Clearing Lungs With Epithelial Sodium Channel (ENaC) Inhibition in Cystic Fibrosis (CF)

Study Overview
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Brief Summary
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The goal of the study is to evaluate the safety and tolerability of P-1037 and to determine whether the combination of P-1037 with hypertonic saline or P-1037 alone has a greater effect on lung function in patients with CF than placebo (0.17% saline).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of P-1037 Solution for Inhalation in Patients With Cystic Fibrosis (CF)

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: P-1037
* Drug: Hypertonic Saline
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 12 years of age or older. Diagnosis of cystic fibrosis as determined by the 1997 CF Consensus criteria (NIH Consensus Statement, 1997) Non-smoker FEV1 at Screening Visit 1 between 40% and 90% Stable regimen of CF medications and chest physiotherapy for the 28 days prior to Screening. Must be willing to discontinue use of hypertonic saline for the duration of the study. Clinically stable for at least 2 weeks All females of child-bearing potential must have a negative serum pregnancy test and if sexually active must agree to practice a highly effective form of contraception throughout the study and for 28 days after the last dose of study medication. Exclusion Criteria: History of any organ transplantation or any significant disease or disorder Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs or trimethoprim in the 28 days prior to Screening History of significant intolerance to inhaled hypertonic saline, as determined by the Investigator Known hypersensitivity to the study drug or amiloride Any clinically significant laboratory abnormalities at Screening Visit 1 as judged by the investigator, or any of the following: Potassium ≥ 5 milliequivalent per Liter (mEq/L) Abnormal renal function Abnormal liver function, defined as ≥ 3 x upper limit of normal (ULN) Hemoglobin level < 10.0 g/dL Female who is pregnant or lactating History of sputum or throat swab culture yielding Burkholderia species or Mycobacterium abscessus within 2 years of screening Has previously participated in an investigational trial involving administration of any investigational compound or use of an investigational device with 28 days prior to Screening Currently being treated with any ivacaftor containing regimen

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-1037 in Hypertonic Saline (HS)<br>P-1037 Solution for Inhalation, 85 μg twice daily (BID) (28.3 μg/mL) in hypertonic saline (4.2% saline) BID | Drug: P-1037<br>* P-1037 is a novel ENaC inhibitor<br>Drug: Hypertonic Saline<br>* 4.2% saline solution<br>|
| Experimental: P-1037 in Saline<br>P-1037 Solution for Inhalation, 85 μg BID (28.3 μg/mL) in 0.17% saline BID | Drug: P-1037<br>* P-1037 is a novel ENaC inhibitor<br>Drug: Saline<br>* 0.17% saline solution<br>|
| Placebo Comparator: Saline<br>Placebo (0.17% saline) BID | Drug: Saline<br>* 0.17% saline solution<br>|
| Sham Comparator: Hypertonic Saline<br>Hypertonic saline (4.2% saline) BID | Drug: Hypertonic Saline<br>* 4.2% saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (number of adverse events of P-1037 in treatment groups) | number of adverse events of P-1037 in treatment groups | Day 15 | 
| Safety [change in forced expiratory volume in one second (FEV1) from predosing to 1 hour post dosing] | change in FEV1 from predosing to 1 hour post dosing with P-1037 in 4.2 % hypertonic saline and P-1037 in 0.17% saline | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in FEV1 | change in FEV1, from baseline (immediately before first dose) to same time of day on Day 15 | Day 15 | 
| Effect of P-1037 on other forced vital capacity (FVC) measures (change in FVC from baseline (immediately before first dose) to same time of day on Day 15) | change in FVC from baseline (immediately before first dose) to same time of day on Day 15 | Day 15 | 
| Effect of P-1037 on Cystic Fibrosis Questionnaire - Revised (CFQ-R) | CFQ-R on Day 15 | Day 15 | 
| Determine whether co-administration of hypertonic saline (HS) enhances the effect of P-1037 on FEV1 (FEV1 on Day 15) | FEV1 on Day 15 | Day 15 | 
| Effect of P-1037 on (forced expiratory flow at 25%-75% of vital capacity (FEF25-75%) | FEF25-75% from baseline (immediately before first dose) to same time of day on Day 15 | Day 15 |