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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hypertriglyceridemia

Treatments: Drug: Placebo; Drug: ISIS apoC-III Rx

Study type: Interventional

Funder types: Industry

Identifiers

NCT01529424

ISIS 304801-CS2

Details and patient eligibility

About

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.

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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89 participants in 5 patient groups

Group 1

Experimental group

Description:

Non-extensive PK/non post-prandial

Treatment:

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: Placebo

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: ISIS apoC-III Rx

Group 2a

Experimental group

Description:

Extensive PK

Treatment:

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: Placebo

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: ISIS apoC-III Rx

Group 2b

Experimental group

Description:

Post-prandial assessment

Treatment:

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: Placebo

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: ISIS apoC-III Rx

Group 3

Experimental group

Description:

Stable dose of fibrate

Treatment:

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: Placebo

Drug: ISIS apoC-III Rx

Drug: Placebo

Drug: ISIS apoC-III Rx

Group 4

Experimental group

Description:

Fredrickson Type 1 dyslipidemia

Treatment:

Drug: ISIS apoC-III Rx

Drug: ISIS apoC-III Rx

Drug: ISIS apoC-III Rx