PURPOSE: @entity112 ( @entity69949 ) injection has been approved in Europe for the treatment of adults with @entity3052 , used in combination therapy with the T-cell-derived cytokine @entity1199 . Despite years of clinical applications of @entity69949 in Europe, no data are available on its tolerability and pharmacokinetic properties in Chinese @entity1 . The objective of this study was to determine the safety profile and pharmacokinetic properties of @entity69949 in Chinese healthy volunteers (HVs). METHODS: In this Phase I, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg @entity69949 via a 10-minute subcutaneous injection. Whole-blood and urine samples were collected at designated time points after dosing. Plasma and urine concentrations of @entity112 and metabolite @entity41020 were measured using a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated through noncompartmental procedures based on concentration-time data. Adverse events and evaluation of clinical laboratory tests were used to assess the safety profile. The pharmacokinetic profile for a single-dose of 1.0 mg @entity69949 in Chinese HVs was compared with that in Western HVs. FINDINGS: No severe adverse events occurred in this study, and the severity of all adverse events was grade I according to the Common Terminology Criteria for Adverse Events, version 4.0. For the pharmacokinetic parameters of @entity112 at the 0.5-mg and 1.0-mg dose levels, t   was 0.50 and 1.02 hours; Tmax was 0.15 and 0.14 hours; mean Cmax was 26.59 and 71.01 nmol/L; AUC0-t was 8.35 and 20.43 nmol/h/L; AUC0-    was 9.61 and 22.69 nmol/h/L; accumulated amount excreted in urine within 24 hours was 125.93 and 145.52 nmol; and maximum urine excretion rates were 21.85 and 38.94 nmol/h, respectively. For @entity41020 at the 0.5-mg and 1.0-mg dose levels, t   was 0.58 and 0.66 hours; Tmax was 0.28 and 0.26 hours; mean Cmax was 17.01 and 23.54 nmol/L; AUC0-t was 7.72 and 17.08 nmol/h/L; AUC0-    was 9.01 and 19.62 nmol/h/L; accumulated amount excreted in urine within 24 hours was 331.7 and 583.21 nmol; and maximum urine excretion rates were 53.29 and 133.53 nmol/h, respectively. IMPLICATIONS: Both single-dose 0.5 mg and 1.0 mg @entity69949 were well tolerated in Chinese HVs, and the pharmacokinetic profile of @entity69949 in Chinese HVs was characterized in this study. A single dose of 1.0 mg @entity69949 had a more rapid but similar extent of absorption, a wider distribution, and a little more rapid elimination in Chinese HVs compared with Western HVs. Findings from this study support additional clinical trials for @entity69949 using in Chinese @entity1 . Chinese Clinical Trial Registry identifier: ChiCTR-ONC-13003954.

Pharmacokinetic Properties and Safety Profile of XXXX Injection in Chinese Healthy Volunteers: A Phase I, Single-center, Open-label, Randomized Study.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia'] @entity69949 :: ('CHEBI:59112', 'Chemical') :: ['HDC'] @entity112 :: ('MESH:D006632', 'Chemical') :: ['histamine', 'Histamine dihydrochloride'] @entity1199 :: ('3558', 'Gene') :: ['interleukin-2'] @entity41020 :: ('MESH:C048140', 'Chemical') :: ['N-methyl histamine']
@entity112 :: (MESH:D006632,Chemical) :: ['Histamine Dihydrochloride']
