Cystic Fibrosis
Conditions
Brief summary
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).
Interventions
DRUGP-1037
P-1037 is a novel ENaC inhibitor
DRUGHypertonic Saline
4.2% saline solution
DRUGSaline
0.17% saline solution
Sponsors
Vertex Pharmaceuticals Incorporated
Parion Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (number of adverse events of P-1037 in treatment groups) | Day 15 | number of adverse events of P-1037 in treatment groups |
| Safety [change in forced expiratory volume in one second (FEV1) from predosing to 1 hour post dosing] | Day 1 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of P-1037 on Cystic Fibrosis Questionnaire - Revised (CFQ-R) | Day 15 | CFQ-R on Day 15 |
| Absolute change in FEV1 | Day 15 | change in FEV1, from baseline (immediately before first dose) to same time of day on Day 15 |
| Effect of P-1037 on (forced expiratory flow at 25%-75% of vital capacity (FEF25-75%) | Day 15 | FEF25-75% from baseline (immediately before first dose) to same time of day on Day 15 |
| Determine whether co-administration of hypertonic saline (HS) enhances the effect of P-1037 on FEV1 (FEV1 on Day 15) | Day 15 | FEV1 on 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) | Day 15 | change in FVC from baseline (immediately before first dose) to same time of day on Day 15 |
Countries
United States
Outcome results
None listed