Dose-escalating Safety Study in Subjects on Stable Statin Therapy

• Register: ClinicalTrials.gov
• Last refreshed on: 15 August 2016
• Main ID: NCT00231569
• Date of registration: 03/10/2005
• Prospective Registration: No
• Primary sponsor: Kastle Therapeutics, LLC
• Public title: Dose-escalating Safety Study in Subjects on Stable Statin Therapy
• Scientific 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
• Date of first enrolment: September 2005
• Target sample size: 74
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00231569
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Netherlands, United States

Contacts

• Name: Medical Monitor
• Affiliation: Genzyme, a Sanofi Company

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: ISIS 301012 or Placebo

Primary Outcome(s)

Percent reduction in LDL-cholesterol from baseline [Time Frame: From baseline measurement]

Secondary Outcome(s)

Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration [Time Frame: From baseline measurement]

Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios [Time Frame: From baseline measurement]

AEs, SAEs, physical examination data, vital signs, and laboratory analyzes [Time Frame: Duration of study]

Percent reduction in apoB-100 [Time Frame: From baseline measurement]

Secondary ID(s)

EudraCT No.: 2005-002119-26

301012CS4

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ionis Pharmaceuticals, Inc.