Clinical trial NCT02043301: Pharmacokinetics And Relative Bioavailability Of Bococizumab (PF-04950615; RN316) When Administered To The Abdomen, Thigh Or Upper Arm
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Keywords: pharmacokinetics
bioavailability
PF-04950615
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-01-23
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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 outcomes:
measure: Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
timeFrame: 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.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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.
measure: Apparent Clearance (CL/F)
timeFrame: 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.
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 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.
measure: Terminal Elimination Half-Life (t1/2)
timeFrame: 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.
measure: Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value
timeFrame: 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
measure: Emax: Change From Baseline
timeFrame: 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
measure: Emax: Percent Change From Baseline
timeFrame: 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
measure: Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C)
timeFrame: 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
measure: Area Under the LDL-C Effect Curve (AUEC): Absolute Value
timeFrame: 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
measure: AUEC: Change From Baseline
timeFrame: 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
measure: AUEC: Percent Change From Baseline
timeFrame: 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
measure: Number of Participants With Injection Site Reactions (ISRs) by Severity
timeFrame: Day 1 to Day 85
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
timeFrame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
measure: Anti-Drug Antibody (ADA) Titer
timeFrame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
measure: Neutralizing Antibody (nAb) Titer
timeFrame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research, LLC
state: Florida
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research, Inc.
state: Kansas
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research, Inc.
state: Kansas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.