Pharmacokinetics And Relative Bioavailability Of Bococizumab (PF-04950615; RN316) When Administered To The Abdomen, Thigh Or Upper Arm
- Conditions
- Hypercholesterolemia
- Interventions
- Biological: Bococizumab (PF-04950615; RN316)
- Registration Number
- NCT02043301
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Single 150 mg PF-04950615 dose administered to the abdomen Bococizumab (PF-04950615; RN316) - Single 150 mg PF-04950615 dose administered to the upper arm Bococizumab (PF-04950615; RN316) - Single 150 mg PF-04950615 dose administered to the thigh Bococizumab (PF-04950615; RN316) -
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) 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 concentration.
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) 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. AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.
- Secondary Outcome Measures
Name Time Method Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) 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. AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) 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 LDL-C Emax
AUEC: 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 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 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 is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline.
Time to Reach Maximum Observed Plasma Concentration (Tmax) 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 for maximum observed concentration.
Apparent Clearance (CL/F) 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 following subcutaneous administration.
Emax: 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 LDL-C Emax expressed as change from baseline.
Area Under the LDL-C Effect Curve (AUEC): Absolute 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 is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value
Apparent Volume of Distribution (Vz/F) 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 following subcutaneous administration.
Terminal Elimination Half-Life (t1/2) 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 following subcutaneous administration.
Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute 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 Maximum LDL-C response using absolute on trial LDL-C data
Emax: 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 LDL-C Emax expressed as percent change from baseline.
Anti-Drug Antibody (ADA) Titer Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
Number of Participants With Injection Site Reactions (ISRs) by Severity Day 1 to Day 85 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) Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination A participant is ADA positive if ADA titer (log2) \>=6.23. A participant is nAb positive if nAb titer (log2) \>=4.32.
Neutralizing Antibody (nAb) Titer Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
Trial Locations
- Locations (5)
Vince & Associates Clinical Research, Inc.
🇺🇸Overland Park, Kansas, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
MRA Clinical Research, LLC
🇺🇸South Miami, Florida, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
Clinical Trials of Texas, Inc.
🇺🇸San Antonio, Texas, United States