Cystic Fibrosis, PulmonaryPhase 1/2NCT04375514

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

A Phase 1/2 study testing ARO-ENaC in people with Cystic Fibrosis, Pulmonary, run by Arrowhead Pharmaceuticals at 7 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of single doses of ARO-ENaC in healthy adult volunteers; and to evaluate the safety, tolerability, PK and efficacy of multiple doses of ARO-ENaC in patients with pulmonary cystic fibrosis. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Cystic Fibrosis, Pulmonary
What is being tested?: ARO-ENaC
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 43 participants
Where: 7 sitesin 2 countries
Study dates: 30 Jul 2020to 13 May 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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)

Who cannot join

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

Show all 13Show fewer

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

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

Australia4 sites

Research Site 3
Chermside, Queensland, 4032
Research Site 2
Hamilton, 3204
Research Site 1
Nedlands, Washington, 6009
Research Site 4
South Brisbane, Queensland, 4101

Other trials in Australia

New Zealand3 sites

Research Site 8
Christchurch, 8140
Research Site 7
Dunedin, 9054
Research Site 6
Grafton, Auckland, 1010

Other trials in New Zealand

About this study

Official title: A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-ENaC in Normal Healthy Volunteers and Safety, Tolerability and Efficacy in Patients With Cystic Fibrosis

Conditions: Cystic Fibrosis, Pulmonary
Being tested: ARO-ENaC, Placebo
Medical subject headings: Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ARO-ENaCDrug
single or multiple doses of ARO-ENaC by inhalation of nebulized solution
PlaceboDrug
calculated volume of normal saline to match active treatment by inhalation of nebulized solution

Study groups in NCT04375514
Study group	Role	What they receive
Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3	Experimental	Normal healthy volunteers receive double-blind ARO-ENaC 20 mg on Days 1, 2, 3 Receives: Drug: ARO-ENaC
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3	Placebo comparator	Normal healthy volunteers receive double-blind placebo for ARO-ENaC 20 mg on Days 1, 2, 3 Receives: Drug: Placebo
Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3	Experimental	Normal healthy volunteers receive double-blind ARO-ENaC 40 mg on Days 1, 2, 3 Receives: Drug: ARO-ENaC
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3	Placebo comparator	Normal healthy volunteers receive double-blind placebo for ARO-ENaC 40 mg on Days 1, 2, 3 Receives: Drug: Placebo
Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3	Experimental	Normal healthy volunteers receive double-blind ARO-ENaC 65 mg on Days 1, 2, 3 Receives: Drug: ARO-ENaC
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3	Placebo comparator	Normal healthy volunteers receive double-blind placebo for ARO-ENaC 65 mg on Days 1, 2, 3 Receives: Drug: Placebo
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3	Experimental	Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 Receives: Drug: ARO-ENaC
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3	Placebo comparator	Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 Receives: Drug: Placebo
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	Experimental	Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 with the purpose of collecting bronchoscopic samples Receives: Drug: ARO-ENaC
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	Placebo comparator	Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples Receives: Drug: Placebo
Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24	Experimental	Participants with cystic fibrosis receive double-blind ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and 40 mg dosed on Days 22, 23, and 24 Receives: Drug: ARO-ENaC
Cystic Fibrosis Cohort: Placebo	Placebo comparator	Participants with cystic fibrosis receive double-blind placebo for ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and Days 22, 23, and 24. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AEs)
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.
Measured: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose

Secondary outcomes (15)

Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride
Measured: Normal Healthy Volunteers: Baseline, Days 2, 3, 4, 8, 15, 18, 29 ; Participants with CF: Baseline, Days 2, 3, 4, 15, 22, 23. 24, 29, 37, 57, 71, 85, 91, 113
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
Measured: Baseline, Up through Day 29 after a single dose
Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Cmax in Participants With CF
Measured: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Tmax in Participants With CF
Measured: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: AUClast in Participants With CF
Measured: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: CL/F in Participants With CF
Measured: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers
Measured: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jul 202013 May 2022

First posted5 May 2020
Study start30 Jul 2020
Primary completion9 May 2021
Study completion13 May 2022

Why it stopped: Business decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cystic Fibrosis, PulmonaryStudies of the same condition, open and under way.
More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04375514
Sponsor's protocol ID: AROENaC1001
Status last verified: Dec 2025
First submitted: 30 Apr 2020
Last updated: 17 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Early Study on Tamoxifen Safety/Tolerability in Cystic Fibrosis Patients Unable to Use CFTR Modulators.
Cystic Fibrosis - Complete
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Cystic Fibrosis (CF)

All Cystic Fibrosis, Pulmonary trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-ENaC in Normal Healthy Volunteers and Safety, Tolerability and Efficacy in Patients With Cystic Fibrosis
ClinicalTrials.gov ID: NCT04375514
Acronym / sponsor ID: AROENaC1001
Conditions: Cystic Fibrosis, Pulmonary
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Business decision
Enrolment: 43 participants (actual)
Lead sponsor: Arrowhead PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 30 Jul 2020 (actual)
Primary completion: 9 May 2021 (actual)
Study completion: 13 May 2022 (actual)
First posted: 5 May 2020 (actual)
Results: Posted 17 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 12

Arm	Type	Receives
Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3	Experimental	Drug: ARO-ENaCNormal healthy volunteers receive double-blind ARO-ENaC 20 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3	Placebo comparator	Drug: PlaceboNormal healthy volunteers receive double-blind placebo for ARO-ENaC 20 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3	Experimental	Drug: ARO-ENaCNormal healthy volunteers receive double-blind ARO-ENaC 40 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3	Placebo comparator	Drug: PlaceboNormal healthy volunteers receive double-blind placebo for ARO-ENaC 40 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3	Experimental	Drug: ARO-ENaCNormal healthy volunteers receive double-blind ARO-ENaC 65 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3	Placebo comparator	Drug: PlaceboNormal healthy volunteers receive double-blind placebo for ARO-ENaC 65 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3	Experimental	Drug: ARO-ENaCNormal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3	Placebo comparator	Drug: PlaceboNormal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	Experimental	Drug: ARO-ENaCNormal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 with the purpose of collecting bronchoscopic samples
Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	Placebo comparator	Drug: PlaceboNormal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples
Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24	Experimental	Drug: ARO-ENaCParticipants with cystic fibrosis receive double-blind ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and 40 mg dosed on Days 22, 23, and 24
Cystic Fibrosis Cohort: Placebo	Placebo comparator	Drug: PlaceboParticipants with cystic fibrosis receive double-blind placebo for ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and Days 22, 23, and 24.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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)

Key exclusion criteria (13 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ARO-ENaCsingle or multiple doses of ARO-ENaC by inhalation of nebulized solution	Drug	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24, Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3, Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy, Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3, Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3, Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3
Placebocalculated volume of normal saline to match active treatment by inhalation of nebulized solution	Drug	Cystic Fibrosis Cohort: Placebo, Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3, Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy, Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3, Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3, Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3

Primary outcome

Number of Participants With Adverse Events (AEs)
Time frame: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

15 secondary outcomes

Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride
Time frame: Normal Healthy Volunteers: Baseline, Days 2, 3, 4, 8, 15, 18, 29 ; Participants with CF: Baseline, Days 2, 3, 4, 15, 22, 23. 24, 29, 37, 57, 71, 85, 91, 113
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
Time frame: Baseline, Up through Day 29 after a single dose
Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Cmax in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Tmax in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: AUClast in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: CL/F in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)

Results and safety

Results posted to the registry on 17 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3	4	4
Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3	4	4
Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3	4	4
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3	4	4
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	8	8
Normal Healthy Volunteer Cohort: Pooled Placebo	12	12
Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24	4	4
Cystic Fibrosis Cohort: Placebo	3	3

Primary outcome: Number of Participants With Adverse Events (AEs)

Time frame: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose. Count of participants. Unit: Participants

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n = 4	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n = 4	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n = 4	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n = 4	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n = 8	Normal Healthy Volunteer Cohort: Pooled Placebo n = 12	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n = 4	Cystic Fibrosis Cohort: Placebo n = 3
Any AE	3	2	3	3	6	10	3	3
Any TEAE	2	2	3	2	6	8	3	3
Any Treatment-Related TEAE	1	1	2	2	1	5	2	1
Any SAE	0	0	0	0	1	0	1	2
Any TE SAE	0	0	0	0	1	0	1	2
Any Treatment-Related TE SAE	0	0	0	0	0	0	1	0
Any AE Resulting in Study Drug Withdrawal	0	0	0	0	0	0	0	0
Any AE Resulting in Study Discontinuation	0	0	0	0	0	0	0	0

Population analysed: Safety Set (all enrolled participants who received at least one dose of active drug or placebo)

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy	1 of 8 (12.5%)	6 of 8 (75%)	0 of 8
Normal Healthy Volunteer Cohort: Pooled Placebo	0 of 12 (0%)	10 of 12 (83.3%)	0 of 12
Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24	1 of 4 (25%)	3 of 4 (75%)	0 of 4
Cystic Fibrosis Cohort: Placebo	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3

Limitations and caveats (from the sponsor): On 01 July 2021 a voluntary suspension of dosing by the Sponsor was initiated. All subjects who had completed all planned doses continued safety follow-up according to the scheduled activities. This suspension of dosing was due to preliminary findings in the 6-month chronic rat good laboratory practice (GLP) toxicology study. The voluntary suspension was unrelated to any safety findings in the AROENaC1001 study. Subsequent to this, the Sponsor decided to terminate the AROENaC1001 study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ARO-ENaC in people with Cystic Fibrosis, Pulmonary, run by Arrowhead Pharmaceuticals at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) (time frame: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04375514.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.