Cystic Fibrosis, Pulmonary
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of single doses of ARO-ENaC in healthy adult volunteers; and to evaluate the safety, tolerability, PK and efficacy of multiple doses of ARO-ENaC in patients with pulmonary cystic fibrosis.
Interventions
DRUGARO-ENaC
single or multiple doses of ARO-ENaC by inhalation of nebulized solution
DRUGPlacebo
calculated volume of normal saline to match active treatment by inhalation of nebulized solution
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception * Willing to provide written informed consent and to comply with study requirements * Normal electrocardiogram (ECG) at Screening * Non-smoking * Normal pulmonary function tests at Screening (NHVs only) * No abnormal finding of clinical relevance at Screening other than CF for CF patients * Confirmed diagnosis of CF based on source verifiable medical record (CF patients only) * All other treatments for CF have been stable for at least 2 months and patient is willing to continue this treatment regimen without change for duration of study (CF patients only)
Exclusion criteria
* Acute lower respiratory infection within 30 days of Screening (NHVs only) * History of asthma (specifically, those subjects at risk of bronchial hyperactivity), anaphylaxis or airway hyper-reactivity * Clinically significant history of hyperkalemia or presence of hyperkalemia at Screening * Clinically significant health concerns (other than CF in CF patients) * Human Immunodeficiency virus (HIV) infection, seropositive for Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV) * Uncontrolled hypertension * Excessive use of alcohol within one month prior to Screening * Use of illicit drugs within 1 year prior to Screening * Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study * CF exacerbation within 30 days of Dosing (CF patients) * History of solid organ transplant (CF patients) * Diagnosis of hepatic cirrhosis (CF patients) Note: additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose | Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Baseline, Up through Day 29 after a single dose |
| Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Cmax in Participants With CF | Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD |
| PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Tmax in Participants With CF | Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD |
| PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) in Normal Healthy Volunteers | 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) |
| Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | 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 |
| PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: CL/F in Participants With CF | Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD |
| PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers | Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5) |
| PK of ARO-ENaC: AUClast in Participants With CF | 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 |
Countries
Australia, New Zealand
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 4 |
| 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 | 4 |
| 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 | 4 |
| 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 | 4 |
| 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. | 8 |
| Normal Healthy Volunteer Cohort: Pooled Placebo Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3 | 12 |
| 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. | 4 |
| 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. | 3 |
| Total | 43 |
Baseline characteristics
| Characteristic | Total | Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Normal Healthy Volunteer Cohort: Pooled Placebo | Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Cystic Fibrosis Cohort: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 12 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 27 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 7 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Female | 23 Participants | 3 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 8 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 20 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 6 Participants | 4 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 8 | 0 / 12 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 3 / 4 | 2 / 4 | 3 / 4 | 3 / 4 | 6 / 8 | 10 / 12 | 3 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 1 / 8 | 0 / 12 | 1 / 4 | 2 / 3 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs)=AEs with onset on or after administration of study drug through end of study. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.
Time frame: 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)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TEAE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 1 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 1 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TEAE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TEAE | 3 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any TEAE | 2 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any TE SAE | 1 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any AE | 6 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any TEAE | 6 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 1 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any TEAE | 8 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any AE | 10 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 5 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any TE SAE | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any TE SAE | 1 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 2 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any TEAE | 3 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 1 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Death | 0 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TE SAE | 0 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any SAE | 2 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Related TEAE | 1 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Drug Withdrawal | 0 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any TEAE | 3 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any AE Resulting in Study Discontinuation | 0 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Cystic Fibrosis Cohort: Placebo | Number of Participants With Adverse Events (AEs) | Any TE SAE | 2 Participants |
Secondary
Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 0.13 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | -0.090 liters | Standard Deviation 0.136 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 0.18 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 15 | -0.165 liters | Standard Deviation 0.299 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | -0.093 liters | Standard Deviation 0.12 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | 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 0.17 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 60 mins post-dose | 0.190 liters | Standard Deviation 0.322 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: Pre-dose | 0.210 liters | Standard Deviation 0.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 15 mins post-dose | 0.155 liters | Standard Deviation 0.324 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 15 mins post-dose | 0.070 liters | Standard Deviation 0.184 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 29/end of study (EOS)/end of treatment (ET) | 0.183 liters | Standard Deviation 0.336 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | 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 0.362 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 120 mins post-dose | 0.180 liters | Standard Deviation 0.286 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 60 mins post-dose | 0.225 liters | Standard Deviation 0.303 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 15 | 0.190 liters | Standard Deviation 0.306 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: Pre-dose | 0.170 liters | Standard Deviation 0.311 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | 0.220 liters | Standard Deviation 0.411 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 15 mins post-dose | 0.158 liters | Standard Deviation 0.32 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | 0.253 liters | Standard Deviation 0.376 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 120 mins post-dose | 0.248 liters | Standard Deviation 0.333 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 120 mins post-dose | 0.165 liters | Standard Deviation 0.289 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 120 mins post-dose | 0.243 liters | Standard Deviation 0.131 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 15 mins post-dose | 0.068 liters | Standard Deviation 0.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 15 | 0.233 liters | Standard Deviation 0.079 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | 0.293 liters | Standard Deviation 0.09 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 15 mins post-dose | 0.130 liters | Standard Deviation 0.107 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 29/end of study (EOS)/end of treatment (ET) | 0.163 liters | Standard Deviation 0.112 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 60 mins post-dose | 0.188 liters | Standard Deviation 0.164 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 60 mins post-dose | 0.015 liters | Standard Deviation 0.139 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 120 mins post-dose | 0.260 liters | Standard Deviation 0.184 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 15 mins post-dose | -0.015 liters | Standard Deviation 0.233 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: Pre-dose | 0.138 liters | Standard Deviation 0.078 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 60 mins post-dose | 0.138 liters | Standard Deviation 0.149 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: Pre-dose | 0.193 liters | Standard Deviation 0.134 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | 0.160 liters | Standard Deviation 0.193 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 120 mins post-dose | 0.180 liters | Standard Deviation 0.139 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 15 mins post-dose | -0.210 liters | Standard Deviation 0.175 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 60 mins post-dose | -0.088 liters | Standard Deviation 0.138 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 120 mins post-dose | -0.008 liters | Standard Deviation 0.017 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: Pre-dose | -0.240 liters | Standard Deviation 0.189 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 15 mins post-dose | -0.285 liters | Standard Deviation 0.245 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 60 mins post-dose | -0.275 liters | Standard Deviation 0.29 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 120 mins post-dose | -0.275 liters | Standard Deviation 0.171 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: Pre-dose | -0.158 liters | Standard Deviation 0.215 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 15 mins post-dose | -0.253 liters | Standard Deviation 0.317 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 60 mins post-dose | -0.078 liters | Standard Deviation 0.324 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 120 mins post-dose | -0.065 liters | Standard Deviation 0.179 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | -0.113 liters | Standard Deviation 0.185 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | 0.015 liters | Standard Deviation 0.232 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 15 | -0.133 liters | Standard Deviation 0.171 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 29/end of study (EOS)/end of treatment (ET) | 0.000 liters | Standard Deviation 0.182 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 60 mins post-dose | -0.076 liters | Standard Deviation 0.197 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 60 mins post-dose | 0.050 liters | Standard Deviation 0.37 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 120 mins post-dose | 0.088 liters | Standard Deviation 0.334 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 60 mins post-dose | 0.003 liters | Standard Deviation 0.249 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 15 mins post-dose | -0.039 liters | Standard Deviation 0.29 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 15 mins post-dose | -0.194 liters | Standard Deviation 0.316 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | 0.158 liters | Standard Deviation 0.339 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: Pre-dose | 0.055 liters | Standard Deviation 0.243 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | 0.070 liters | Standard Deviation 0.277 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 120 mins post-dose | -0.055 liters | Standard Deviation 0.235 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 29/end of study (EOS)/end of treatment (ET) | 0.150 liters | Standard Deviation 0.241 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 18 | 0.039 liters | Standard Deviation 0.323 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 15 mins post-dose | -0.028 liters | Standard Deviation 0.362 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: Pre-dose | 0.113 liters | Standard Deviation 0.352 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 120 mins post-dose | 0.053 liters | Standard Deviation 0.428 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 120 mins post-dose | -0.045 liters | Standard Deviation 0.165 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 29/end of study (EOS)/end of treatment (ET) | -0.027 liters | Standard Deviation 0.196 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: Pre-dose | -0.049 liters | Standard Deviation 0.104 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 60 mins post-dose | -0.068 liters | Standard Deviation 0.163 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 60 mins post-dose | -0.069 liters | Standard Deviation 0.125 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 15 mins post-dose | -0.103 liters | Standard Deviation 0.151 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 8 | -0.008 liters | Standard Deviation 0.19 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 120 mins post-dose | -0.028 liters | Standard Deviation 0.167 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 18 | -0.408 liters | Standard Deviation 0.413 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 15 mins post-dose | -0.107 liters | Standard Deviation 0.174 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 1: 60 mins post-dose | -0.074 liters | Standard Deviation 0.136 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: 120 mins post-dose | -0.015 liters | Standard Deviation 0.137 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 15 | -0.040 liters | Standard Deviation 0.131 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 4 | -0.067 liters | Standard Deviation 0.191 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 2: Pre-dose | -0.024 liters | Standard Deviation 0.13 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | Change at Day 3: 15 mins post-dose | -0.103 liters | Standard Deviation 0.139 |
Secondary
Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride
Time frame: Normal Healthy Volunteers: Baseline, Days 2, 3, 4, 8, 15, 18, 29 ; Participants with CF: Baseline, Days 2, 3, 4, 15, 22, 23. 24, 29, 37, 57, 71, 85, 91, 113
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | -0.5 mmol/L | Standard Deviation 0.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | -1.3 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | -0.3 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | 0.0 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | 2.3 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | -0.08 mmol/L | Standard Deviation 0.29 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 3.3 mmol/L | Standard Deviation 3.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -0.8 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | -0.20 mmol/L | Standard Deviation 0.61 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | 0.3 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | 0.3 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | -0.5 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | -0.18 mmol/L | Standard Deviation 0.56 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | 1.3 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | -0.3 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | 0.15 mmol/L | Standard Deviation 0.49 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | 0.18 mmol/L | Standard Deviation 0.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | -0.8 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | 2.0 mmol/L | Standard Deviation 2.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | -2.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 0.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | -0.5 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | 0.8 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | -0.15 mmol/L | Standard Deviation 0.65 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | -0.5 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | -0.3 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | 0.43 mmol/L | Standard Deviation 0.48 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | 1.3 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | 0.18 mmol/L | Standard Deviation 0.45 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | -0.8 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | 1.0 mmol/L | Standard Deviation 1.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 0.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | 1.3 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | 0.15 mmol/L | Standard Deviation 0.26 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | 0.03 mmol/L | Standard Deviation 0.15 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 0.8 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | 2.5 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -2.8 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | 0.18 mmol/L | Standard Deviation 0.44 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | 0.0 mmol/L | Standard Deviation 1.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | 1.8 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | 0.13 mmol/L | Standard Deviation 0.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | -0.5 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | -1.5 mmol/L | Standard Deviation 2.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | -1.0 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 1.3 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 0.8 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | 0.0 mmol/L | Standard Deviation 2.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | -0.3 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | 0.20 mmol/L | Standard Deviation 0.75 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | -0.13 mmol/L | Standard Deviation 0.43 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | 0.03 mmol/L | Standard Deviation 0.22 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | -0.15 mmol/L | Standard Deviation 0.38 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | -0.05 mmol/L | Standard Deviation 0.52 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | -0.33 mmol/L | Standard Deviation 0.22 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | 0.0 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | -1.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | 0.3 mmol/L | Standard Deviation 2.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | 0.5 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | 0.0 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | -0.3 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 0.5 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | 0.5 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 1.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | -0.3 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | -0.3 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 0.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | 0.0 mmol/L | Standard Deviation 0.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | -1.3 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -1.0 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 0.5 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | 0.8 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | 1.5 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | 1.5 mmol/L | Standard Deviation 3.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | 0.13 mmol/L | Standard Deviation 0.15 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 1.8 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 0.0 mmol/L | Standard Deviation 1.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | 5.0 mmol/L | Standard Deviation 2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | -0.5 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | 1.3 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | 1.5 mmol/L | Standard Deviation 4.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | -1.0 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | -4.8 mmol/L | Standard Deviation 4.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | 0.0 mmol/L | Standard Deviation 3.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | 0.20 mmol/L | Standard Deviation 0.14 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | 0.28 mmol/L | Standard Deviation 0.26 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -0.5 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | -0.5 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | -0.3 mmol/L | Standard Deviation 2.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | -1.0 mmol/L | Standard Deviation 3.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | 0.50 mmol/L | Standard Deviation 0.54 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | -0.08 mmol/L | Standard Deviation 0.43 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | 1.0 mmol/L | Standard Deviation 2.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | 0.8 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | 1.0 mmol/L | Standard Deviation 2.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | 0.05 mmol/L | Standard Deviation 0.17 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -1.4 mmol/L | Standard Deviation 1.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 1.1 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | -0.10 mmol/L | Standard Deviation 0.53 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | 1.9 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | -0.23 mmol/L | Standard Deviation 0.31 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | -0.3 mmol/L | Standard Deviation 1.3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 18 | 1.3 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | -0.11 mmol/L | Standard Deviation 0.52 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 18 | 2.5 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 1.1 mmol/L | Standard Deviation 1.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 18 | 1.0 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | 1.1 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | -0.09 mmol/L | Standard Deviation 0.37 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | 1.8 mmol/L | Standard Deviation 2.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | 0.4 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 0.1 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | -0.4 mmol/L | Standard Deviation 2.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | 0.04 mmol/L | Standard Deviation 0.57 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 0.4 mmol/L | Standard Deviation 1.8 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 18 | -0.16 mmol/L | Standard Deviation 0.5 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | 2.0 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | 0.9 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | -0.1 mmol/L | Standard Deviation 1.4 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | 0.9 mmol/L | Standard Deviation 1 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | 0.8 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 0.2 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 8 | -0.3 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | 0.12 mmol/L | Standard Deviation 0.32 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 18 | -0.5 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 0.2 mmol/L | Standard Deviation 2 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | -0.3 mmol/L | Standard Deviation 1.6 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -0.6 mmol/L | Standard Deviation 2.1 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | -0.6 mmol/L | Standard Deviation 1.6 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 18 | 1.8 mmol/L | Standard Deviation 1.5 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | -1.0 mmol/L | Standard Deviation 1.1 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 18 | 0.20 mmol/L | Standard Deviation 0.27 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | -0.2 mmol/L | Standard Deviation 0.9 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 8 | 0.3 mmol/L | Standard Deviation 1.9 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | -0.04 mmol/L | Standard Deviation 0.15 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | -0.3 mmol/L | Standard Deviation 2.5 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | 0.03 mmol/L | Standard Deviation 0.24 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | 0.6 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 8 | 0.03 mmol/L | Standard Deviation 0.22 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | 0.11 mmol/L | Standard Deviation 0.24 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | 0.6 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | 0.3 mmol/L | Standard Deviation 0.9 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | 0.14 mmol/L | Standard Deviation 0.39 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | 0.6 mmol/L | Standard Deviation 1.7 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 18 | 2.3 mmol/L | Standard Deviation 2.4 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 8 | 0.0 mmol/L | Standard Deviation 1.8 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | -0.3 mmol/L | Standard Deviation 1.6 |
| Normal Healthy Volunteer Cohort: Pooled Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | -0.6 mmol/L | Standard Deviation 1.2 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | -0.5 mmol/L | Standard Deviation 1.91 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | -0.05 mmol/L | Standard Deviation 0.173 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | 1.0 mmol/L | Standard Deviation 2.71 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | 0.5 mmol/L | Standard Deviation 1.73 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | -1.8 mmol/L | Standard Deviation 3.3 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 24 | -0.03 mmol/L | Standard Deviation 0.171 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | -0.5 mmol/L | Standard Deviation 0.58 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 22 | 1.0 mmol/L | Standard Deviation 1.83 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 23 | 1.5 mmol/L | Standard Deviation 2.38 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 24 | 2.0 mmol/L | Standard Deviation 3.92 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 23 | -0.05 mmol/L | Standard Deviation 0.37 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 37 | -2.0 mmol/L | Standard Deviation 1.83 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | -0.5 mmol/L | Standard Deviation 1.91 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 37 | 0.0 mmol/L | Standard Deviation 2.45 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 57 | 0.3 mmol/L | Standard Deviation 2.22 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 71 | 1.3 mmol/L | Standard Deviation 0.5 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 85 | 1.0 mmol/L | Standard Deviation 1.15 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 91 | 1.0 mmol/L | Standard Deviation 1.83 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 113 | -1.0 mmol/L | Standard Deviation 2.65 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 22 | -0.10 mmol/L | Standard Deviation 0.245 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 1.8 mmol/L | Standard Deviation 1.71 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 57 | -0.5 mmol/L | Standard Deviation 2.38 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | -1.0 mmol/L | Standard Deviation 2.16 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | 0.10 mmol/L | Standard Deviation 0.216 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 2.8 mmol/L | Standard Deviation 2.5 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 71 | 0.8 mmol/L | Standard Deviation 1.71 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | 2.0 mmol/L | Standard Deviation 1.41 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 22 | 1.3 mmol/L | Standard Deviation 2.63 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 23 | 1.0 mmol/L | Standard Deviation 1.41 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 24 | 1.3 mmol/L | Standard Deviation 2.22 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | -0.03 mmol/L | Standard Deviation 0.222 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 85 | 0.8 mmol/L | Standard Deviation 1.71 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 1.8 mmol/L | Standard Deviation 1.5 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 37 | 1.5 mmol/L | Standard Deviation 2.65 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 57 | 2.0 mmol/L | Standard Deviation 2.45 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 71 | 1.8 mmol/L | Standard Deviation 1.71 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 85 | 2.0 mmol/L | Standard Deviation 2.94 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 91 | 3.0 mmol/L | Standard Deviation 2.83 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 113 | 2.3 mmol/L | Standard Deviation 1.15 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | -0.8 mmol/L | Standard Deviation 1.26 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 91 | -1.0 mmol/L | Standard Deviation 1.83 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | -0.5 mmol/L | Standard Deviation 1.29 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | -0.08 mmol/L | Standard Deviation 0.33 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | 0.0 mmol/L | Standard Deviation 1.41 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 113 | 0.0 mmol/L | Standard Deviation 3 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | -0.05 mmol/L | Standard Deviation 0.191 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | -1.8 mmol/L | Standard Deviation 2.22 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 22 | -1.3 mmol/L | Standard Deviation 3.3 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 23 | -0.8 mmol/L | Standard Deviation 3.5 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 24 | -0.5 mmol/L | Standard Deviation 3.11 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 57 | -0.05 mmol/L | Standard Deviation 0.311 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 71 | 0.03 mmol/L | Standard Deviation 0.275 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 85 | 0.10 mmol/L | Standard Deviation 0.356 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 91 | 0.03 mmol/L | Standard Deviation 0.403 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 113 | -0.03 mmol/L | Standard Deviation 0.321 |
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 37 | 0.13 mmol/L | Standard Deviation 0.33 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 3 | 0.13 mmol/L | Standard Deviation 0.351 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 57 | -0.10 mmol/L | Standard Deviation 0.2 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 57 | 1.3 mmol/L | Standard Deviation 2.89 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 3 | 0.7 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 15 | -0.13 mmol/L | Standard Deviation 0.231 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 24 | 0.07 mmol/L | Standard Deviation 0.321 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 3 | -1.0 mmol/L | Standard Deviation 2 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 71 | 0.10 mmol/L | Standard Deviation 0.265 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 2 | 0.7 mmol/L | Standard Deviation 3.79 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 91 | 0.5 mmol/L | Standard Deviation 0.71 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 37 | 1.7 mmol/L | Standard Deviation 4.04 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 113 | -2.0 mmol/L | Standard Deviation 1 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 91 | 0.0 mmol/L | Standard Deviation 1.41 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 4 | -0.7 mmol/L | Standard Deviation 2.52 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 4 | -2.0 mmol/L | Standard Deviation 1 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 85 | 0.0 mmol/L | Standard Deviation 1.41 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 71 | -0.3 mmol/L | Standard Deviation 0.58 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 85 | -0.25 mmol/L | Standard Deviation 0.071 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 57 | -1.3 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 37 | -0.7 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 29 | 0.0 mmol/L | Standard Deviation 1 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 2 | -0.03 mmol/L | Standard Deviation 0.153 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 3 | 0.3 mmol/L | Standard Deviation 4.04 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 22 | -0.27 mmol/L | Standard Deviation 0.306 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 24 | 1.3 mmol/L | Standard Deviation 5.77 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 23 | 0.7 mmol/L | Standard Deviation 3.79 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 91 | -0.10 mmol/L | Standard Deviation 0.283 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 15 | 0.7 mmol/L | Standard Deviation 3.51 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 22 | 0.3 mmol/L | Standard Deviation 3.21 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 15 | -1.3 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 29 | 0.00 mmol/L | Standard Deviation 0.3 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 22 | 0.0 mmol/L | Standard Deviation 1 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 4 | 0.27 mmol/L | Standard Deviation 0.513 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 113 | 0.07 mmol/L | Standard Deviation 0.153 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 29 | 0.3 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 23 | 1.3 mmol/L | Standard Deviation 3.06 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 37 | 0.0 mmol/L | Standard Deviation 1.73 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 37 | 0.07 mmol/L | Standard Deviation 0.404 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 57 | 1.3 mmol/L | Standard Deviation 3.21 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 24 | 0.7 mmol/L | Standard Deviation 5.03 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 71 | 1.7 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 29 | 0.7 mmol/L | Standard Deviation 2.89 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 85 | 1.5 mmol/L | Standard Deviation 3.54 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Potassium: Change at Day 23 | -0.07 mmol/L | Standard Deviation 0.153 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 91 | 2.5 mmol/L | Standard Deviation 2.12 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 113 | -1.7 mmol/L | Standard Deviation 1.15 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 113 | 2.7 mmol/L | Standard Deviation 2.08 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 24 | -1.3 mmol/L | Standard Deviation 5.13 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 23 | 0.7 mmol/L | Standard Deviation 0.58 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 85 | 1.5 mmol/L | Standard Deviation 2.12 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 22 | 0.3 mmol/L | Standard Deviation 1.53 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 15 | 0.7 mmol/L | Standard Deviation 3.21 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 71 | 1.0 mmol/L | Standard Deviation 1.73 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Sodium: Change at Day 2 | -1.3 mmol/L | Standard Deviation 0.58 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Chloride: Change at Day 2 | 1.0 mmol/L | Standard Deviation 1 |
| Cystic Fibrosis Cohort: Placebo | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Bicarbonate: Change at Day 4 | 1.3 mmol/L | Standard Deviation 1.53 |
Secondary
Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | 3.33 ng/mL | Standard Deviation 1.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | 8.37 ng/mL | Standard Deviation 0.667 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | 40.5 ng/mL | Standard Deviation 16.1 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | 56.7 ng/mL | Standard Deviation 23.8 |
Secondary
PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers | 22.0 μg | Standard Deviation 6.98 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers | 69.2 μg | Standard Deviation 8.3 |
Secondary
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers | 258 h·mg/mL | Standard Deviation 145 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers | 1762 h·mg/mL | Standard Deviation 668 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers | 1709 h·mg/mL | Standard Deviation 660 |
Secondary
PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | 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 | 247 h·mg/mL | Standard Deviation 106 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | 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 | 1620 h·mg/mL | Standard Deviation 577 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | 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 | 1665 h·mg/mL | Standard Deviation 650 |
Secondary
PK of ARO-ENaC: AUClast in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: AUClast in Participants With CF | Cycle 1 (Days 1 to 3) | 155 h·mg/mL | Standard Deviation 34.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: AUClast in Participants With CF | Cycle 2 (Day 22 to 24) | 129 h·mg/mL | Standard Deviation 47.7 |
Secondary
PK of ARO-ENaC: CL/F in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: CL/F in Participants With CF | Cycle 1 (Days 1 to 3) | 101 L/h | Standard Deviation 20 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: CL/F in Participants With CF | Cycle 2 (Day 22 to 24) | 138 L/h | Standard Deviation 46 |
Secondary
PK of ARO-ENaC: Cmax in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: Cmax in Participants With CF | Cycle 1 (Days 1 to 3) | 13.1 mg/mL | Standard Deviation 8.9 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: Cmax in Participants With CF | Cycle 2 (Days 22 to 24) | 9.8 mg/mL | Standard Deviation 6.2 |
Secondary
PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | 11 hours | Standard Deviation 1.2 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | 10 hours | Standard Deviation 3.6 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | 16 hours | Standard Deviation 3 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | 10 hours | Standard Deviation 0.9 |
Secondary
PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | 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 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers | 0.176 fraction of study drug | Standard Deviation 0.0559 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers | 0.225 fraction of study drug | Standard Deviation 0.027 |
Secondary
PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | 227 L/h | Standard Deviation 107 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | 176 L/h | Standard Deviation 85 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | 75 L/h | Standard Deviation 24 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | 69 L/h | Standard Deviation 20 |
Secondary
PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers | 371 mL/h | Standard Deviation 262 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers | 210 mL/h | Standard Deviation 137 |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers | 129 mL/h | Standard Deviation 54 |
Secondary
PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers
Time frame: Day 1: Pre-dose, 30, 60, 120 mins and 4, 6, 8, 16 hours post-inhalation; Day 2: Pre-dose (Day 1, 24-hour timepoint), then 1, 2, 4 hours post-inhalation; Day 3: (Day 2, 24 hour timepoint), 30, 60, 120 mins, 4, 6, 8, 16, 24 (On Day 4), 48 (on Day 5)
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | 28 hours |
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | 39 hours |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | 50 hours |
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | 2 hours |
Secondary
PK of ARO-ENaC: Tmax in Participants With CF
Time frame: Cycle 1 Day 1: Pre-dose (PrD), 30, 60, 120 minutes (m), 4 hours (h) post-dose (PoD); Day 2: PrD, 60, 120 m, 4 h PoD; Day 3: PrD, 30, 60, 120 m, 4 h PoD. Cycle 2 Days 22 and 23: PrD, 30 m, 4 h PoD; Day 24: PrD, 30, 60, 120 m, 4 h PoD
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: Tmax in Participants With CF | Cycle 1 (Days 1 to 3) | 25 hours |
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | PK of ARO-ENaC: Tmax in Participants With CF | Cycle 2 (Day 22 to 24) | 25 hours |