Safety, Tolerability, PK, and Pharmacodynamics(PD) of IONIS APOCIII-LRx in Healthy Volunteers With Elevated Triglycerides
May 18, 2018 updated by: Ionis Pharmaceuticals, Inc.
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
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APOC-III-LRx given to healthy volunteer subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
56
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M9L 3A2
- BioPharma Services
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: IONIS-APOC-III-LRx
Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection
|
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
|
Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Up to 183 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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
|
Up to 183 Days
|
|
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
|
Up to 183 days
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
|
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.
|
Up to 183 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Janice Faulknor, BioPharma Services
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 1, 2016
Primary Completion (Actual)
April 30, 2018
Study Completion (Actual)
April 30, 2018
Study Registration Dates
First Submitted
August 23, 2016
First Submitted That Met QC Criteria
September 13, 2016
First Posted (Estimate)
September 14, 2016
Study Record Updates
Last Update Posted (Actual)
May 22, 2018
Last Update Submitted That Met QC Criteria
May 18, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IONIs-ApoCIII-LRx
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