Safety, efficacy, and pharmacokinetics of icatibant treatment in Japanese pediatric patients with hereditary angioedema: A phase 3, open-label study.

We evaluated the safety, efficacy, and pharmacokinetics of subcutaneous weight-adjusted icatibant for the treatment of acute hereditary angioedema attacks in Japanese pediatric patients. Two patients (aged 10-13 and 6-9 years) received icatibant for a total of four attacks. Each attack was abdominal and/or cutaneous and was treated with a single icatibant injection. Mild or moderate injection-site reactions were the only adverse events reported. Time to onset of symptom relief was 0.9-1.0 h. Icatibant was rapidly absorbed, with a pharmacokinetic profile consistent with previous studies. Simulated exposure levels were consistent with non-Japanese pediatric patients. These results support the safety and efficacy of icatibant in Japanese pediatric patients.

Pharmacokinetics, safety, and tolerability of sodium phenylacetate and sodium benzoate in healthy Japanese volunteers: A phase I, single-center, open-label study.

TAK-123, a combination of sodium phenylacetate (NaPA) and sodium benzoate (NaBZ), is an intravenously administered drug developed for the treatment of acute hyperammonemia in infants, children, and adults with urea cycle enzyme deficiencies. The aim of the current study was to evaluate the pharmacokinetics, safety, and tolerability after intravenous infusion of TAK-123 in Japanese healthy adult volunteers. Ten volunteers received a 3.75 g/m2 loading dose of TAK-123 over a period of 1.5 h followed by a maintenance infusion of the same dose over 24 h. Phenylacetate (PA) and benzoate (BZ) and their respective metabolites, phenylacetylglutamine (PAG) and hippurate (HIP) were measured over a 24-h period using a high-performance liquid chromatography/tandem mass spectrometry method. Non-compartmental analysis was performed using WinNonlin® Professional. During the loading dose, plasma levels of both PA and BZ peaked at 1.5 h. Plasma PA levels plateaued and were maintained up to 6.5 h, whereas plasma BZ levels declined rapidly after switching to maintenance infusion. Urinary excretion ratios of PAG and HIP at 48 h after the administration were 99.3% and 104%, respectively, suggesting that almost all NaPA and NaBZ were metabolized and excreted into urine. Overall, TAK-123 was well-tolerated in healthy Japanese adults.

Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers.

TAK-875 is a selective G-protein-coupled receptor 40 agonist in development for the treatment of type 2 diabetes mellitus. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-875 following administration of a single oral dose of TAK-875 (25-800 mg) in 60 healthy volunteers. TAK-875 was eliminated slowly with a mean terminal elimination t(1/2) of approximately 28.1 to 36.6 hours. Systemic exposure of TAK-875 did not exhibit dose-proportional increases across the dose range evaluated due to a greater than proportional increase in exposure at doses greater than 200 mg. A preliminary food effect assessment indicated that coadministration of TAK-875 with a high-fat meal decreased C(max) of TAK-875 by 40% and AUC by 17%. Clinical adverse experiences were generally mild and transient. No dose-dependent pattern was observed. In healthy volunteers, no glucose-lowering effect and no increase in insulin or c-peptide secretion were evident following administration of TAK-875; the frequency of plasma glucose concentrations <70 mg/dL was similar in the TAK-875 and pooled placebo groups. TAK-875 was well tolerated in the study and has pharmacokinetic characteristics suitable for a once-daily regimen. The pharmacodynamic data support the notion that TAK-875, if effective in diabetic patients, may bear a low risk of hypoglycemia.