This Phase 1 study has been designed to evaluate the absolute bioavailability of PF-04950615 (RN316) in subjects with hypercholesterolemia who are not currently on lipid-lowering therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
49
Dose A - single-dose intravenous infusion
Dose B - single-dose subcutaneous injection
Dose C - single-dose subcutaneous injection
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States
Elite Research Institute
Miami, Florida, United States
Vince and Associates Clinical Research
Overland Park, Kansas, United States
PAREXEL International - Baltimore Early Phase Clinical Unit
Baltimore, Maryland, United States
Maximum Observed Plasma Concentration (Cmax) of PF-04950615
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-04950615
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance (CL/F) is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Clearance (CL) of PF-04950615 Intravenous Group
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups
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Dose D - single-dose subcutaneous injection
Jasper Clinic, Inc.
Kalamazoo, Michigan, United States
Prism Research
Saint Paul, Minnesota, United States
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, United States
Volume of distribution (Vz) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is determined when overall intake of drug is in dynamic equilibrium with its elimination.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Terminal Elimination Half-life (t1/2) of PF-04950615
t1/2 is the time measured for the plasma concentration of drug to decrease by one half.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Absolute Bioavailability of PF-04950615 Subcutaneous Groups
Bioavailability is defined as the rate and extent to which the active moiety administered drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was estimated by comparing log-transformed dose-normalized AUClast for subcutaneous to intravenous dose.
Time frame: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85
Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 85
Baseline was the average of observations collected on Days 7 and 1 prior to the study treatment administration.
Time frame: Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85
Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL
Time frame: Day 1 up to Day 85