Clinical trial NCT01243151: Safety And Tolerability Of Multiple Doses Of PF-04950615 (RN316) In Subjects With Hypercholesterolemia
Official title: A Phase 1, Placebo-controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Multiple Intravenous Doses Of Pf-04950615 In Healthy Adult Subjects With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Dyslipidemia
Keywords: Hypercholesterolemia
Dyslipidemia
LDL
High Cholesterol
Japanese Volunteers
PF-04950615
RN316
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-11-18
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of repeated doses of PF-04950615 (RN316) in study volunteers with hypercholesterolemia. PF-04950615 is an investigational drug that is currently being studied as a lipid lowering agent.


Eligibility criteria: Inclusion Criteria:

* LDL-C must be greater or equal to 130 mg/dl
* BMI must be between 18.5 and 40 kg/m2
* Japanese volunteers must have 4 Japanese grand parents born in Japan

Exclusion Criteria:

* History of cardiovascular or cerebrovascular event during the past year.
* Poorly controlled type 1 or type 2 diabetes mellitus
* Subjects who have taken lipid lowering therapies within the last 3 months of screening.

Primary outcomes:
measure: Number of Participants With Dose Limiting and Intolerable Treatment-Related Adverse Events (AEs)
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-Related Adverse Events (AEs)
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Adverse Events (AEs) by Severity
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Clinically Relevant Changes in Vital Signs
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to Follow-up period (Day 78)
measure: Number of Participants With Anti-drug Antibodies (ADA)
timeFrame: Baseline up to Follow-up period (Day 78)
Secondary outcomes:
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615
timeFrame: Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
timeFrame: Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax) of PF-04950615
timeFrame: Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Plasma Decay Half-Life (t1/2) of PF-04950615
timeFrame: Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Apparent Clearance (CL) of PF-04950615
timeFrame: Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Volume of Distribution at Steady State (Vss) of PF-04950615
timeFrame: Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Accumulation Ratio (Rac) of PF-04950615
timeFrame: Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
measure: Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Number of Participants Achieving LDL-C Less Than (<) 70 Milligram Per Deciliter (mg/dL)
timeFrame: Day 15, 22, 29 and 36
measure: Number of Participants Achieving LDL-C Less Than (<) 100 Milligram Per Deciliter (mg/dL)
timeFrame: Day 15, 22, 29 and 36
measure: Number of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in LDL-C From Baseline
timeFrame: Baseline, Day 15, 22, 29 and 36
measure: Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Change From Baseline in Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Change From Baseline in Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Change From Baseline in Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78
timeFrame: Baseline, Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline In Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline In Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline In Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Percent Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78
timeFrame: Day 8, 15, 22, 29 and 78
measure: Change From Baseline In Low Density Lipoprotein Cholesterol (LDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: Change From Baseline In Small Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: Change From Baseline In Medium Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: Change From Baseline In Large Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: Change From Baseline In Total Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Levels at Baseline, Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Baseline, Day 8, 15, 22, 36, 50, 64 and 78
measure: C-Reactive Protein Levels at Day 8, 15, 21, 36, 57 and 78
timeFrame: Day 8, 15, 21, 36, 57 and 78
measure: Small High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Medium High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Large High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Total High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Small Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Medium Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Large Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Total Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: High Density Lipoprotein-Cholesterol (HDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
measure: Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78
timeFrame: Day 8, 15, 22, 36, 50, 64 and 78
Other outcomes:
Locations:
city: Culver City
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Honolulu
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Hawaii
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
city: San Antonio
country: United States
facility: Healthcare Discoveries, LLC dba ICON Development Solutions
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wan H, Gumbiner B, Joh T, Riel T, Udata C, Forgues P, Garzone PD. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition with Bococizumab on Lipoprotein Particles in Hypercholesterolemic Subjects. Clin Ther. 2017 Nov;39(11):2243-2259.e5. doi: 10.1016/j.clinthera.2017.09.009. Epub 2017 Oct 14.
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.