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

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Bococizumab (PF-04950615; RN316)

About this trial

This is an interventional basic science trial for Hypercholesterolemia focused on measuring pharmacokinetics, bioavailability, PF-04950615

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Anaheim Clinical Trials, LLC
Miami Research Associates
MRA Clinical Research, LLC
Vince & Associates Clinical Research, Inc.
Vince & Associates Clinical Research, Inc.
Clinical Trials of Texas, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Single 150 mg PF-04950615 dose administered to the abdomen

Single 150 mg PF-04950615 dose administered to the upper arm

Single 150 mg PF-04950615 dose administered to the thigh

Arm Description

Outcomes

Primary Outcome Measures

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.

Maximum Observed Plasma Concentration (Cmax)

Maximum observed concentration.

Secondary Outcome Measures

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.

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time for maximum observed concentration.

Apparent Clearance (CL/F)

Apparent clearance following subcutaneous administration.

Apparent Volume of Distribution (Vz/F)

Apparent volume of distribution following subcutaneous administration.

Terminal Elimination Half-Life (t1/2)

Terminal elimination half-life following subcutaneous administration.

Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value

Maximum LDL-C response using absolute on trial LDL-C data

Emax: Change From Baseline

LDL-C Emax expressed as change from baseline.

Emax: Percent Change From Baseline

LDL-C Emax expressed as percent change from baseline.

Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C)

Time to LDL-C Emax

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

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

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.

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).

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.

Anti-Drug Antibody (ADA) Titer

ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint.

Neutralizing Antibody (nAb) Titer

nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint.

Full Information

NCT ID

NCT02043301

First Posted

January 21, 2014

Last Updated

February 14, 2019

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT02043301

Brief Title

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

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

April 2014 (Actual)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

Keywords

pharmacokinetics, bioavailability, PF-04950615

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single 150 mg PF-04950615 dose administered to the abdomen

Arm Type

Active Comparator

Arm Title

Single 150 mg PF-04950615 dose administered to the upper arm

Arm Type

Experimental

Arm Title

Single 150 mg PF-04950615 dose administered to the thigh

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Bococizumab (PF-04950615; RN316)

Intervention Description

Single 150 mg PF-04950615 dose administered SC to the abdomen

Intervention Type

Biological

Intervention Name(s)

Bococizumab (PF-04950615; RN316)

Intervention Description

Single 150 mg PF-04950615 dose administered SC to the upper arm

Intervention Type

Biological

Intervention Name(s)

Bococizumab (PF-04950615; RN316)

Intervention Description

Single 150 mg PF-04950615 dose administered SC to the thigh

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)

Description

AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.

Time Frame

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.

Title

Maximum Observed Plasma Concentration (Cmax)

Description

Maximum observed concentration.

Time Frame

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 Measure Information:

Title

Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)

Description

AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.

Time Frame

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.

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Description

Time for maximum observed concentration.

Time Frame

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.

Title

Apparent Clearance (CL/F)

Description

Apparent clearance following subcutaneous administration.

Time Frame

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.

Title

Apparent Volume of Distribution (Vz/F)

Description

Apparent volume of distribution following subcutaneous administration.

Time Frame

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.

Title

Terminal Elimination Half-Life (t1/2)

Description

Terminal elimination half-life following subcutaneous administration.

Time Frame

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.

Title

Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value

Description

Maximum LDL-C response using absolute on trial LDL-C data

Time Frame