Safety, Tolerability, and Pharmacokinetic Study of ISIS ApoC-III Rx in Hypertriglyceridemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the dose/response pharmacodynamic effects of ISIS ApoC-III Rx vs. Placebo on fasting total apoC-III levels.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose Response, Phase 2 Study of ISIS 304801 Administered Subcutaneously to Patients With Severe or Uncontrolled Hypertriglyceridemia

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: ISIS apoC-III Rx
* Drug: ISIS apoC-III Rx
* Drug: ISIS apoC-III Rx
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe hypertriglyceridemia Exclusion Criteria: HbA1c >/=9.0%, type 1 diabetes, or history of outpatient insulin use for more than 2 weeks in the last year Body mass index (BMI) >40 kg/m2 History of bariatric surgery or currently on weight loss drugs Use of oral contraceptives or hormone replacement therapy or statins unless stable for 3 months prior to dosing Group 1 and 2 patients: Use of systemic corticosteroids, fibrates, niacin, fish oil or other products containing omega-3 fatty acids within 6 weeks of dosing. Group 3 patients: unable to discontinue use of systemic corticosteroids at least 6 weeks prior to dosing ; use of niacin, fish oil, or other products containing omega-3 fatty acids unless on a stable well controlled dose for at least 30 days prior to screening that is not anticipated to change during the study period. Group 4 patients: unable to discontinue use of systemic corticosteroids at least 6 weeks prior to dosing; use of fibrates niacin, fish oil, or other products containing omega-3 fatty acids unless on a stable well controlled dose for at least 30 days prior to screening that is not anticipated to change during the study period. Use of topical corticosteroids, anticoagulants, or drugs or dietary supplements with potential lipid-altering effects unless dose is stable and well controlled for 30 days prior to dosing Any Screening laboratory values that are out of allowed reference ranges Inability to comply with protocol or study procedures Any other significant illness or condition that may adversely affect the subjects participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Non-extensive PK/non post-prandial | Drug: ISIS apoC-III Rx<br>* Dose 1<br>Drug: ISIS apoC-III Rx<br>* Dose 2<br>Drug: ISIS apoC-III Rx<br>* Dose 3<br>Drug: Placebo<br>* Dose 1<br>Drug: Placebo<br>* Dose 2<br>Drug: Placebo<br>* Dose 3<br>|
| Experimental: Group 2a<br>Extensive PK | Drug: ISIS apoC-III Rx<br>* Dose 1<br>Drug: ISIS apoC-III Rx<br>* Dose 2<br>Drug: ISIS apoC-III Rx<br>* Dose 3<br>Drug: Placebo<br>* Dose 1<br>Drug: Placebo<br>* Dose 2<br>Drug: Placebo<br>* Dose 3<br>|
| Experimental: Group 2b<br>Post-prandial assessment | Drug: ISIS apoC-III Rx<br>* Dose 2<br>Drug: ISIS apoC-III Rx<br>* Dose 3<br>Drug: Placebo<br>* Dose 2<br>Drug: Placebo<br>* Dose 3<br>|
| Experimental: Group 3<br>Stable dose of fibrate | Drug: ISIS apoC-III Rx<br>* Dose 2<br>Drug: ISIS apoC-III Rx<br>* Dose 3<br>Drug: Placebo<br>* Dose 2<br>Drug: Placebo<br>* Dose 3<br>|
| Experimental: Group 4<br>Fredrickson Type 1 dyslipidemia | Drug: ISIS apoC-III Rx<br>* Dose 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VLDL apoC-III | The effect of treatment with ISIS ApoC-III Rx or Placebo on fasting total apoC-III levels. | 92 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertriglyceridemia