Clinical trial NCT03783377: Study of ARO-APOC3 in Healthy Volunteers, Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome (FCS)
Official title: A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertriglyceridemia
Familial Chylomicronemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-12-21
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).


Eligibility criteria: 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
* Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS

Exclusion Criteria:

* Clinically significant health concerns
* Regular use of alcohol within one month prior to Screening
* Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
* Recent use of illicit drugs
* Use of more than two tobacco/nicotine containing or cannabis products per month within 6 months prior to drug administration (applicable only to Normal Healthy Volunteers)

Note: additional inclusion/exclusion criteria may apply, per protocol

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
timeFrame: Up to Day 113 (+/- 3 days)
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-APOC3 in Normal Healthy Volunteers (NHVs): Maximum Observed Plasma Concentration (Cmax)
timeFrame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Terminal Elimination Half-Life (t1/2)
timeFrame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
timeFrame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
timeFrame: Single dose phase: Up to 48 hours post-dose
measure: Reduction in Fasting Serum APOC3 from Pre-Dose Baseline
timeFrame: Up to Day 113 (+/- 3 days)
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast Clinical Trial Centre
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Institute de Recherches Cliniques de Montreal
state: Quebec
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Limited
state: Auckland
city: Papatoetoe
country: New Zealand
facility: Middlemore Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Lipid & Diabetes Research Group
Study officials:
References: