Clinical trial NCT02900027: Safety, Tolerability, PK, and Pharmacodynamics(PD) of IONIS APOCIII-LRx in Healthy Volunteers With Elevated Triglycerides
Official title: Placebo-Controlled, Dose-Escalation Study to Assess Safety, Tolerability, PK and PD of a GalNAc3 Conjugated Antisense Oligonucleotide Targeting ApoC-III, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Elevated Triglycerides (TG)
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Akcea Therapeutics
First posted: 2016-09-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APOC-III-LRx given to healthy volunteer subjects.


Eligibility criteria: Inclusion Criteria:

* Must have given written informed consent and be able to comply with all study requirements
* Healthy males or females aged 18-65 inclusive
* Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal
* Males must be surgically sterile, abstinent or using an acceptable contraceptive method
* BMI \< 35.0 kg/m2
* Subjects must have Fasting TG ≥ 90 mg/dL or ≥ 200 mg/dL depending on Cohort assignment

Exclusion Criteria:

* Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
* Treatment with another Study Drug, biological agent, or device within one-month of screening
* Regular excessive use of alcohol within 6 months of Screening
* Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
* Smoking \> 10 cigarettes a day
* Considered unsuitable for inclusion by the Principal Investigator

Primary outcomes:
measure: To evaluate the safety and tolerability of single and multiple doses of IONIS- APOC-III-LRx - (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
timeFrame: Up to 183 days
Secondary outcomes:
measure: To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
timeFrame: Up to 183 days
measure: To evaluate the urine pharmacokinetics of single and multiple doses of IONIS¬-APOC-III-LRx
timeFrame: Up to 183 days
measure: To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
timeFrame: Up to 183 Days
measure: To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
timeFrame: Up to 183 days
Other outcomes:
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
measure: Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx
timeFrame: Up to 183 days
Locations:
city: Toronto
country: Canada
facility: BioPharma Services
state: Ontario
Study officials:
affiliation: BioPharma Services
name: Janice Faulknor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alexander VJ, Xia S, Hurh E, Hughes SG, O'Dea L, Geary RS, Witztum JL, Tsimikas S. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019 Sep 1;40(33):2785-2796. doi: 10.1093/eurheartj/ehz209.