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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00216463
• Other study ID #: 301012CS3
• Secondary ID: EudraCT No.: 200
• Status: Completed
• Phase: Phase 2
• First received: September 19, 2005
• Last updated: August 1, 2016
• Start date: August 2005
• Est. completion date: August 2007

Study information

• Verified date: August 2016
• Source: Kastle Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

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
200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 200 mg subcutaneous injection - every other week for 11 weeks
• ISIS 301012 or Placebo
200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 100 mg subcutaneous injection - every other week for 11 weeks
• ISIS 301012 or Placebo
300 mg subcutaneous injection - every week for 13 weeks
• ISIS 301012 or Placebo
400 mg subcutaneous injection - every week for 13 weeks
• ISIS 301012 or Placebo
200 mg subcutaneous injection - every week for 13 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

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

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent reduction in LDL-cholesterol from baseline		14 days post dosing	No
Secondary	Percent reduction in apoB-100 from baseline		14 days post dosing	No
Secondary	Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL and LP(a)		14 days post dosing	No
Secondary	Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios		14 days post dosing	No