A Phase 1/2a Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-HSD in Normal Healthy Volunteers as Well as in Patients With NASH or Suspected NASH
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Arrowhead Pharmaceuticals
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
Study Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of ARO-HSD in healthy adult volunteers and in patients with NASH or suspected NASH.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 19 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Women of child bearing 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
- •On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
- •Normal electrocardiogram (ECG) at Screening
- •No abnormal finding of clinical relevance (other than NASH, suspected NASH in patients) at Screening that could adversely impact subject safety during the study or adversely impact study results.
Exclusion Criteria
- •Clinically significant health concerns (other than NASH, suspected NASH in 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 three months prior to Screening
- •Use of illicit drugs within 1 year prior to Screening, or positive urine drug screen at Screening
- •Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
- •NOTE: additional inclusion/exclusion criteria may apply, per protocol
Arms & Interventions
Cohort 1: ARO-HSD 25 mg
Normal healthy volunteers randomized to double blind ARO-HSD 25 mg on Day 1 only.
Intervention: ARO-HSD Injection (Drug)
Cohort 1: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl) (Drug)
Cohort 2: ARO-HSD 50 mg
Normal healthy volunteers randomized to double blind ARO-HSD 50 mg on Day 1 only.
Intervention: ARO-HSD Injection (Drug)
Cohort 2: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl) (Drug)
Cohort 3: ARO-HSD 100 mg
Normal healthy volunteers randomized to double blind ARO-HSD 100 mg on Day 1 only.
Intervention: ARO-HSD Injection (Drug)
Cohort 3: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl) (Drug)
Cohort 4: ARO-HSD 200 mg
Normal healthy volunteers randomized to double blind ARO-HSD 200 mg on Day 1 only.
Intervention: ARO-HSD Injection (Drug)
Cohort 4: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl) (Drug)
Cohort 1b: ARO-HSD 25 mg
Participants with suspected non-alcoholic steatohepatitis (NASH) receive open-label ARO-HSD 25 mg on Days 1 and 29.
Intervention: ARO-HSD Injection (Drug)
Cohort 3b: ARO-HSD 100 mg
Participants with suspected NASH receive open-label ARO-HSD 100 mg on Days 1 and 29.
Intervention: ARO-HSD Injection (Drug)
Cohort 4b: ARO-HSD 200 mg
Participants with suspected NASH receive open-label ARO-HSD 200 mg on Days 1 and 29.
Intervention: ARO-HSD Injection (Drug)
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
Time Frame: From first dose of study drug through Day 113 (±5 days)
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. 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 Outcomes
- Pharmacokinetics (PK) of ARO-HSD: Plasma Concentrations(Normal Healthy Volunteers: Day 1: 2 hours pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 8, 12, 18, 24; Day 2: 48 hours post-dose, Days 8, 15, 29. NASH Participants: Day 1: 2 hours pre-dose, 30 minutes, 1, 2, 24, hours post-dose, Days 8, 15, 29)
- PK of ARO-HSD in Normal Healthy Volunteers: Maximum Observed Plasma Concentration (Cmax)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- PK of ARO-HSD in Normal Healthy Volunteers: Time to Reach Cmax (Tmax)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- PK of ARO-HSD in Normal Healthy Volunteers: Area Under the Concentration-Time Curve From Dosing (Time 0) to the Time of the Last Measured Concentration (AUClast)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- PK of ARO-HSD in Normal Healthy Volunteers: Terminal Elimination Half-Life (t1/2)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- Secondary: PK of ARO-HSD in Normal Healthy Volunteers: Oral Clearance (CL/F)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- PK of ARO-HSD in Normal Healthy Volunteers: Area Under the Curve From Time 0 to Infinity (AUCinf)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- PK of ARO-HSD in Normal Healthy Volunteers: Apparent Volume of Distribution During the Terminal-Phase (Vz/F)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24, 48 hours postdose)
- Urine PK of ARO-HSD in Normal Healthy Volunteers: Amount of Unchanged Drug Recovered in Urine Over 0-24 Hours Postdose (Ae0-24h)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose)
- Urine PK of ARO-HSD in Normal Healthy Volunteers: Percentage of the Administrated Drug Recovered in Urine Over 0-24 Hours (Fe0-24h)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose)
- Urine PK of ARO-HSD in Normal Healthy Volunteers: Renal Clearance (CLr)(Day 1: Predose, 15 minutes, 30 minutes, 1, 2, 4, 8 12, 18, 24 hours postdose)