Pharmacokinetics And Relative Bioavailability Of Bococizumab (PF-04950615; RN316) When Administered To The Abdomen, Thigh Or Upper Arm

A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, PARALLEL GROUP STUDY TO ASSESS INJECTION SITE RELATIVE BIOAVAILABILITY OF PF-04950615 FOLLOWING SUBCUTANEOUS ADMINISTRATION IN ADULT SUBJECTS WITH HYPERCHOLESTEROLEMIA

This study aims to characterize the single dose pharmacokinetics of PF-04950616 following subcutaneous injection to the abdomen, upper arm or the thigh.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Biological: Bococizumab (PF-04950615; RN316); Biological: Bococizumab (PF-04950615; RN316); Biological: Bococizumab (PF-04950615; RN316)

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince & Associates Clinical Research, Inc.
    • Overland Park, Kansas, United States, 66211
      • Vince & Associates Clinical Research, Inc.
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects 18 to 65 years of age.
• Body Mass Index (BMI) ≤ 33 kg/m2, and total body weight of 60 kg to 90 kg (132 lbs to 198 lbs).
• Fasting LDL-C must be > 130 mg/dL (borderline high per NCEP ATP III criteria) at two qualifying visits: initial screening (Days -28 to -14) and Day -7.

Exclusion Criteria:

• Poorly controlled type 1 or type 2 diabetes mellitus (HbA1c > 9.0%).
• History of a cardiovascular or cerebrovascular event (eg, MI, stroke, TIA) or related procedure (eg, angioplasty) during the past year.
• Subjects who meet the New York Heart Association (NYHA) criteria for congestive heart failure (CHF) classes III or IV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single 150 mg PF-04950615 dose administered to the abdomen	Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the abdomen; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the upper arm; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the thigh
Experimental: Single 150 mg PF-04950615 dose administered to the upper arm	Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the abdomen; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the upper arm; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the thigh
Experimental: Single 150 mg PF-04950615 dose administered to the thigh	Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the abdomen; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the upper arm; Biological: Bococizumab (PF-04950615; RN316); Single 150 mg PF-04950615 dose administered SC to the thigh

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)	AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Maximum Observed Plasma Concentration (Cmax)	Maximum observed concentration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)	AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Time for maximum observed concentration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Apparent Clearance (CL/F)	Apparent clearance following subcutaneous administration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Apparent Volume of Distribution (Vz/F)	Apparent volume of distribution following subcutaneous administration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Terminal Elimination Half-Life (t1/2)	Terminal elimination half-life following subcutaneous administration.	Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value	Maximum LDL-C response using absolute on trial LDL-C data	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Emax: Change From Baseline	LDL-C Emax expressed as change from baseline.	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Emax: Percent Change From Baseline	LDL-C Emax expressed as percent change from baseline.	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C)	Time to LDL-C Emax	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Area Under the LDL-C Effect Curve (AUEC): Absolute Value	AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
AUEC: Change From Baseline	AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed as change from baseline	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
AUEC: Percent Change From Baseline	AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline.	Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Number of Participants With Injection Site Reactions (ISRs) by Severity	Acute injection site reactions (e.g, pain, pruritus, induration) were captured as adverse events (AEs). Intensity of the AE was described as mild (does not interfere with usual function), moderate (interferes to some extent with usual function), or severe (interferes significantly with participant's usual function).	Day 1 to Day 85
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)	A participant is ADA positive if ADA titer (log2) >=6.23. A participant is nAb positive if nAb titer (log2) >=4.32.	Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Anti-Drug Antibody (ADA) Titer	ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint.	Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Neutralizing Antibody (nAb) Titer	nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint.	Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wang EQ, Plotka A, Salageanu J, Sattler C, Yunis C. Pharmacokinetics and pharmacodynamics of bococizumab, a monoclonal antibody to PCSK9, after single subcutaneous injection at three sites [NCT 02043301]. Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12278.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: January 21, 2014
• First Submitted That Met QC Criteria: January 21, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Actual): May 31, 2019
• Last Update Submitted That Met QC Criteria: February 14, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioavailability; PF-04950615
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bococizumab
• Other Study ID Numbers: B1481024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.