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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02043301
• Other study ID #: B1481024
• Status: Completed
• Phase: Phase 1
• Start date: April 2014
• Est. completion date: November 2014

Study information

• Verified date: February 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Biological:
• Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the abdomen
• Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the upper arm
• Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the thigh

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Vince & Associates Clinical Research, Inc.	Overland Park	Kansas
United States	Vince & Associates Clinical Research, Inc.	Overland Park	Kansas
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Miami Research Associates	South Miami	Florida
United States	MRA Clinical Research, LLC	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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