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

Background: Alpha(1)-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 mg/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 mg/kg Alpha-1 MP administered by weekly IV infusions over 8 weeks in Japanese subjects with AATD. Methods: This was a multicenter, open-label trial in Japanese adults aged >= 20 years with AATD. Samples for evaluation of serum alpha i -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 hours after dosing. Results: Four subjects were analyzed. The median t(max) was 0.534 h. Mean +/- SD values for t(1/2), C-max, and AUC(0-7days) were 150.4 +/- 36.18 h, 174.2 +/- 30.51 mg/dL, and 14,913.2 +/- 1633.45 mg*h/dL, respectively. Mean trough concentration at week 8 was 55.4 +/- 7.23 mg/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. Conclusions: The PK and safety of Alpha-1 MP in Japanese subjects with AATD were consistent with the Alpha-1 MP profile in non-Japanese subjects (C) 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.