Ellen Q Wang1, Anna Plotka2, Joanne Salageanu3, Catherine Sattler4, Carla Yunis5. 1. Clinical Pharmacology, Global Product Development, Pfizer Inc, New York, NY, USA. 2. Global Biometrics and Data Management, Global Product Development, Pfizer Inc, Collegeville, PA, USA. 3. Clinical Pharmacology, Global Product Development, Pfizer Inc, Groton, CT, USA. 4. Clinical Sciences and Operations, Global Product Development, Pfizer Inc, Groton, CT, USA. 5. Global Product Development CVMET Therapeutics, Pfizer Inc, New York, NY, USA.
Abstract
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS:Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm. Blood samples for bococizumab and lipids were collected for 12 weeks postdose. RESULTS:Plasma bococizumab concentration-time profiles and PK parameters were generally similar across injection sites. Mean maximum observed concentration (Cmax ) ranged from 8.14 to 11.9 μg/mL, and area under the concentration-time curve (AUCinf ) ranged from 160.3 to 198.9 µg∙day/mL. The median time to Cmax (Tmax ) ranged from 4.25 to 6.93 days. Similar LDL-C concentration-time profiles were observed across injection sites, with mean (% coefficient of variation) maximum reductions in LDL-C of -57.5% (15.8), -57.0% (25.9), and -55.0% (24.1) for the abdomen, thigh, and upper arm, respectively. Adverse events (AEs) were mostly mild and generally similar across injection sites. Commonly reported AEs were upper respiratory tract infection (9.3%), headache (6.7%), and injection site reaction (6.7%). One serious AE was reported (ischemic colitis), which was not considered related to study drug. CONCLUSIONS:Similar PK profiles and robust LDL-C reductions were observed following a single 150-mg s.c. injection of bococizumab administered to the abdomen, thigh, or upper arm in untreated subjects with LDL-C ≥130 mg/dL. Bococizumab was generally well tolerated following a single 150-mg s.c. administration in this subject population.
RCT Entities:
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm. Blood samples for bococizumab and lipids were collected for 12 weeks postdose. RESULTS: Plasma bococizumab concentration-time profiles and PK parameters were generally similar across injection sites. Mean maximum observed concentration (Cmax ) ranged from 8.14 to 11.9 μg/mL, and area under the concentration-time curve (AUCinf ) ranged from 160.3 to 198.9 µg∙day/mL. The median time to Cmax (Tmax ) ranged from 4.25 to 6.93 days. Similar LDL-C concentration-time profiles were observed across injection sites, with mean (% coefficient of variation) maximum reductions in LDL-C of -57.5% (15.8), -57.0% (25.9), and -55.0% (24.1) for the abdomen, thigh, and upper arm, respectively. Adverse events (AEs) were mostly mild and generally similar across injection sites. Commonly reported AEs were upper respiratory tract infection (9.3%), headache (6.7%), and injection site reaction (6.7%). One serious AE was reported (ischemic colitis), which was not considered related to study drug. CONCLUSIONS: Similar PK profiles and robust LDL-C reductions were observed following a single 150-mg s.c. injection of bococizumab administered to the abdomen, thigh, or upper arm in untreated subjects with LDL-C ≥130 mg/dL. Bococizumab was generally well tolerated following a single 150-mg s.c. administration in this subject population.
Authors: Ellen Q Wang; Jack F Bukowski; Carla Yunis; Charles L Shear; Paul M Ridker; Pamela F Schwartz; Daniel Baltrukonis Journal: BioDrugs Date: 2019-10 Impact factor: 5.807