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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal Healthy Volunteer Cohort: ARO-ENaC 20 mg, Days 1-3 | Experimental | Normal healthy volunteers receive double-blind ARO-ENaC 20 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 20 mg, Days 1-3 | Placebo Comparator | Normal healthy volunteers receive double-blind placebo for ARO-ENaC 20 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 | Experimental | Normal healthy volunteers receive double-blind ARO-ENaC 40 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 40 mg, Days 1-3 | Placebo Comparator | Normal healthy volunteers receive double-blind placebo for ARO-ENaC 40 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: ARO-ENaC 65 mg, Days 1-3 | Experimental | Normal healthy volunteers receive double-blind ARO-ENaC 65 mg on Days 1, 2, 3 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARO-ENaC | Drug | single or multiple doses of ARO-ENaC by inhalation of nebulized solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers |
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Inclusion Criteria:
Exclusion Criteria:
Note: additional inclusion/exclusion criteria may apply per protocol
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site 3 | Chermside | Queensland | 4032 | Australia | ||
| Research Site 4 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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. |
| FG005 | Normal Healthy Volunteer Cohort: Pooled Placebo | Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3 |
| FG006 | 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. |
| FG007 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Normal Healthy Volunteer Cohort: ARO-ENaC 40 mg, Days 1-3 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Set (all enrolled participants who received at least one dose of active drug or placebo) | Posted | Count of Participants | Participants | No | Normal Healthy Volunteers: Up to 29 (+/- 2) days post-dose; Participants with cystic fibrosis (CF): Up to 113 (+/- 5) days post-dose |
|
Normal Healthy Volunteers: From Screening up to Day 29 ; CF Participants: From Screening up to Day 113
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
On 01 July 2021 a voluntary suspension of dosing by the Sponsor was initiated. All subjects who had completed all planned doses continued safety follow-up according to the scheduled activities. This suspension of dosing was due to preliminary findings in the 6-month chronic rat good laboratory practice (GLP) toxicology study. The voluntary suspension was unrelated to any safety findings in the AROENaC1001 study. Subsequent to this, the Sponsor decided to terminate the AROENaC1001 study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Operating Officer | Arrowhead Pharmaceuticals, Inc. | 1 (626) 304-3400 | info@arrowheadpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 9, 2021 | Aug 3, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 17, 2021 | Aug 3, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 65 mg, Days 1-3 |
| Placebo Comparator |
Normal healthy volunteers receive double-blind placebo for ARO-ENaC 65 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 | Experimental | Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 | Placebo Comparator | Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 |
|
| Normal Healthy Volunteer Cohort: ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Experimental | Normal healthy volunteers receive double-blind ARO-ENaC 180 mg on Days 1, 2, 3 with the purpose of collecting bronchoscopic samples |
|
| Normal Healthy Volunteer Cohort: Placebo for ARO-ENaC 180 mg, Days 1-3 With Bronchoscopy | Placebo Comparator | Normal healthy volunteers receive double-blind placebo for ARO-ENaC 180 mg on Days 1, 2, 3 to collect bronchoscopic samples |
|
| Cystic Fibrosis Cohort: ARO-ENaC 40 mg, Days 1-3, 22-24 | Experimental | Participants with cystic fibrosis receive double-blind ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and 40 mg dosed on Days 22, 23, and 24 |
|
| Cystic Fibrosis Cohort: Placebo | Placebo Comparator | Participants with cystic fibrosis receive double-blind placebo for ARO-ENaC 40 mg dosed on Days 1, 2, and 3, and Days 22, 23, and 24. |
|
| Placebo | Drug | calculated volume of normal saline to match active treatment by inhalation of nebulized solution |
|
| 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) |
| 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 |
| 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) |
| South Brisbane |
| Queensland |
| 4101 |
| Australia |
| Research Site 1 | Nedlands | Washington | 6009 | Australia |
| Research Site 2 | Hamilton | 3204 | Australia |
| Research Site 6 | Grafton | Auckland | 1010 | New Zealand |
| Research Site 8 | Christchurch | 8140 | New Zealand |
| Research Site 7 | Dunedin | 9054 | New Zealand |
Normal healthy volunteers received double-blind ARO-ENaC 40 mg on Days 1, 2, 3
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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. |
| BG005 | Normal Healthy Volunteer Cohort: Pooled Placebo | Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3 |
| BG006 | 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. |
| BG007 | 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. |
| BG008 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
Normal healthy volunteers received double-blind ARO-ENaC 20 mg on Days 1, 2, 3 |
| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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. |
| OG005 | Normal Healthy Volunteer Cohort: Pooled Placebo | Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3 |
| OG006 | 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. |
| OG007 | 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. |
|
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| Secondary | Change From Baseline in Serum Electrolytes: Potassium, Sodium, Bicarbonate and Chloride | Safety Set: all enrolled participants who received at least one dose of active drug or placebo. Participants with an assessment at given time point. | Posted | Mean | Standard Deviation | mmol/L | 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 |
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| Secondary | Change From Baseline in Forced Expiratory Volume (FEV1) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | liters | Baseline, Up through Day 29 after a single dose |
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| Secondary | Pharmacokinetics (PK) of ARO-ENaC: Maximum Observed Plasma Concentration (Cmax) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | ng/mL | 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) |
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| Secondary | PK of ARO-ENaC: Cmax in Participants With CF | 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. | Posted | Mean | Standard Deviation | mg/mL | 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 |
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| Secondary | PK of ARO-ENaC: Time to Maximum Plasma Concentration (Tmax) in Normal Healthy Volunteers | 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. | Posted | Median | Full Range | hours | 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) |
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| Secondary | PK of ARO-ENaC: Tmax in Participants With CF | 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. | Posted | Median | Full Range | hours | 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 |
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| Secondary | PK of ARO-ENaC: Elimination Half-Life (t1/2) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | hours | 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) |
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| 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 | 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. | Posted | Mean | Standard Deviation | h·mg/mL | 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) |
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| Secondary | PK of ARO-ENaC: AUClast in Participants With CF | 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. | Posted | Mean | Standard Deviation | h·mg/mL | 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 |
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| Secondary | PK of ARO-ENaC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | h·mg/mL | 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) |
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| Secondary | PK of ARO-ENaC: Plasma Clearance (CL/F) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | L/h | 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) |
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| Secondary | PK of ARO-ENaC: CL/F in Participants With CF | 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. | Posted | Mean | Standard Deviation | L/h | 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 |
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| Secondary | PK of ARO-ENaC: Amount Recovered in Urine Over 0 to 24 Hours Postdose (Ae0-24h) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | μg | 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) |
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| Secondary | PK of ARO-ENaC: Fraction Excreted in Urine as Unchanged Drug Over 0 to 24 Hours Postdose (fe0-24h) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | fraction of study drug | 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) |
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| Secondary | PK of ARO-ENaC: Renal Clearance (CLR) in Normal Healthy Volunteers | 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. | Posted | Mean | Standard Deviation | mL/h | 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) |
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| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | 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 | 0 | 4 | 0 | 4 | 2 | 4 |
| EG002 | 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 | 0 | 4 | 0 | 4 | 3 | 4 |
| EG003 | 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 | 0 | 4 | 0 | 4 | 3 | 4 |
| EG004 | 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. | 0 | 8 | 1 | 8 | 6 | 8 |
| EG005 | Normal Healthy Volunteer Cohort: Pooled Placebo | Normal healthy volunteers received double-blind sterile normal saline (0.9% NaCl) on Days 1, 2, 3 | 0 | 12 | 0 | 12 | 10 | 12 |
| EG006 | 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. | 0 | 4 | 1 | 4 | 3 | 4 |
| EG007 | 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. | 0 | 3 | 2 | 3 | 3 | 3 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Application site erythema | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Post procedural fever | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Vascular access site bruising | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Vascular access site pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Ligament sprain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Muscle contractions involuntary | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Heavy menstrual bleeding | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Sinus pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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The only disclosure restriction on the PI is that the sponsor retains first right to publish results for this multi-center study, and thereafter can review results communications prior to release and can embargo communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication of results but can require removal of its confidential information (excluding results).
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| Potassium: Change at Day 3 |
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| Potassium: Change at Day 4 |
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| Potassium: Change at Day 8 |
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| Potassium: Change at Day 15 |
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| Potassium: Change at Day 18 |
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| Potassium: Change at Day 22 |
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| Potassium: Change at Day 23 |
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| Potassium: Change at Day 24 |
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| Potassium: Change at Day 29 |
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| Potassium: Change at Day 37 |
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| Potassium: Change at Day 57 |
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| Potassium: Change at Day 71 |
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| Potassium: Change at Day 85 |
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| Potassium: Change at Day 91 |
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| Potassium: Change at Day 113 |
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| Sodium: Change at Day 2 |
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| Sodium: Change at Day 3 |
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| Sodium: Change at Day 4 |
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| Sodium: Change at Day 8 |
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| Sodium: Change at Day 15 |
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| Sodium: Change at Day 18 |
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| Sodium: Change at Day 22 |
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| Sodium: Change at Day 23 |
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| Sodium: Change at Day 24 |
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| Sodium: Change at Day 29 |
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| Sodium: Change at Day 37 |
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| Sodium: Change at Day 57 |
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| Sodium: Change at Day 71 |
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| Sodium: Change at Day 85 |
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| Sodium: Change at Day 91 |
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| Sodium: Change at Day 113 |
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| Bicarbonate: Change at Day 2 |
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| Bicarbonate: Change at Day 3 |
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| Bicarbonate: Change at Day 4 |
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| Bicarbonate: Change at Day 8 |
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| Bicarbonate: Change at Day 15 |
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| Bicarbonate: Change at Day 18 |
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| Bicarbonate: Change at Day 22 |
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| Bicarbonate: Change at Day 23 |
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| Bicarbonate: Change at Day 24 |
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| Bicarbonate: Change at Day 29 |
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| Bicarbonate: Change at Day 37 |
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| Bicarbonate: Change at Day 57 |
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| Bicarbonate: Change at Day 71 |
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| Bicarbonate: Change at Day 85 |
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| Bicarbonate: Change at Day 91 |
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| Bicarbonate: Change at Day 113 |
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| Chloride: Change at Day 2 |
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| Chloride: Change at Day 3 |
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| Chloride: Change at Day 4 |
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| Chloride: Change at Day 8 |
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| Chloride: Change at Day 15 |
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| Chloride: Change at Day 18 |
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| Chloride: Change at Day 22 |
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| Chloride: Change at Day 23 |
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| Chloride: Change at Day 24 |
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| Chloride: Change at Day 29 |
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| Chloride: Change at Day 37 |
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| Chloride: Change at Day 57 |
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| Chloride: Change at Day 71 |
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| Chloride: Change at Day 85 |
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| Chloride: Change at Day 91 |
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| Chloride: Change at Day 113 |
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| Change at Day 1: 60 mins post-dose |
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| Change at Day 1: 120 mins post-dose |
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| Change at Day 2: Pre-dose |
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| Change at Day 2: 15 mins post-dose |
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| Change at Day 2: 60 mins post-dose |
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| Change at Day 2: 120 mins post-dose |
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| Change at Day 3: Pre-dose |
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| Change at Day 3: 15 mins post-dose |
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| Change at Day 3: 60 mins post-dose |
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| Change at Day 3: 120 mins post-dose |
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| Change at Day 4 |
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| Change at Day 8 |
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| Change at Day 15 |
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| Change at Day 18 |
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| Change at Day 29/end of study (EOS)/end of treatment (ET) |
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