Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis

Recruitment & Eligibility

Inclusion Criteria

Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
Willing to provide written informed consent and to comply with study requirements
Normal electrocardiogram (ECG) at Screening
Non-smoking
Normal pulmonary function tests at Screening (NHVs only)
No abnormal finding of clinical relevance at Screening other than CF for CF patients
Confirmed diagnosis of CF based on source verifiable medical record (CF patients only)
All other treatments for CF have been stable for at least 2 months and patient is willing to continue this treatment regimen without change for duration of study (CF patients only)

Exclusion Criteria

Acute lower respiratory infection within 30 days of Screening (NHVs only)
History of asthma (specifically, those subjects at risk of bronchial hyperactivity), anaphylaxis or airway hyper-reactivity
Clinically significant history of hyperkalemia or presence of hyperkalemia at Screening
Clinically significant health concerns (other than CF in CF patients)
Human Immunodeficiency virus (HIV) infection, seropositive for Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
Uncontrolled hypertension
Excessive use of alcohol within one month prior to Screening
Use of illicit drugs within 1 year prior to Screening
Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
CF exacerbation within 30 days of Dosing (CF patients)
History of solid organ transplant (CF patients)
Diagnosis of hepatic cirrhosis (CF patients)

Note: additional inclusion/exclusion criteria may apply per protocol

Study & Design

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Sterile normal saline (0.9% NaCl)
ARO-ENaC	ARO-ENaC	ARO-ENaC Inhalation

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment	single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF

Secondary Outcome Measures

Name	Time	Method
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
Change from Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride (all in mmol/L)	Baseline, single dose phase: Up to 29 (+/- 2) days; multiple dose phase: Up to 113 (+/- 5 days) post-dose for patients with CF
Change from Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers	Baseline, Up through Day 29 after a single dose
PK of ARO-ENaC: Maximum observed Plasma Concentration (Cmax)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Terminal Elilmination Half-Life (t1/2)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)	single dose phase: Up through Day 5; multiple dose phase: Up through Day 30 (+/- 2 days)

Recruitment & Eligibility