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
Overview
- Phase
- Phase 1
- Intervention
- ARO-HSD Injection
- Conditions
- Non-alcoholic Steatohepatitis
- Sponsor
- Arrowhead Pharmaceuticals
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
- Status
- Completed
- Last Updated
- 7 months ago
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.
Investigators
Eligibility Criteria
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
Cohort 1: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl)
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
Cohort 2: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl)
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
Cohort 3: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl)
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
Cohort 4: Placebo
Normal healthy volunteers randomized to double blind placebo on Day 1 only.
Intervention: sterile normal saline (0.9% NaCl)
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
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
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
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)