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

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ClinicalTrials.gov Identifier: NCT02900027
Recruitment Status : Completed
First Posted : September 14, 2016
Last Update Posted : May 22, 2018
Sponsor:
Collaborator:
Akcea Therapeutics
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Elevated Triglycerides (TG) Drug: APOC-III-L-Rx Drug: Placebo Comparator Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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
Actual Study Start Date : September 2016
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arms and Interventions
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Arm Intervention/treatment
Experimental: IONIS-APOC-III-LRx
Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection
 Drug: Placebo Comparator
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
Placebo Comparator: Placebo (Normal Saline)
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
 Drug: APOC-III-L-Rx
Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900027


Locations
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Canada, Ontario
BioPharma Services
Toronto, Ontario, Canada, M9L 3A2
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Akcea Therapeutics
Investigators
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Principal Investigator: Janice Faulknor BioPharma Services
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02900027    
Other Study ID Numbers: IONIs-ApoCIII-LRx
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: May 22, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
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Hypertriglyceridemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases