A Pharmacokinetic and Pharmacodynamic Study of PF-04950615 (RN316) in Subjects With Hypercholesterolemia
- Conditions
- HypercholesterolemiaHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic Diseases
- Interventions
- Biological: PF-04950615 (RN316)
- Registration Number
- NCT01435382
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- Fasting LDL-C greater than or equal to 130 mg/dL at two qualifying screening visits.
- Total body weight greater than or equal to 50 kg (110 lbs) and less than or equal to 150 kg (330 lbs)
- Lipid-lowering prescription medications, homeopaths, herbal medicines, or nutritional supplements.
- Poorly controlled type 1 or type 2 diabetes.
- History of a cardiovascular or cerebrovascular event or related procedure during the past year.
- Poorly controlled hypertension.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group D PF-04950615 (RN316) - Group B PF-04950615 (RN316) - Group C PF-04950615 (RN316) - Group A PF-04950615 (RN316) -
- Primary Outcome Measures
Name Time Method Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615 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 Maximum Observed Plasma Concentration (Cmax) of PF-04950615 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 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 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 (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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615 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 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 t1/2 is the time measured for the plasma concentration of drug to decrease by one half.
Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups 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 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.
Clearance (CL) of PF-04950615 Intravenous Group 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 of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group 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 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.
Absolute Bioavailability of PF-04950615 Subcutaneous Groups 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 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.
- Secondary Outcome Measures
Name Time Method Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C) 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 Day 1 up to Day 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, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85 Baseline was the average of observations collected on Days 7 and 1 prior to the study treatment administration.
Trial Locations
- Locations (7)
Jasper Clinic, Inc.
🇺🇸Kalamazoo, Michigan, United States
Prism Research
🇺🇸Saint Paul, Minnesota, United States
Profil Institute for Clinical Research, Inc.
🇺🇸Chula Vista, California, United States
Vince and Associates Clinical Research
🇺🇸Overland Park, Kansas, United States
PAREXEL International - Baltimore Early Phase Clinical Unit
🇺🇸Baltimore, Maryland, United States
Elite Research Institute
🇺🇸Miami, Florida, United States
Medpace Clinical Pharmacology Unit
🇺🇸Cincinnati, Ohio, United States