Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
- Conditions
- Familial HypercholesterolemiaHypertriglyceridemia
- Interventions
- Drug: IONIS ANGPTL3-LRxDrug: Placebo
- Registration Number
- NCT02709850
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS ANGPTL3-LRx (ISIS 703802) given to healthy volunteer subjects with elevated triglycerides and subjects with familial hypercholesterolemia.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohorts A, D: IONIS ANGPTL3-LRx 120 mg IONIS ANGPTL3-LRx Participants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1. Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg IONIS ANGPTL3-LRx Participants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks. Cohorts B, C: Placebo Placebo Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1. Cohorts B, C: IONIS ANGPTL3-LRx 40 mg IONIS ANGPTL3-LRx Participants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1. Cohorts B, C: IONIS ANGPTL3-LRx 80 mg IONIS ANGPTL3-LRx Participants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1. Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg IONIS ANGPTL3-LRx Participants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks. Cohorts A, D: Placebo Placebo Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1. Cohorts AA-DD: Placebo Placebo Participants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks. Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg IONIS ANGPTL3-LRx Participants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks. Cohorts A, D: IONIS ANGPTL3-LRx 20 mg IONIS ANGPTL3-LRx Participants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1. Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg IONIS ANGPTL3-LRx Participants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.
- Primary Outcome Measures
Name Time Method Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels) Up to Day 127 Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline.
Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters) Up to Day 127 The safety and tolerability of IONIS ANGPTL3-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS ANGPTL3-LRx will be compared with those from subjects dosed with placebo.
Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx. Up to Day 127 The plasma pharmacokinetics (concentration-time results) of IONIS ANGPTL3-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of IONIS ANGPTL3-LRx excreted in urine at selected 24-hour intervals will also be determined.
- Secondary Outcome Measures
Name Time Method Pharmacodynamic effects of IONIS ANGPTL3-LRx Up to Day 127 Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline.
Trial Locations
- Locations (1)
Clinical Site
🇨🇦Toronto, Ontario, Canada