Clinical trial NCT01435382: A Pharmacokinetic and Pharmacodynamic Study of PF-04950615 (RN316) in Subjects With Hypercholesterolemia
Official title: A Phase 1, Open-label, Randomized, Single Dose, Parallel Group Study To Assess The Pharmacokinetics And Pharmacodynamics Of Pf-04950615 Following Subcutaneous And Intravenous Doses In Adult Subjects With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Keywords: PF-04950615
RN316
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-09-16
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-04950615
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-04950615
timeFrame: 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
measure: Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups
timeFrame: 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
measure: Clearance (CL) of PF-04950615 Intravenous Group
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group
timeFrame: 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
measure: Terminal Elimination Half-life (t1/2) of PF-04950615
timeFrame: 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
measure: Absolute Bioavailability of PF-04950615 Subcutaneous Groups
timeFrame: 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
Secondary outcomes:
measure: Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85
measure: 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
timeFrame: Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85
measure: Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL
timeFrame: Day 1 up to Day 85
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 85
measure: Number of Adverse Events (AEs) by Severity
timeFrame: Day 1 up to Day 85
measure: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 85
measure: Number of Participants With Injection Site Reactions
timeFrame: Day 1 up to Day 3
measure: Number of Injection Site Reactions Reported as Adverse Events
timeFrame: Day 1 up to Day 3
measure: Visual Analogue Scale (VAS)
timeFrame: Day 1: Immediately post-dose, 0.5, 1.0, 2.0, 8.0 hours post-dose; Day 2, 3
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Day 1 up to Day 85
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Day 1 up to Day 85
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
timeFrame: Day 1 up to Day 85
measure: Percentage of Participants With Positive Anti-drug (Anti-PF 04950615) Antibodies
timeFrame: Day 1 up to Day 85
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Baltimore
country: United States
facility: PAREXEL International - Baltimore Early Phase Clinical Unit
state: Maryland
city: Kalamazoo
country: United States
facility: Jasper Clinic, Inc.
state: Michigan
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Udata C, Garzone PD, Gumbiner B, Joh T, Liang H, Liao KH, Williams JH, Meng X. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development. J Clin Pharmacol. 2017 Jul;57(7):855-864. doi: 10.1002/jcph.867. Epub 2017 Feb 9.