Abstract Antiviral therapy is needed to address acute coronavirus disease. EGT710 is a novel low‐molecular‐weight inhibitor of the coronavirus main protease (M pro ). This first‐in‐human study evaluated the safety, tolerability, and pharmacokinetics of EGT710 in healthy adults. The study conducted in the Netherlands involved three parts: a blinded, placebo‐controlled, 3:1 randomized, single ascending dose Part A (n = 39); a multiple ascending dose Part B (n = 31); and an open‐label, three‐period, six sequence, randomized, cross‐over Part C (n = 18) to evaluate food and formulation effects on EGT710 bioavailability. EGT710 was well tolerated. All adverse events (AEs) were mild (Grade 1), with no serious AEs or discontinuations. Aside from mild gastrointestinal AEs associated with EGT710, AE frequency was similar between groups with no dose‐dependent or dose‐limiting adverse effects. EGT710 was rapidly absorbed (median T max 2.0 h), showed sub‐proportional AUC and C max increases and no significant accumulation with daily dosing. Bioavailability was comparable between suspension and capsule formulations. Food increased C max by 20% and AUC by 27%. EGT710 700 mg once daily for 7 days modestly induced CYP3A4 activity but had no effect on organic anion transporting polypeptide (OAT1/3) activity. Oral EGT710 (capsule and suspension) was safe and well tolerated, with pharmacokinetics that support further development as a treatment for coronavirus disease.
Abstract Enzalutamide is an oral second‐generation androgen receptor inhibitor used for advanced prostate cancer. This study evaluated the pharmacokinetics (PK), bioequivalence (BE), and safety of a newly developed generic enzalutamide soft capsule (test) compared with the reference product (XTANDI) in healthy Chinese adults under fasting and fed conditions. A single‐center, randomized, open‐label, two‐period, two‐sequence, crossover study was conducted in 72 male participants (36 fasting and 36 fed). Each participant received a single 40‐mg dose of test or reference formulation, separated by a 34‐day washout. Blood samples were collected up to 72 h post‐dose. PK parameters (C max and AUC 0‐72 h ) were calculated using non‐compartmental analysis. BE was assessed by 90% confidence intervals (CIs) of geometric mean ratios (GMRs). Safety was monitored throughout the study. In both fasting and fed conditions, the 90% CIs of GMRs for C max and AUC 0‐72 h were within the predefined 80%–125% BE range. Both formulations exhibited a favorable single‐dose safety profile, with no serious adverse events reported. The test enzalutamide soft capsule is bioequivalent to the reference product in healthy Chinese volunteers, demonstrating similar PK profiles and safety. This study provides population‐specific PK evidence supporting the clinical use of the generic formulation in China.
Abstract This Phase I, randomized, placebo‐controlled, double‐blind study (NCT06625489) evaluated pharmacokinetics (PK), safety, and tolerability of the transglutaminase 2 inhibitor suvigletistat in Chinese, Japanese, and White/European participants. Eligible participants: aged 18–50 years, healthy, and of Chinese, Japanese, or White/European ancestry. Thirty‐six participants (12 per ancestry group) were randomized 3:1 to receive suvigletistat (160 mg single oral dose) or placebo. Suvigletistat was rapidly absorbed (median time to maximum observed drug concentration [C max ]: 0.67–0.75 h), and geometric mean half‐life ranged from 1.93 to 2.58 h across ancestry groups. Suvigletistat systemic exposure was similar across all ancestries; geometric least squares mean ratios versus White/European participants for C max were 0.99 and 1.06 in participants of Chinese and Japanese ancestry, respectively. Similarly, area under the concentration–time curve from time zero to infinity ratios were 0.94 and 1.06. Suvigletistat geometric mean elimination half‐life was comparable in Chinese (1.93 h), Japanese (2.23 h), and White/European participants (2.58 h). There were no serious adverse events or deaths. There were no clinically meaningful findings in laboratory values, vital signs, or electrocardiograms. No clinically meaningful differences in suvigletistat PK were observed between ancestry groups, providing evidence of low ethnic sensitivity for a drug with cytochrome P450 3A4‐dependent metabolism.
Abstract We conducted a pharmacokinetic study to compare two fixed‐dose combinations of ibuprofen/acetaminophen (IP‐TA and IP‐TB) with different formulation designs and excipient compositions, and explored how formulation differences influence ibuprofen pharmacokinetics by comparing in vitro dissolution and in vivo absorption profiles. In an open‐label, randomized, 2‐treatment, 2‐period, 2‐sequence crossover study, 24 healthy Japanese participants received a single oral dose of IP‐TA (ibuprofen 195 mg and acetaminophen 195 mg) or IP‐TB (ibuprofen 160 mg and acetaminophen 160 mg) under fasting conditions. Pharmacokinetic data were analyzed using a linear mixed‐effects model. Fraction absorbed (F a ) was estimated using the Loo–Riegelman method, and ibuprofen dissolution was evaluated at pH 1.2, 4.0, and 6.8. The relationship between weighted mean dissolution rates (D) and F a was examined. Ibuprofen absorption from IP‐TA was faster than from IP‐TB, as reflected by higher C max and greater early exposure, and these differences remained after dose normalization. Dissolution profiles showed temporal similarity with absorption profiles, particularly for IP‐TA. Analysis of F a also suggested a relatively high degree of synchronization between ibuprofen and acetaminophen absorption in IP‐TA. These findings indicate that formulation‐dependent differences in dissolution behavior may influence early ibuprofen absorption, although further studies are needed to clarify the underlying mechanisms.
Abstract We evaluated food‐associated differences in clindamycin hydrochloride capsule exposure by pooling publicly available regulatory bioequivalence (BE) summaries from the Center for Drug Evaluation of the National Medical Products Administration in China. Fourteen candidate regulatory identifiers were reviewed; one 0.15‐g BE‐exempt record without analyzable pharmacokinetic (PK) data was excluded, leaving 13 records (ten 150 mg and three 300 mg). CYHB1901758 and CYHB2140526 were treated as independent 300‐mg BE records under the authors’ prespecified working assumption. For each record and endpoint, test and reference formulation fed/fasted ratios were combined on the log scale, and regulatory records were pooled with equal weight. For the 150‐mg strength, pooled fed/fasted geometric mean ratios (GMRs) [95% descriptive interval] were 1.31 [1.24, 1.38] for AUC 0–t , 1.30 [1.23, 1.38] for AUC 0–inf , and 0.85 [0.80, 0.90] for C max . For the 300‐mg strength, the corresponding GMRs were 1.17 [0.92, 1.50], 1.19 [0.93, 1.52], and 0.93 [0.88, 0.97]. Thus, the available aggregate summaries showed higher total exposure and lower peak concentration under fed conditions, particularly for the 150‐mg strength. These findings describe a food‐associated PK pattern but do not constitute a formal regulatory food‐effect assessment or support a change in meal‐timing recommendations.
