Clinical trial NCT00231569: Dose-escalating Safety Study in Subjects on Stable Statin Therapy
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety and Pharmacodynamics of ISIS 301012 in Hypercholesterolemic Subjects on Stable Statin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: LDL-cholesterol
apoB-100
apoB-48
Lead sponsor: Kastle Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2005-10-04
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.


Eligibility criteria: Inclusion Criteria:

* On a stable dose of \>/= 40 mg Simvastatin or atorvastatin daily for \>/= 3 months prior to baseline and expected to remain on this dose for the remainder of the study
* LDL-cholesterol between 2.60 and 5.70 mmol/L (100 and 220 mg/dL), inclusive at screening
* Females not of childbearing potential.

Exclusion Criteria:

* History of CHD or CHD-equivalent (such as diabetes mellitus, or another clinical form of atherosclerotic disease, e.g., peripheral arterial disease, abdominal aortic aneurysm, or symptomatic carotid artery disease)
* Fasting triglyceride \>2.26 mmol/L (200 mg/dL) at screening
* Any uncontrolled medical/surgical/psychiatric condition, including conditions that may predispose to secondary hypercholesterolemia
* Current diagnosis or known history of complement deficiency or abnormality
* A positive hepatitis B surface antigen or hepatitis C antibody, or a known positive HIV status
* Current diagnosis or known history of liver disease, or has an ALT \>ULN at screening
* Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or has a CPK \>ULN at screening
* Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been adequately treated
* The advisability of a subject taking any prescription medication (apart from simvastatin or atorvastatin) within 6 weeks prior to screening should be discussed with the Isis Medical Monitor
* Subject unwilling to discontinue taking alternative/herbal medication for the duration of the study
* History of drug abuse within 2 years of screening
* Subject unwilling to limit alcohol consumption for the duration of the study: male subjects to a maximum of 3 drinks (30 g) per day, and \<12 drinks (120 g) per week; female subjects to a maximum of 2 drinks (20 g) per day, and \<8 drinks (80 g) per week
* Known allergy or hypersensitivity to simvastatin
* Undergoing or has undergone treatment with another investigational drug, biologic agent, or device within 3 months, or 3 half lives, prior to screening, whichever is longer

Primary outcomes:
measure: Percent reduction in LDL-cholesterol from baseline
timeFrame: From baseline measurement
Secondary outcomes:
measure: Percent reduction in apoB-100
timeFrame: From baseline measurement
measure: Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration
timeFrame: From baseline measurement
measure: Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
timeFrame: From baseline measurement
measure: AEs, SAEs, physical examination data, vital signs, and laboratory analyzes
timeFrame: Duration of study
Other outcomes:
Locations:
city: Auburn
country: United States
state: Maine
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Akdim F, Stroes ES, Sijbrands EJ, Tribble DL, Trip MD, Jukema JW, Flaim JD, Su J, Yu R, Baker BF, Wedel MK, Kastelein JJ. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010 Apr 13;55(15):1611-8. doi: 10.1016/j.jacc.2009.11.069.