A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis
Overview
- Phase
- Phase 1
- Intervention
- IONIS-ENaCRx
- Conditions
- Healthy Subjects
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 98
- Locations
- 8
- Primary Endpoint
- Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This Phase 1/2a study is a double-blinded (subject and Investigator), randomized, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple nebulized doses of IONIS-ENaCRx.
Detailed Description
This study will be conducted in 3 parts: a single ascending dose (SAD) leading to a multiple ascending dose (MAD) in healthy volunteers, followed by a MAD in patients with cystic fibrosis. The study will enroll up to 88 participants. The study will consist of 4 single-dose randomized cohorts. Participants enrolled will receive a single inhaled dose of the Study Drug (IONIS-ENaCRx or placebo) on Day 1.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
IONIS-ENaCRx
Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.
Intervention: IONIS-ENaCRx
Placebo
Placebo comparator calculated volume to match active comparator inhaled or nebulized.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event
Time Frame: Up to 113 Days
Secondary Outcomes
- Tmax: time taken to reach maximal concentration in plasma of IONIS-ENaCRx(Up to 113 Days)
- CL/F: apparent total clearance of IONIS-ENaCRx(Up to 113 Days)
- Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx(Up to 113 Days)
- t1/2λz: termination half-life of IONIS-ENaCRx(Up to 113 Days)
- AUCt: area under the plasma concentration-time curve from time zero to time t for IONIS-ENaCRx(Up to 113 Days)
- The amount of administered dose of IONIS-ENaCRx excreted in urine over a 24-hour period(Up to 113 Days)