Elevated LDL-Cholesterol (LDL-C)
Conditions
Brief summary
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of ALN-PCS02 in subjects with Elevated LDL-Cholesterol (LDL-C).
Interventions
DRUGALN-PCS02
Dose levels between 15 and 400 μg/kg by intravenous (IV) infusion
DRUGSterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Elevated LDL-C of \>3.0 mmol/L and \<5.7 mmol/L * Fasting triglyceride concentration ≤2.8 mmol/L * Body weight \>60.0 kg; body mass index (BMI) between 19.00 kg/m2 and \<35.00 kg/m2 * Adequate blood counts, liver and renal function * May not received any lipid lowering drug/agent within the 30 days prior to the screening * Non-smokers for at least 3 months * Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use an adequate method of birth control * Males agree to use appropriate contraception * Willing and able to comply with protocol-required visit schedule and visit requirements and provide written informed consent
Exclusion criteria
* Known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection * Multiple drug allergies or know sensitivity to oligonucleotide * History of drug abuse and/or alcohol abuse * Receiving an investigational agent within 3 months prior to study drug administration * Subjects with safety laboratory test results deemed clinical significant by the Investigator; * Received prescription drugs within 4 weeks of first dosing * Subjects who have donated more than 500 mL of blood within the 3 months prior to ALN-PCS02 or placebo administration; * Received megadose vitamin therapy or dietary supplements within 4 weeks prior to screening * Subjects who have used prescription drugs within 4 weeks of first dosing * Considered unfit for the study by the Principal Investigator * Employee or family member of the sponsor or the clinical study site personnel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation. | Up to 28 days |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) of ALN-PCS02 (Cmax, tmax, t1/2, AUC0-last, CL). | Up to 180 days |
| Effect of ALN-PCS02 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to pretreatment/Baseline PCSK9 Level). | Up to 28 days |
| Effect of ALN-PCS02 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to pretreatment/Baseline LDL-c Level). | Up to 28 days |
Countries
United Kingdom
Outcome results
None listed