Trial Outcomes & Findings for Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis (NCT NCT04375514)

NCT ID: NCT04375514

Last Updated: 2025-12-17

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose
• Results posted on: 2025-12-17

Participant Flow

Following Screening, eligible normal healthy volunteer participants enrolled and were randomly assigned 2:1 to receive ARO-ENaC or placebo on Days 1-3. Per protocol, the placebo cohorts were pooled for data analysis. Participants with cystic fibrosis were randomly assigned 2:1 to receive ARO-ENaC or placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.

Participant milestones

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Overall Study STARTED	4	4	4	4	8	12	4	3
Overall Study COMPLETED	4	4	4	4	8	12	4	3
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 Participants Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n=4 Participants Participants with cystic fibrosis received 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 n=3 Participants Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.	Total n=43 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	0 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=6 Participants	4 Participants n=5 Participants	4 Participants n=5 Participants	4 Participants n=122 Participants	8 Participants n=488 Participants	12 Participants n=182 Participants	4 Participants n=3 Participants	3 Participants n=10 Participants	43 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	0 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	0 Participants n=6 Participants	3 Participants n=5 Participants	3 Participants n=5 Participants	2 Participants n=122 Participants	2 Participants n=488 Participants	8 Participants n=182 Participants	2 Participants n=3 Participants	3 Participants n=10 Participants	23 Participants n=27 Participants
Sex: Female, Male Male	4 Participants n=6 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants	2 Participants n=122 Participants	6 Participants n=488 Participants	4 Participants n=182 Participants	2 Participants n=3 Participants	0 Participants n=10 Participants	20 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	0 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=6 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants	0 Participants n=122 Participants	1 Participants n=488 Participants	3 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	7 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	1 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	1 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	2 Participants n=6 Participants	2 Participants n=5 Participants	3 Participants n=5 Participants	2 Participants n=122 Participants	5 Participants n=488 Participants	7 Participants n=182 Participants	4 Participants n=3 Participants	3 Participants n=10 Participants	28 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	1 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	0 Participants n=488 Participants	1 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	2 Participants n=122 Participants	0 Participants n=488 Participants	1 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	1 Participants n=122 Participants	0 Participants n=488 Participants	1 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 Participants n=6 Participants	3 Participants n=5 Participants	2 Participants n=5 Participants	2 Participants n=122 Participants	3 Participants n=488 Participants	7 Participants n=182 Participants	4 Participants n=3 Participants	3 Participants n=10 Participants	27 Participants n=27 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=122 Participants	1 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	1 Participants n=122 Participants	2 Participants n=488 Participants	0 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Other	1 Participants n=6 Participants	1 Participants n=5 Participants	2 Participants n=5 Participants	0 Participants n=122 Participants	2 Participants n=488 Participants	4 Participants n=182 Participants	0 Participants n=3 Participants	0 Participants n=10 Participants	10 Participants n=27 Participants

PRIMARY outcome

Timeframe: Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose

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

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.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 Participants Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n=4 Participants Participants with cystic fibrosis received 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 n=3 Participants Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Number of Participants With Adverse Events (AEs) Any AE	3 Participants	2 Participants	3 Participants	3 Participants	6 Participants	10 Participants	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Any TEAE	2 Participants	2 Participants	3 Participants	2 Participants	6 Participants	8 Participants	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Any Treatment-Related TEAE	1 Participants	1 Participants	2 Participants	2 Participants	1 Participants	5 Participants	2 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Any TE SAE	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Any Treatment-Related TE SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE Resulting in Study Drug Withdrawal	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE Resulting in Study Discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE Resulting in Death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Population: Safety Set: all enrolled participants who received at least one dose of active drug or placebo. Participants with an assessment at given time point.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 Participants Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n=4 Participants Participants with cystic fibrosis received 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 n=3 Participants Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 18	—	—	—	—	-0.16 mmol/L Standard Deviation 0.50	0.20 mmol/L Standard Deviation 0.27	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 22	—	—	—	—	—	—	-0.10 mmol/L Standard Deviation 0.245	-0.27 mmol/L Standard Deviation 0.306
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 23	—	—	—	—	—	—	-0.05 mmol/L Standard Deviation 0.370	-0.07 mmol/L Standard Deviation 0.153
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 24	—	—	—	—	—	—	-0.03 mmol/L Standard Deviation 0.171	0.07 mmol/L Standard Deviation 0.321
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 29	-0.15 mmol/L Standard Deviation 0.65	0.18 mmol/L Standard Deviation 0.45	-0.33 mmol/L Standard Deviation 0.22	0.05 mmol/L Standard Deviation 0.17	-0.09 mmol/L Standard Deviation 0.37	0.03 mmol/L Standard Deviation 0.24	-0.05 mmol/L Standard Deviation 0.173	0.00 mmol/L Standard Deviation 0.300
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 37	—	—	—	—	—	—	0.13 mmol/L Standard Deviation 0.330	0.07 mmol/L Standard Deviation 0.404
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 57	—	—	—	—	—	—	-0.05 mmol/L Standard Deviation 0.311	-0.10 mmol/L Standard Deviation 0.200
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 71	—	—	—	—	—	—	0.03 mmol/L Standard Deviation 0.275	0.10 mmol/L Standard Deviation 0.265
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 85	—	—	—	—	—	—	0.10 mmol/L Standard Deviation 0.356	-0.25 mmol/L Standard Deviation 0.071
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 91	—	—	—	—	—	—	0.03 mmol/L Standard Deviation 0.403	-0.10 mmol/L Standard Deviation 0.283
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 113	—	—	—	—	—	—	-0.03 mmol/L Standard Deviation 0.321	0.07 mmol/L Standard Deviation 0.153
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 2	0.0 mmol/L Standard Deviation 1.4	-0.8 mmol/L Standard Deviation 1.7	0.0 mmol/L Standard Deviation 1.4	1.5 mmol/L Standard Deviation 3.3	1.1 mmol/L Standard Deviation 1.5	0.3 mmol/L Standard Deviation 0.9	-0.5 mmol/L Standard Deviation 1.91	-1.3 mmol/L Standard Deviation 0.58
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 3	-0.3 mmol/L Standard Deviation 1.7	1.3 mmol/L Standard Deviation 1.7	-1.0 mmol/L Standard Deviation 0.8	-0.3 mmol/L Standard Deviation 2.9	0.9 mmol/L Standard Deviation 1.0	-0.3 mmol/L Standard Deviation 1.6	1.0 mmol/L Standard Deviation 2.71	0.3 mmol/L Standard Deviation 4.04
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 4	-1.3 mmol/L Standard Deviation 1.5	-0.3 mmol/L Standard Deviation 1.9	0.3 mmol/L Standard Deviation 2.2	5.0 mmol/L Standard Deviation 2.0	0.4 mmol/L Standard Deviation 1.4	0.8 mmol/L Standard Deviation 1.5	0.5 mmol/L Standard Deviation 1.73	-0.7 mmol/L Standard Deviation 2.52
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 8	2.0 mmol/L Standard Deviation 2.2	2.5 mmol/L Standard Deviation 1.7	0.5 mmol/L Standard Deviation 2.4	1.5 mmol/L Standard Deviation 1.3	2.0 mmol/L Standard Deviation 1.7	-0.3 mmol/L Standard Deviation 1.9	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 15	0.8 mmol/L Standard Deviation 1.7	0.0 mmol/L Standard Deviation 2.6	0.0 mmol/L Standard Deviation 1.4	-1.0 mmol/L Standard Deviation 3.3	—	-0.6 mmol/L Standard Deviation 1.6	-0.5 mmol/L Standard Deviation 0.58	-1.3 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 18	—	—	—	—	2.5 mmol/L Standard Deviation 1.9	2.3 mmol/L Standard Deviation 2.4	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 22	—	—	—	—	—	—	1.0 mmol/L Standard Deviation 1.83	0.3 mmol/L Standard Deviation 3.21
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 23	—	—	—	—	—	—	1.5 mmol/L Standard Deviation 2.38	0.7 mmol/L Standard Deviation 3.79
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 24	—	—	—	—	—	—	2.0 mmol/L Standard Deviation 3.92	1.3 mmol/L Standard Deviation 5.77
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 29	-0.5 mmol/L Standard Deviation 1.7	1.8 mmol/L Standard Deviation 1.3	-0.3 mmol/L Standard Deviation 1.3	1.5 mmol/L Standard Deviation 4.5	1.8 mmol/L Standard Deviation 2.6	0.6 mmol/L Standard Deviation 1.7	-0.5 mmol/L Standard Deviation 1.91	0.0 mmol/L Standard Deviation 1.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 37	—	—	—	—	—	—	0.0 mmol/L Standard Deviation 2.45	-0.7 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 57	—	—	—	—	—	—	0.3 mmol/L Standard Deviation 2.22	-1.3 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 71	—	—	—	—	—	—	1.3 mmol/L Standard Deviation 0.50	-0.3 mmol/L Standard Deviation 0.58
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 85	—	—	—	—	—	—	1.0 mmol/L Standard Deviation 1.15	0.0 mmol/L Standard Deviation 1.41
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 91	—	—	—	—	—	—	1.0 mmol/L Standard Deviation 1.83	0.0 mmol/L Standard Deviation 1.41
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Sodium: Change at Day 113	—	—	—	—	—	—	-1.0 mmol/L Standard Deviation 2.65	-2.0 mmol/L Standard Deviation 1.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 2	0.0 mmol/L Standard Deviation 0.8	0.0 mmol/L Standard Deviation 0.8	0.5 mmol/L Standard Deviation 1.7	-4.8 mmol/L Standard Deviation 4.2	0.4 mmol/L Standard Deviation 1.8	-0.3 mmol/L Standard Deviation 2.5	1.8 mmol/L Standard Deviation 1.71	0.7 mmol/L Standard Deviation 3.79
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 3	-2.0 mmol/L Standard Deviation 0.8	-0.5 mmol/L Standard Deviation 1.7	0.5 mmol/L Standard Deviation 1.0	-1.0 mmol/L Standard Deviation 2.4	0.9 mmol/L Standard Deviation 1.4	-0.3 mmol/L Standard Deviation 1.6	-1.0 mmol/L Standard Deviation 2.16	0.7 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 4	-0.5 mmol/L Standard Deviation 0.6	1.3 mmol/L Standard Deviation 1.3	1.0 mmol/L Standard Deviation 0.8	0.0 mmol/L Standard Deviation 1.6	1.1 mmol/L Standard Deviation 1.4	0.2 mmol/L Standard Deviation 2.0	2.8 mmol/L Standard Deviation 2.50	1.3 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 8	-0.8 mmol/L Standard Deviation 2.1	1.3 mmol/L Standard Deviation 1.0	-0.3 mmol/L Standard Deviation 2.1	1.3 mmol/L Standard Deviation 1.3	1.9 mmol/L Standard Deviation 1.5	0.3 mmol/L Standard Deviation 1.9	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 15	-0.3 mmol/L Standard Deviation 0.5	1.0 mmol/L Standard Deviation 1.2	-0.3 mmol/L Standard Deviation 0.5	-0.5 mmol/L Standard Deviation 1.3	—	-1.0 mmol/L Standard Deviation 1.1	2.0 mmol/L Standard Deviation 1.41	0.7 mmol/L Standard Deviation 3.21
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 18	—	—	—	—	1.3 mmol/L Standard Deviation 1.4	1.8 mmol/L Standard Deviation 1.5	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 22	—	—	—	—	—	—	1.3 mmol/L Standard Deviation 2.63	0.3 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 23	—	—	—	—	—	—	1.0 mmol/L Standard Deviation 1.41	0.7 mmol/L Standard Deviation 0.58
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 24	—	—	—	—	—	—	1.3 mmol/L Standard Deviation 2.22	-1.3 mmol/L Standard Deviation 5.13
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 29	-0.5 mmol/L Standard Deviation 1.3	0.8 mmol/L Standard Deviation 1.0	0.0 mmol/L Standard Deviation 0.8	-0.5 mmol/L Standard Deviation 1.0	1.1 mmol/L Standard Deviation 1.2	0.2 mmol/L Standard Deviation 1.9	1.8 mmol/L Standard Deviation 1.50	0.3 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 37	—	—	—	—	—	—	1.5 mmol/L Standard Deviation 2.65	0.0 mmol/L Standard Deviation 1.73
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 57	—	—	—	—	—	—	2.0 mmol/L Standard Deviation 2.45	1.3 mmol/L Standard Deviation 3.21
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 71	—	—	—	—	—	—	1.8 mmol/L Standard Deviation 1.71	1.7 mmol/L Standard Deviation 1.53
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 85	—	—	—	—	—	—	2.0 mmol/L Standard Deviation 2.94	1.5 mmol/L Standard Deviation 3.54
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 91	—	—	—	—	—	—	3.0 mmol/L Standard Deviation 2.83	2.5 mmol/L Standard Deviation 2.12
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Bicarbonate: Change at Day 113	—	—	—	—	—	—	2.3 mmol/L Standard Deviation 1.15	2.7 mmol/L Standard Deviation 2.08
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 2	0.3 mmol/L Standard Deviation 1.0	-1.0 mmol/L Standard Deviation 2.4	0.0 mmol/L Standard Deviation 0.8	1.0 mmol/L Standard Deviation 2.6	-0.3 mmol/L Standard Deviation 1.3	-0.2 mmol/L Standard Deviation 0.9	-0.8 mmol/L Standard Deviation 1.26	1.0 mmol/L Standard Deviation 1.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 3	0.3 mmol/L Standard Deviation 1.3	0.0 mmol/L Standard Deviation 1.8	-1.3 mmol/L Standard Deviation 1.0	1.0 mmol/L Standard Deviation 2.9	-0.1 mmol/L Standard Deviation 1.4	-0.6 mmol/L Standard Deviation 1.2	-0.5 mmol/L Standard Deviation 1.29	-1.0 mmol/L Standard Deviation 2.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 4	-0.8 mmol/L Standard Deviation 0.5	-2.8 mmol/L Standard Deviation 1.9	-1.0 mmol/L Standard Deviation 1.4	-0.5 mmol/L Standard Deviation 2.4	-1.4 mmol/L Standard Deviation 1.8	-0.6 mmol/L Standard Deviation 2.1	0.0 mmol/L Standard Deviation 1.41	-2.0 mmol/L Standard Deviation 1.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 8	3.3 mmol/L Standard Deviation 3.2	0.8 mmol/L Standard Deviation 1.9	0.5 mmol/L Standard Deviation 1.0	1.8 mmol/L Standard Deviation 1.5	0.1 mmol/L Standard Deviation 2.4	0.0 mmol/L Standard Deviation 1.8	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 15	2.3 mmol/L Standard Deviation 0.5	-1.5 mmol/L Standard Deviation 2.6	-0.3 mmol/L Standard Deviation 2.1	0.0 mmol/L Standard Deviation 3.3	—	0.6 mmol/L Standard Deviation 1.7	-1.8 mmol/L Standard Deviation 2.22	0.7 mmol/L Standard Deviation 3.51
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 18	—	—	—	—	1.0 mmol/L Standard Deviation 2.1	-0.5 mmol/L Standard Deviation 1.7	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 22	—	—	—	—	—	—	-1.3 mmol/L Standard Deviation 3.30	0.0 mmol/L Standard Deviation 1.00
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 23	—	—	—	—	—	—	-0.8 mmol/L Standard Deviation 3.50	1.3 mmol/L Standard Deviation 3.06
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 24	—	—	—	—	—	—	-0.5 mmol/L Standard Deviation 3.11	0.7 mmol/L Standard Deviation 5.03
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 29	1.3 mmol/L Standard Deviation 1.9	-0.5 mmol/L Standard Deviation 1.3	0.8 mmol/L Standard Deviation 0.5	0.8 mmol/L Standard Deviation 2.1	-0.4 mmol/L Standard Deviation 2.6	0.6 mmol/L Standard Deviation 1.7	-1.8 mmol/L Standard Deviation 3.30	0.7 mmol/L Standard Deviation 2.89
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 37	—	—	—	—	—	—	-2.0 mmol/L Standard Deviation 1.83	1.7 mmol/L Standard Deviation 4.04
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 57	—	—	—	—	—	—	-0.5 mmol/L Standard Deviation 2.38	1.3 mmol/L Standard Deviation 2.89
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 71	—	—	—	—	—	—	0.8 mmol/L Standard Deviation 1.71	1.0 mmol/L Standard Deviation 1.73
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 85	—	—	—	—	—	—	0.8 mmol/L Standard Deviation 1.71	1.5 mmol/L Standard Deviation 2.12
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 91	—	—	—	—	—	—	-1.0 mmol/L Standard Deviation 1.83	0.5 mmol/L Standard Deviation 0.71
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Chloride: Change at Day 113	—	—	—	—	—	—	0.0 mmol/L Standard Deviation 3.00	-1.7 mmol/L Standard Deviation 1.15
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 15	0.15 mmol/L Standard Deviation 0.49	0.18 mmol/L Standard Deviation 0.44	-0.05 mmol/L Standard Deviation 0.52	-0.08 mmol/L Standard Deviation 0.43	—	-0.04 mmol/L Standard Deviation 0.15	0.10 mmol/L Standard Deviation 0.216	-0.13 mmol/L Standard Deviation 0.231
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 4	-0.20 mmol/L Standard Deviation 0.61	0.13 mmol/L Standard Deviation 0.10	0.03 mmol/L Standard Deviation 0.22	0.50 mmol/L Standard Deviation 0.54	-0.11 mmol/L Standard Deviation 0.52	0.12 mmol/L Standard Deviation 0.32	-0.03 mmol/L Standard Deviation 0.222	0.27 mmol/L Standard Deviation 0.513
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 8	-0.18 mmol/L Standard Deviation 0.56	0.43 mmol/L Standard Deviation 0.48	-0.15 mmol/L Standard Deviation 0.38	0.28 mmol/L Standard Deviation 0.26	-0.23 mmol/L Standard Deviation 0.31	0.03 mmol/L Standard Deviation 0.22	—	—
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 2	0.18 mmol/L Standard Deviation 0.10	0.03 mmol/L Standard Deviation 0.15	0.20 mmol/L Standard Deviation 0.75	0.20 mmol/L Standard Deviation 0.14	-0.10 mmol/L Standard Deviation 0.53	0.11 mmol/L Standard Deviation 0.24	-0.05 mmol/L Standard Deviation 0.191	-0.03 mmol/L Standard Deviation 0.153
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride Potassium: Change at Day 3	-0.08 mmol/L Standard Deviation 0.29	0.15 mmol/L Standard Deviation 0.26	-0.13 mmol/L Standard Deviation 0.43	0.13 mmol/L Standard Deviation 0.15	0.04 mmol/L Standard Deviation 0.57	0.14 mmol/L Standard Deviation 0.39	-0.08 mmol/L Standard Deviation 0.330	0.13 mmol/L Standard Deviation 0.351

SECONDARY outcome

Timeframe: Baseline, Up through Day 29 after a single dose

Population: Safety Set: all enrolled normal healthy volunteer participants who received at least one dose of active drug or placebo. Participants with an evaluable assessment at given time point.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 Participants Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 1: 15 mins post-dose	-0.128 liters Standard Deviation 0.119	0.070 liters Standard Deviation 0.184	-0.015 liters Standard Deviation 0.233	-0.210 liters Standard Deviation 0.175	-0.194 liters Standard Deviation 0.316	-0.103 liters Standard Deviation 0.151	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 1: 60 mins post-dose	-0.175 liters Standard Deviation 0.180	0.175 liters Standard Deviation 0.362	0.015 liters Standard Deviation 0.139	-0.088 liters Standard Deviation 0.138	-0.076 liters Standard Deviation 0.197	-0.074 liters Standard Deviation 0.136	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 1: 120 mins post-dose	-0.033 liters Standard Deviation 0.134	0.180 liters Standard Deviation 0.286	0.180 liters Standard Deviation 0.139	-0.008 liters Standard Deviation 0.017	-0.055 liters Standard Deviation 0.235	-0.045 liters Standard Deviation 0.165	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 2: Pre-dose	-0.033 liters Standard Deviation 0.214	0.170 liters Standard Deviation 0.311	0.138 liters Standard Deviation 0.078	-0.240 liters Standard Deviation 0.189	0.055 liters Standard Deviation 0.243	-0.024 liters Standard Deviation 0.130	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 2: 15 mins post-dose	-0.090 liters Standard Deviation 0.130	0.158 liters Standard Deviation 0.320	0.068 liters Standard Deviation 0.100	-0.285 liters Standard Deviation 0.245	-0.039 liters Standard Deviation 0.290	-0.107 liters Standard Deviation 0.174	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 2: 60 mins post-dose	-0.118 liters Standard Deviation 0.170	0.225 liters Standard Deviation 0.303	0.138 liters Standard Deviation 0.149	-0.275 liters Standard Deviation 0.290	0.003 liters Standard Deviation 0.249	-0.069 liters Standard Deviation 0.125	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 2: 120 mins post-dose	-0.068 liters Standard Deviation 0.194	0.165 liters Standard Deviation 0.289	0.243 liters Standard Deviation 0.131	-0.275 liters Standard Deviation 0.171	0.053 liters Standard Deviation 0.428	-0.015 liters Standard Deviation 0.137	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 3: Pre-dose	0.013 liters Standard Deviation 0.098	0.210 liters Standard Deviation 0.400	0.193 liters Standard Deviation 0.134	-0.158 liters Standard Deviation 0.215	0.113 liters Standard Deviation 0.352	-0.049 liters Standard Deviation 0.104	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 3: 15 mins post-dose	-0.090 liters Standard Deviation 0.156	0.155 liters Standard Deviation 0.324	0.130 liters Standard Deviation 0.107	-0.253 liters Standard Deviation 0.317	-0.028 liters Standard Deviation 0.362	-0.103 liters Standard Deviation 0.139	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 3: 60 mins post-dose	-0.023 liters Standard Deviation 0.159	0.190 liters Standard Deviation 0.322	0.188 liters Standard Deviation 0.164	-0.078 liters Standard Deviation 0.324	0.050 liters Standard Deviation 0.370	-0.068 liters Standard Deviation 0.163	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 3: 120 mins post-dose	0.010 liters Standard Deviation 0.164	0.248 liters Standard Deviation 0.333	0.260 liters Standard Deviation 0.184	-0.065 liters Standard Deviation 0.179	0.088 liters Standard Deviation 0.334	-0.028 liters Standard Deviation 0.167	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 4	-0.093 liters Standard Deviation 0.120	0.253 liters Standard Deviation 0.376	0.293 liters Standard Deviation 0.090	-0.113 liters Standard Deviation 0.185	0.158 liters Standard Deviation 0.339	-0.067 liters Standard Deviation 0.191	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 8	-0.090 liters Standard Deviation 0.136	0.220 liters Standard Deviation 0.411	0.160 liters Standard Deviation 0.193	0.015 liters Standard Deviation 0.232	0.070 liters Standard Deviation 0.277	-0.008 liters Standard Deviation 0.190	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 15	-0.165 liters Standard Deviation 0.299	0.190 liters Standard Deviation 0.306	0.233 liters Standard Deviation 0.079	-0.133 liters Standard Deviation 0.171	—	-0.040 liters Standard Deviation 0.131	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 18	—	—	—	—	0.039 liters Standard Deviation 0.323	-0.408 liters Standard Deviation 0.413	—	—
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers Change at Day 29/end of study (EOS)/end of treatment (ET)	-0.333 liters Standard Deviation 0.252	0.183 liters Standard Deviation 0.336	0.163 liters Standard Deviation 0.112	0.000 liters Standard Deviation 0.182	0.150 liters Standard Deviation 0.241	-0.027 liters Standard Deviation 0.196	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the lower limit of quantitation (LLOQ, 1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers	—	3.33 ng/mL Standard Deviation 1.6	8.37 ng/mL Standard Deviation 0.667	40.5 ng/mL Standard Deviation 16.1	56.7 ng/mL Standard Deviation 23.8	—	—	—

SECONDARY outcome

Timeframe: 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

Population: Participants with CF with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses had plasma concentrations below the LLOQ. One participant had 3 plasma samples with concentrations close to the LLOQ preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Cmax in Participants With CF Cycle 1 (Days 1 to 3)	13.1 mg/mL Standard Deviation 8.9	—	—	—	—	—	—	—
PK of ARO-ENaC: Cmax in Participants With CF Cycle 2 (Days 22 to 24)	9.8 mg/mL Standard Deviation 6.2	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers	—	28 hours Interval 4.0 to 52.0	39 hours Interval 25.0 to 64.0	50 hours Interval 50.0 to 54.0	2 hours Interval 1.0 to 56.0	—	—	—

SECONDARY outcome

Timeframe: 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

Population: Participants with CF with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses had plasma concentrations below the LLOQ. One participant had 3 plasma samples with concentrations close to the LLOQ preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Tmax in Participants With CF Cycle 1 (Days 1 to 3)	25 hours Interval 0.5 to 49.0	—	—	—	—	—	—	—
PK of ARO-ENaC: Tmax in Participants With CF Cycle 2 (Day 22 to 24)	25 hours Interval 0.5 to 49.5	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers	—	11 hours Standard Deviation 1.2	10 hours Standard Deviation 3.6	16 hours Standard Deviation 3.0	10 hours Standard Deviation 0.9	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
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	—	91.7 h·mg/mL Standard Deviation 46.1	247 h·mg/mL Standard Deviation 106	1620 h·mg/mL Standard Deviation 577	1665 h·mg/mL Standard Deviation 650	—	—	—

SECONDARY outcome

Timeframe: 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

Population: Participants with CF with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses had plasma concentrations below the LLOQ. One participant had 3 plasma samples with concentrations close to the LLOQ preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: AUClast in Participants With CF Cycle 1 (Days 1 to 3)	155 h·mg/mL Standard Deviation 34.6	—	—	—	—	—	—	—
PK of ARO-ENaC: AUClast in Participants With CF Cycle 2 (Day 22 to 24)	129 h·mg/mL Standard Deviation 47.7	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers	—	117 h·mg/mL Standard Deviation 43.6	258 h·mg/mL Standard Deviation 145	1762 h·mg/mL Standard Deviation 668	1709 h·mg/mL Standard Deviation 660	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses, all participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 Participants Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers	—	227 L/h Standard Deviation 107	176 L/h Standard Deviation 85	75 L/h Standard Deviation 24	69 L/h Standard Deviation 20	—	—	—

SECONDARY outcome

Timeframe: 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

Population: Participants with CF with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants who received placebo doses had plasma concentrations below the LLOQ. One participant had 3 plasma samples with concentrations close to the LLOQ preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: CL/F in Participants With CF Cycle 1 (Days 1 to 3)	101 L/h Standard Deviation 20	—	—	—	—	—	—	—
PK of ARO-ENaC: CL/F in Participants With CF Cycle 2 (Day 22 to 24)	138 L/h Standard Deviation 46	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers in Cohorts 1-4 with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers	—	8.81 μg Standard Deviation 2.55	22.0 μg Standard Deviation 6.98	69.2 μg Standard Deviation 8.30	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers in Cohorts 1-4 with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers	—	0.134 fraction of study drug Standard Deviation 0.0387	0.176 fraction of study drug Standard Deviation 0.0559	0.225 fraction of study drug Standard Deviation 0.0270	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: Normal healthy volunteers in Cohorts 1-4 with ADS-003 plasma concentration above the LLOQ (1.00 ng/mL). Participants in ARO-ENaC 20 mg cohort, and 1 participant in the 40 mg cohort had plasma concentrations below the LLOQ. One participant in the 180 mg cohort had a single plasma sample, preventing the calculation of PK parameters.

Outcome measures

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 Participants Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=3 Participants Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 Participants with cystic fibrosis received 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 Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers	—	371 mL/h Standard Deviation 262	210 mL/h Standard Deviation 137	129 mL/h Standard Deviation 54	—	—	—	—

Adverse Events

Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Normal Healthy Volunteer Cohort: Pooled Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Cystic Fibrosis Cohort: Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 participants at risk Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 participants at risk Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n=4 participants at risk Participants with cystic fibrosis received 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 n=3 participants at risk Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
Infections and infestations Pneumonia	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Infective pulmonary exacerbation of cystic fibrosis	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113

Other adverse events

Measure	Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 65 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 n=4 participants at risk Normal healthy volunteers received double-blind ARO-ENaC 180 mg on Days 1, 2, 3	Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy n=8 participants at risk Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples before and after dosing.	Normal Healthy Volunteer Cohort: Pooled Placebo n=12 participants at risk Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3	Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 n=4 participants at risk Participants with cystic fibrosis received 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 n=3 participants at risk Participants with cystic fibrosis received double-blind placebo dosed on Days 1, 2, and 3, and Days 22, 23, and 24.
General disorders Fatigue	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
General disorders Feeling hot	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Nervous system disorders Presyncope	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Nervous system disorders Syncope	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
General disorders Chest discomfort	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
General disorders Chest pain	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Nausea	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	16.7% 2/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
General disorders Application site erythema	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	50.0% 2/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Gastrointestinal disorders Dry mouth	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
General disorders Vessel puncture site bruise	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Infections and infestations Respiratory tract infection	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Infections and infestations Staphylococcal infection	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Post procedural discomfort	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	37.5% 3/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Procedural pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 2/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 3/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Sunburn	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Vascular access site bruising	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Injury, poisoning and procedural complications Vascular access site pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	16.7% 2/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Investigations Blood creatinine increased	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Musculoskeletal and connective tissue disorders Ligament sprain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Nervous system disorders Dizziness	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Nervous system disorders Headache	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	50.0% 2/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	50.0% 6/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Nervous system disorders Muscle contractions involuntary	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	8.3% 1/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Reproductive system and breast disorders Heavy menstrual bleeding	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	12.5% 1/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Infective pulmonary exacerbation of cystic fibrosis	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Skin and subcutaneous tissue disorders Dermatitis contact	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	25.0% 1/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/8 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/12 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	0.00% 0/4 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113	33.3% 1/3 • Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113

Additional Information

Chief Operating Officer

Arrowhead Pharmaceuticals, Inc.

Phone: 1 (626) 304-3400

Email: info@arrowheadpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor retains first right to publish results for this multi-center study, and thereafter can review results communications prior to release and can embargo communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication of results but can require removal of its confidential information (excluding results).
• Publication restrictions are in place

Restriction type: OTHER