Safety and Tolerability of Varying Load and Dose of ISIS 301012 in People With Elevated LDL-cholesterol Levels

Kastle Therapeutics

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: ISIS 301012 or Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00216463

301012CS3

EudraCT No.: 2004-003934-32

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 5 patient groups

A

Experimental group

Description:

Slow load with every other week maintenance

Treatment:

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

B

Experimental group

Description:

Slow load with every other week maintenance

Treatment:

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

C

Experimental group

Description:

No load; once weekly maintenance

Treatment:

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

D

Experimental group

Description:

No load; once weekly maintenance

Treatment:

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

E

Experimental group

Description:

No load; once weekly maintenance

Treatment:

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo

Drug: ISIS 301012 or Placebo