Dose-escalating Safety Study in Subjects on Stable Statin Therapy

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00231569
• Other study ID #: 301012CS4
• Secondary ID: EudraCT No.: 200
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2005
• Last updated: August 1, 2016
• Start date: September 2005
• Est. completion date: December 2007

Study information

• Verified date: December 2013
• Source: Kastle Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: December 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• ISIS 301012 or Placebo
30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
• ISIS 301012 or Placebo
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
• ISIS 301012 or Placebo
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
• ISIS 301012 or Placebo
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
• ISIS 301012 or Placebo
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
• ISIS 301012 or Placebo
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
• ISIS 301012 or Placebo
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Kastle Therapeutics, LLC	Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent reduction in LDL-cholesterol from baseline		From baseline measurement	No
Secondary	Percent reduction in apoB-100		From baseline measurement	No
Secondary	Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration		From baseline measurement	No
Secondary	Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios		From baseline measurement	No
Secondary	AEs, SAEs, physical examination data, vital signs, and laboratory analyzes		Duration of study	Yes