Safety and pharmacokinetics of Alpha-1 MP (Prolastin®-C) in Japanese patients with alpha1-antitrypsin (AAT) deficiency.

Abstract

BACKGROUND\nAlpha1-Proteinase Inhibitor, Modified Process (Alpha-1 MP) is used for augmentation therapy in alpha1-antitrypsin deficiency (AATD), an extremely rare disease in Japan. Weekly doses of 60\u202fmg/kg Alpha-1 MP have been shown to be safe and well tolerated in non-Japanese subjects, but the safety and pharmacokinetics (PK) have not been evaluated in Japanese subjects. The objectives of this study were to evaluate the safety and PK of 60\u202fmg/kg Alpha-1 MP administered by weekly IV infusions over 8 weeks in Japanese subjects with AATD.\n\n\nMETHODS\nThis was a multicenter, open-label trial in Japanese adults aged ≥20 years with AATD. Samples for evaluation of serum alpha1-PI concentration and PK parameters were collected at 10 time points until the seventh day after the last dose at Week 8: immediately before dosing, immediately after dosing (time 0), and 0.25, 2, 4, 8, 24, 48, 120, and 168\u202fhours after dosing.\n\n\nRESULTS\nFour subjects were analyzed. The median tmax was 0.534\u202fh. Mean\u200a± SD values for t½, Cmax, and AUC0-7days were 150.4\u200a± 36.18\u202fh, 174.2\u200a± 30.51\u202fmg/dL, and 14,913.2\u200a± 1633.45\u202fmg*h/dL, respectively. Mean trough concentration at week 8 was 55.4\u200a± 7.23\u202fmg/dL. Alpha-1 MP therapy was safe, with no serious adverse events or deaths reported. Two treatment-emergent adverse events of fatigue in one subject were considered to be possibly related.\n\n\nCONCLUSIONS\nThe PK and safety of Alpha-1 MP in Japanese subjects with AATD were consistent with the Alpha-1 MP profile in non-Japanese subjects (ClinicalTrials.gov: NCT02870309; JAPIC CTI: JapicCTI-163160).