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

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

Official Title
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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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Biological: Bococizumab (PF-04950615; RN316)
* Biological: Bococizumab (PF-04950615; RN316)
* Biological: Bococizumab (PF-04950615; RN316)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, bioavailability, PF-04950615