Julie Krop1, William G Kramer2. 1. AMAG Pharmaceuticals Inc, Waltham, Massachusetts. Electronic address: jkrop@amagpharma.com. 2. Kramer Consulting LLC, North Potomac, Maryland.
Abstract
PURPOSE: The purpose of this study was to evaluate the bioavailability of hydroxyprogesterone caproate (HPC) administered as a subcutaneous injection in the back of the upper arm using a prefilled autoinjector syringe with a 27-gauge needle compared with standard intramuscular injection in the gluteus maximus using a 21-gauge needle. METHODS:Healthy postmenopausal women 50 to 75 years old were randomized in a parallel group design to receive a single SC injection of 1.1 mL (275-mg total dose) of preservative-free HPC administered using an autoinjector in the back of the upper arm or a single IM injection of 1 mL (250-mg total dose) of preservative-free HPC administered in the gluteus maximus. Blood samples were collected through 1008 hours (42 days) after injection. The primary measures were the Cmax, AUC0-t, and AUC0-∞. Secondary measures were Tmax, ke, t½, and injection site reactions captured as a treatment-emergent adverse event. FINDINGS: The pharmacokinetic population consisted of 90 individuals; 45 received subcutaneous administration and 45 received intramuscular administration. Geometric mean whole blood concentrations of HPC were comparable between administration regimens. Subcutaneous administration resulted in a higher geometric mean Cmax than intramuscular administration (7.88 vs 6.91 ng/mL), but median Tmax values were comparable (48.1 vs 49.7 hours). The least square geometric mean ratios for AUC0-168), AUC0-t, and AUC0-∞ were 102.89%, 110.25%, and 113.51%, respectively, with all 90% CIs within the 80.0% to 125.0% window that defined bioequivalence. The ratio for Cmax was 113.95% with a 90% CI of 91.94% to 141.23% but with substantial overlap of individual values between administration regimens. The geometric mean t½ of HPC was 212 hours for the subcutaneous administration and 188 hours for the intramuscular administration. The most common treatment-emergent adverse event was injection site pain (subcutaneous, 37.3%; intramuscular, 8.2%), described as mild (85%) to moderate (15%). IMPLICATIONS: Administration of HPC by SC injection of 1.1 mL (275 mg) via autoinjector is bioequivalent to IM injection of 1.0 mL (250 mg). ClinicalTrials.gov identifier: NCT02940522.
RCT Entities:
PURPOSE: The purpose of this study was to evaluate the bioavailability of hydroxyprogesterone caproate (HPC) administered as a subcutaneous injection in the back of the upper arm using a prefilled autoinjector syringe with a 27-gauge needle compared with standard intramuscular injection in the gluteus maximus using a 21-gauge needle. METHODS: Healthy postmenopausal women 50 to 75 years old were randomized in a parallel group design to receive a single SC injection of 1.1 mL (275-mg total dose) of preservative-free HPC administered using an autoinjector in the back of the upper arm or a single IM injection of 1 mL (250-mg total dose) of preservative-free HPC administered in the gluteus maximus. Blood samples were collected through 1008 hours (42 days) after injection. The primary measures were the Cmax, AUC0-t, and AUC0-∞. Secondary measures were Tmax, ke, t½, and injection site reactions captured as a treatment-emergent adverse event. FINDINGS: The pharmacokinetic population consisted of 90 individuals; 45 received subcutaneous administration and 45 received intramuscular administration. Geometric mean whole blood concentrations of HPC were comparable between administration regimens. Subcutaneous administration resulted in a higher geometric mean Cmax than intramuscular administration (7.88 vs 6.91 ng/mL), but median Tmax values were comparable (48.1 vs 49.7 hours). The least square geometric mean ratios for AUC0-168), AUC0-t, and AUC0-∞ were 102.89%, 110.25%, and 113.51%, respectively, with all 90% CIs within the 80.0% to 125.0% window that defined bioequivalence. The ratio for Cmax was 113.95% with a 90% CI of 91.94% to 141.23% but with substantial overlap of individual values between administration regimens. The geometric mean t½ of HPC was 212 hours for the subcutaneous administration and 188 hours for the intramuscular administration. The most common treatment-emergent adverse event was injection site pain (subcutaneous, 37.3%; intramuscular, 8.2%), described as mild (85%) to moderate (15%). IMPLICATIONS: Administration of HPC by SC injection of 1.1 mL (275 mg) via autoinjector is bioequivalent to IM injection of 1.0 mL (250 mg). ClinicalTrials.gov identifier: NCT02940522.
Authors: Leo Turner; Lam P Ly; Reena Desai; Gurmeet K S Singh; Timothy D Handelsman; Sasha Savkovic; Carolyn Fennell; Veena Jayadev; Ann Conway; David J Handelsman Journal: J Endocr Soc Date: 2019-06-28