Clinical trial NCT00216463: Safety and Tolerability of Varying Load and Dose of ISIS 301012 in People With Elevated LDL-cholesterol Levels
Official title: A Phase 2, Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Varying Loading and Maintenance Dosing Regimens of ISIS 301012 Administered to Hypercholesterolemic Subjects
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: 2005-09-22
Enrollment: 50
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 and tolerability of varying dose and load regimens of ISIS 301012 in people who have elevated LDL-cholesterol levels.


Eligibility criteria: Inclusion Criteria:

* BMI \>/= 25 to \</= 32 kg/m\^2
* fasting stable LDL-cholesterol \>/= 130 mg/dL (3.36 mmol/L) and triglycerides \< 400 mg/dL (4.55 mmol/L)
* Females not of childbearing potential

Exclusion Criteria:

* No endocrine, hematologic, renal, hepatic, metabolic, psychiatric, neurology, pulmonary or cardiovascular disease
* Subjects who test positive for hepatitis B, C or HIV
* Current diagnosis or known history of liver disease, such as acute or chronic hepatitis, liver cirrhosis, liver steatosis, or liver function abnormalities such as AST, ALT, GGT, or total bilirubin \>/= 1.5 x ULN at Screening
* A systolic blood pressure \>/= 160 mmHg or a diastolic blood pressure \>/= 95 mmHg on 2 occasions during Screening
* Concomitant medications within 14 days of dosing, except hormone replacement therapy for post-menopausal women and acetylsalicylic acid or paracetamol dosed for fewer than five consecutive days
* Subject has taken any lipid-lowering drug within 30 days or five half-lives (of the lipid-lowering drug) whichever is longer, prior to Screening
* Alcohol or drug abuse within 2 years of Screening
* Donated blood (450 mL) within the 3 months prior to Screening or suffered significant blood loss equal to a blood donor portion
* Subject smokes \> 10 cigarettes, or more than one pipe or one cigar per day

Primary outcomes:
measure: Percent reduction in LDL-cholesterol from baseline
timeFrame: 14 days post dosing
Secondary outcomes:
measure: Percent reduction in apoB-100 from baseline
timeFrame: 14 days post dosing
measure: Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL and LP(a)
timeFrame: 14 days post dosing
measure: Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
timeFrame: 14 days post dosing
Other outcomes:
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Akdim F, Tribble DL, Flaim JD, Yu R, Su J, Geary RS, Baker BF, Fuhr R, Wedel MK, Kastelein JJ. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J. 2011 Nov;32(21):2650-9. doi: 10.1093/eurheartj/ehr148. Epub 2011 May 18.