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Completed

NCT Number: NCT02900027

Safety, Tolerability, PK, and Pharmacodynamics(PD) of IONIS APOCIII-LRx in Healthy Volunteers With Elevated Triglycerides

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

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Key information

Conditions

Elevated Triglycerides (TG) Dyslipidemias Hyperlipidemias Hypertriglyceridemia Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

BioPharma Services

Toronto, Ontario, M9L 3A2, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

APOC-III-L-Rx

Drug

Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection

placebo comparator

Drug

Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator

Primary outcomes

  1. 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)

    Time frame: Up to 183 days

    The safety and tolerability of IONIS- APOC-III-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 APOC-III-LRx will be compared with those from subjects dosed with placebo.

Secondary outcomes

  1. To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx

    Time frame: Up to 183 days

    The maximum area under the curve (AUC) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration

  2. To evaluate the urine pharmacokinetics of single and multiple doses of IONIS¬-APOC-III-LRx

    Time frame: Up to 183 days

    The amount of IONIS-APOC-III-LRx excreted in urine at selected 24-hour intervals [Ae0-24h] will be determined.

  3. To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx

    Time frame: Up to 183 Days

    The maximum plasma concentration (Cmax) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration

  4. To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx

    Time frame: Up to 183 days

    The maximum time to Cmax (Tmax) of IONIS- APOC-III-LRx will be assessed following single and multiple-dose SC administration

Other outcomes

  1. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with plasma apolipoprotein C-III (apoC-III) compared to baseline.

  2. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with TG compared to baseline.

  3. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with total cholesterol (TC) compared to baseline.

  4. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with low density lipoprotein cholesterol (LDL-C) compared to baseline.

  5. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with high density lipoprotein cholesterol (HDL-C) compared to baseline.

  6. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with non-high density lipoprotein cholesterol (non-HDL-C) compared to baseline.

  7. Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx

    Time frame: Up to 183 days

    Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with very low density lipoprotein cholesterol (VLDL-C) compared to baseline.

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Collaborators

  • Akcea Therapeutics

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Sep 14, 2016
Registry last updated
May 22, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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