usual, chronic progression of CF lung disease and part of their baseline health condition as a subject with CF. Subject has had an exacerbation of respiratory symptoms within the past 30 days that required initiation of a new or altered respiratory therapy. Subject had either an upper or lower respiratory illness within the 30 days prior to dosing days, or has symptoms from such an illness that have not resolved. Subject has a history of lung transplantation. Females of child bearing potential who are pregnant, or lactating. Females who are sexually active and either not surgically sterile or not willing to use an acceptable form of contraception Clinically significant abnormal biochemistry, haematology or urinalysis not consistent with CF as judged by the Investigator Failure to satisfy the Investigator of fitness to participate for any other reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUR118<br> | Drug: PUR118<br>* low dose and high dose for 3 doses, BID<br>|
| Placebo Comparator: Placebo<br> | Drug: PUR118<br>* low dose and high dose for 3 doses, BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Changes in clinical signs and symptoms from physical examination and chest examination, changes in clinical safety laboratory tests, vital signs, spirometry, lung clearance index, 24-hour sputum weight and volume, oxygen saturation, ECG, telemetry, and adverse events. | 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics | To assess impact of PUR118 on mobilization and expectorated volume of airway mucus secretions. To evaluate impact of PUR118 on measurements of lung function, including ventilation inhomogeneity, by both spirometry and measurement of the lung clearance index (LCI). To evaluate an impact of PUR118 on sputum, serum and plasma biomarkers related to airway inflammation. | 36 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Diseases, Respiratory Tract Diseases, Fibrosis