Purpose: Severe congenital protein C deficiency (SCPCD) is a rare, life-threatening disorder. Plasma-derived protein C concentrate is recommended for the acute and long-term management of SCPCD; however, data in Japanese patients are lacking. In this study, the pharmacokinetics (PK) and safety of protein C concentrate were investigated in a Japanese population. Patients and Methods: This study was an open-label, phase 1/2, nonrandomized, noncontrolled, multicenter clinical trial in Japanese patients with SCPCD (ClinicalTrials.gov: NCT04984889). Patients received a single intravenous dose (80 IU/kg) of human plasma-derived protein C concentrate. The primary endpoints were plasma protein C activity levels and PK parameters. Secondary endpoints for safety included adverse events (AEs). Results: All five enrolled patients (mean age, 15.2 years; mean weight, 34.0 kg) received the predefined dose of protein C concentrate and were included in PK and safety analyses. The geometric mean (coefficient of variation CV%) maximum concentration (C max ) was 1.679 IU/mL (31.7%) and the geometric mean (CV%) area under the curve (AUC inf ) was 21.88 IU·h/mL (47.1%). The median (range) half-life for protein C in plasma was 10.7 (7.35– 12.4) hours. C max and AUC inf tended to be higher in older patients (≥ 20 years old) than in younger patients (< 20 years old), whereas half-life was similar regardless of age. One patient had a mild treatment-related AE of pyrexia. No serious AEs or deaths were reported. Conclusion: PK parameters for protein C concentrate in Japanese patients with SCPCD were determined to be comparable to studies in western populations. A single intravenous 80 IU/kg dose was well tolerated, with no serious treatment-related AEs. Keywords: pharmacokinetics, phase 1/2 clinical trials, protein C concentrate, protein C deficiency, SCPCD, thrombotic disorders
Koh et al. (Sun,) studied this question.