Clinical Pharmacology in Drug Development最新文献

{"title":"Assessment of Pharmacokinetic Interaction and Clinical Efficacy of Clopidogrel Co-administered with Ilaprazole","authors":"Damodharan N,&nbsp;Priyadharshini A,&nbsp;Vijayakumar T M,&nbsp;Rajesh N A","doi":"10.1002/cpdd.70095","DOIUrl":"https://doi.org/10.1002/cpdd.70095","url":null,"abstract":"<p>Clopidogrel is often co-prescribed with proton pump inhibitors (PPIs) to reduce gastrointestinal bleeding risk. However, some PPIs, especially pantoprazole, inhibit CYP2C19, potentially reducing clopidogrel's activation. Ilaprazole, a newer PPI primarily metabolized via CYP3A4, may offer reduced interaction. The study was an open-label, randomized trial that involved 36 healthy male volunteers, who were divided into three groups (n = 12 each): Group 1 (Clopidogrel + Placebo), Group 2 (Clopidogrel + Pantoprazole 40 mg), and Group 3 (Clopidogrel + Ilaprazole 10 mg). After 7 days of treatment, all participants received clopidogrel 75 mg on Day 8. Pharmacokinetic (PK) parameters were analyzed using LC-MS/MS and platelet aggregation by light transmission aggregometry at 0, 4, 10, and 24 h. Pantoprazole significantly reduced clopidogrel AUC (1.96 ± 0.20 vs 8.27 ± 1.04 ng·h/mL, <i>P</i> &lt; .0005), C_max (0.76 ± 0.04 vs 2.6 ± 1.01 ng/mL, <i>P</i> = .0136), and t₁/₂ (1.72 ± 0.11 vs 2.22 ± 0.17 h, <i>P</i> = .0312), indicating reduced bioavailability. Geometric mean ratio (GMR) analysis showed a marked reduction in clopidogrel exposure with pantoprazole (C_max GMR 0.31, 90% CI 0.18–0.53; AUC GMR 0.24, 90% CI 0.19–0.29), and platelet aggregation was significantly higher at 4 and 10 h (<i>P</i> &lt; .05). In contrast, ilaprazole preserved PK parameters (AUC 10.18 ± 1.41, C_max 3.06 ± 1.05), GMRs near unity (C_max 1.20, 90% CI 0.60–2.42; AUC 1.23, 90% CI 0.97–1.55), indicating no inhibitory effect and platelet inhibition comparable to placebo (<i>P</i> &gt; .05) Ilaprazole did not affect clopidogrel pharmacokinetics or pharmacodynamics, suggesting it as a safer alternative to pantoprazole in dual antiplatelet therapy.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence Study of Two Ibuprofen Arginine Formulations in Healthy Chinese Subjects Under Fed Conditions","authors":"Yiyang Ying,&nbsp;Chunqi Huang,&nbsp;Li Xu,&nbsp;Yi Wu,&nbsp;Shufan Cai,&nbsp;Lijun Ye,&nbsp;Xiangxin Huang,&nbsp;Lin Wang,&nbsp;Ying Wang","doi":"10.1002/cpdd.70083","DOIUrl":"10.1002/cpdd.70083","url":null,"abstract":"<p>To evaluate the bioequivalence and safety of a generic ibuprofen arginine formulation (T) compared to Sibide (R) in healthy Chinese subjects under fed conditions, a randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted. Twenty-eight eligible healthy subjects received a single 400 mg dose of either the T or R formulation following a standardized high-fat meal, with a 3-day washout period between doses. Plasma ibuprofen concentrations were quantified using a validated LC-MS/MS method. Pharmacokinetic parameters, including C_max, AUC_0–t, and AUC_0–∞, were calculated using non-compartmental analysis. Bioequivalence was assessed based on the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) derived from ANOVA. All 28 enrolled subjects completed the study. The GMRs (90% CIs) for C_max, AUC_0–t, and AUC_0–∞ were 107.03% (100.02%–114.52%), 100.99% (98.46%–103.58%), and 100.95% (98.24%–103.74%), respectively. All 90% CIs fell entirely within the regulatory bioequivalence acceptance range of 0.80–1.25. Both formulations were well tolerated; adverse events were mild to moderate, and no serious adverse events were reported. Thus, the T formulation of ibuprofen arginine demonstrated bioequivalence to the R formulation in healthy Chinese subjects under fed conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure–Response Relationship of Dostarlimab in Primary Advanced/Recurrent Endometrial Cancer: Results From Interim Analysis 2 of Part 1 of the RUBY Trial","authors":"Mita Kuchimanchi,&nbsp;Trine Lembrecht Jørgensen,&nbsp;Eva Hanze,&nbsp;Angela Jain,&nbsp;Oskar Alskär,&nbsp;Oleksandr Zub,&nbsp;Mark S. Shahin,&nbsp;Anthoula Koliadi,&nbsp;Bhavana Pothuri,&nbsp;Thomas Krivak,&nbsp;Mikalai Pishchyk,&nbsp;Yakir Segev,&nbsp;Floor J. Backes,&nbsp;Christine Gennigens,&nbsp;Sara Bouberhan,&nbsp;Stefan Zajic,&nbsp;Murad Melhem,&nbsp;Joseph Buscema","doi":"10.1002/cpdd.70087","DOIUrl":"10.1002/cpdd.70087","url":null,"abstract":"<p>Dostarlimab in combination with carboplatin–paclitaxel was approved for primary advanced or recurrent endometrial cancer (pA/rEC). The first interim analysis (IA1) of RUBY Part 1 (NCT03981796) showed no significant exposure–response (ER) relationship for progression-free survival or for the five most common dostarlimab-related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab-related AEs. Population pharmacokinetic model was based on IA1, and the predicted exposure metrics from Cycle 1 were used to perform ER analysis at the second interim analysis (IA2). AE analysis was completed for three periods: Cycles 1-6 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin–paclitaxel. Cox regression of OS showed no significant ER relationship based on dostarlimab Cycle 1 exposure, except for rash and arthralgia. The increase in predicted probabilities for rash and arthralgia for patients with high versus low exposure was limited, ranging from 5.6% to 10.4% for rash and 4.3% to 17.7% for arthralgia (deemed not clinically relevant). These data support the risk/benefit profile at the selected dose of dostarlimab + carboplatin–paclitaxel as standard of care in patients with pA/rEC.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distributed Manufacturing, Foreign Establishments, and Why the FDA's New Proposed Rule Matters to Clinical Pharmacology","authors":"Amalia M. Issa PhD, MPH, FCP","doi":"10.1002/cpdd.70088","DOIUrl":"10.1002/cpdd.70088","url":null,"abstract":"&lt;p&gt;On July 13, 2026, the United States Food and Drug Administration (FDA) published a proposed rule amending 21 CFR Part 207, the drug establishment registration and listing regulations.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The rule does two things. First, it creates a new registration pathway for “distributed manufacturing establishments” (DMEs). DMEs are basically hub-and-spoke operations in which a single quality unit oversees distributed manufacturing units (DMUs) that can be added, removed, or physically relocated across multiple sites, potentially in different countries, without each one requiring a separate registration. Second, it aligns FDA's foreign establishment registration and listing requirements with the PREVENT Pandemics Act, closing a gap in which an active pharmaceutical ingredient (API) manufacturer that shipped only to other foreign sites had, in practice, remained invisible to the Agency even when its material eventually reached the United States as finished product.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This rule warrants the attention of our readers, not only those in Chemistry, Manufacturing, and Controls (CMC) and regulatory affairs but also clinical pharmacologists more generally, given its broader implications for the field. The FDA is accepting comments on the proposed rule through September 11, 2026.&lt;/p&gt;&lt;p&gt;Distributed manufacturing has been building toward this moment since the FDA named it a priority technology under its Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) initiative, followed by a 2022 discussion paper, a public workshop, and a 2023 stakeholder action plan.&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; The appeal is real: mobile or geographically distributed units that are “equivalent in design and operation” can be surged to where demand exists, which matters for shortage-prone sterile injectables, cell and gene therapy starting materials, and emergency countermeasures.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Critically, the proposed rule does not require DMUs to be identical, only equivalent. The FDA deliberately leaves the concept of “equivalent” in this context open for the field to help calibrate.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;That is where clinical pharmacology has a stake. We have long owned the question of what counts as pharmacokinetically indistinguishable when something about how a product is made changes. Distributed manufacturing pushes that question into a more dynamic setting: not whether a post-approval site changed, but whether a unit that relocated last month still behaves, in vivo, like the sibling unit that never moved. FDA's own preamble flags this directly, noting that relocation introduces independent factors such as climate, utilities, or local conditions that could affect a unit's equivalence, and that this equivalence “would need to be evaluated and confirmed prior to manufacturing at the new location and through continued validation and monitoring.”&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; For products in early clinical development","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Open-Label, Balanced, Randomized, Single-Dose, Three-Treatment, Three-Sequence, Three-Period, Three-Way Crossover Oral Bioequivalence Study of Desmopressin Acetate Oral Solution","authors":"Adam Christensen,&nbsp;Axay Parth,&nbsp;Mansi Kotak,&nbsp;Danka Radosavjevic,&nbsp;Catherine Gorman Moore,&nbsp;Byung-Woun Seo","doi":"10.1002/cpdd.70086","DOIUrl":"10.1002/cpdd.70086","url":null,"abstract":"<p>Desmopressin is first-line therapy for central diabetes insipidus, also known as arginine vasopressin deficiency, but presents dosing challenges due to its narrow therapeutic index. This open-label, randomized, three-way crossover study evaluated the bioequivalence of a new desmopressin acetate oral solution (50 mcg/mL) compared to desmopressin acetate tablets (200 mcg) in 75 healthy adults. In a balanced, three-sequence, three-period design with 14-day washout periods, participants received a single 600-mcg dose of test product and reference product under fasted conditions. Plasma desmopressin concentrations were measured using a validated liquid chromatography-electrospray ionization tandem mass spectrometry method, and primary pharmacokinetic parameters (maximum plasma concentration [C_max], area under the plasma concentration–time curve from time 0 to the last measurable concentration [AUC_0–t], AUC from time 0 extrapolated to infinity [AUC_0–∞]) were derived from resulting concentration–time profiles. Bioequivalence was assessed using analysis of variance on log-transformed parameters, with 90% confidence intervals (CIs) for geometric mean ratios 80%–125%. Results demonstrated bioequivalence between formulations, with geometric mean ratios of 101.9% (93.9%–110.5%) for C_max, 103.7% (94.8%–113.5%) for AUC_0–t, and 103.7% (94.9%–113.3%) for AUC_0–∞. Both formulations exhibited similar pharmacokinetic profiles with 1.0 h median time to maximum concentration, ∼3.6 h mean elimination half-life, and 30%–33% intrasubject variability. Five adverse events were reported by five participants (6.7%), including two cases of hyponatremia (reference group) and one case of vomiting (test group); all were mild to moderate and resolved completely. This study establishes bioequivalence between desmopressin acetate oral solution and tablets, supporting regulatory approval of the oral solution formulation.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, Pharmacokinetics, Food Effect of Ribitol, and Its Effect on QTcF in Healthy Adults: First-in-Human, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Studies","authors":"Daniel D. Gretler,&nbsp;Athiwat Hutchaleelaha,&nbsp;Uma Sinha,&nbsp;Kristen Rickert,&nbsp;Doug Sproule","doi":"10.1002/cpdd.70082","DOIUrl":"https://doi.org/10.1002/cpdd.70082","url":null,"abstract":"<p>Limb-girdle muscle dystrophy Type R9 (LGMDR9), also known as LGMD Type 2I, is a rare genetic disease caused by partial loss of function of fukutin-related protein (FKRP) enzyme which glycosylates alpha-dystroglycan, thereby stabilizing myocytes during contraction. Hypoglycosylation leads to progressive muscle injury and impaired function including loss of ambulation. Ribitol is an endogenous pentose alcohol and precursor to CDP-ribitol, the substrate of FKRP. This first-in-human study demonstrated that ribitol was well tolerated when administered as single or multiple oral doses over 6 days to healthy adults. PK demonstrated dose-proportional increases in exposure from 0.5 to 15 g (therapeutic dose 9 and 12 g BID for patients weighing &gt;30 to ≤50 kg and &gt;50 kg, respectively); t_½ was 9-13 h. A high-fat meal did not affect overall oral bioavailability; indicating ribitol may be taken without regard to food intake. A dedicated QT study using ribitol 21 g revealed no concentration-dependent QTcF prolongation and clinically significant QTcF prolongation was excluded over the entire range of exposures in the study, up to 351.9 µg/mL. Assay sensitivity was demonstrated with the expected effect of moxifloxacin. These results support further development of ribitol for the treatment of LGMDR9.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 1 Study of Paltusotine, a Novel Oral Once‑Daily, Nonpeptide Selective Somatostatin Receptor 2 Agonist, in Healthy Japanese Adults","authors":"Fumio Otsuka,&nbsp;Keiko Hanabara,&nbsp;Seigo Akari,&nbsp;Katsunori Kitamoto,&nbsp;Yosuke Inagaki,&nbsp;Dylan Glatt,&nbsp;Harumi Murakami,&nbsp;Naoki Uchida","doi":"10.1002/cpdd.70085","DOIUrl":"10.1002/cpdd.70085","url":null,"abstract":"<p>Paltusotine is a novel, nonpeptide, once-daily oral, selective somatostatin 2 receptor (SST2) agonist. We evaluated the pharmacokinetics, pharmacodynamics, and safety of oral paltusotine in healthy Japanese adults in single‑dose (20, 40, 60, 80 mg) and repeated‑dose (40 mg once daily for 7 days in a two-sequence, two‑period crossover design) studies. In addition, the effects of food intake and pharmacodynamics were examined in the repeated-dose study. Eight participants were enrolled in each dose of the single-dose study, and 12 participants were enrolled in the repeated-dose study. In both studies, there were no deaths, serious adverse events, or severe adverse events. In the single-dose study, plasma paltusotine exposures increased in a dose-dependent manner for the dose range of 20 to 80 mg (based on C_max and AUC_0-∞), and the elimination half-life (t_1/2) was 24-28 h. In the repeated-dose study, similar reductions from baseline in serum insulin-like growth factor-1 (IGF-I) were observed for 1-h pre-prandial (−60.1 ± 26.0 ng/mL) and 3-h post-prandial administration (−61.6 ± 17.7 ng/mL) on Day 7. Overall, this study establishes the pharmacokinetics, pharmacodynamics, and safety in healthy Japanese adults to support the development of paltusotine as a treatment for acromegaly and pituitary gigantism.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Bioequivalence Study of Levodopa and Benserazide Tablets in Healthy Chinese Subjects Under Fasting and High-Fat Meal Conditions","authors":"Yufei Liang,&nbsp;Yanchao Wang,&nbsp;Rui Shi,&nbsp;Yingzi Pei,&nbsp;Xiao Zhao,&nbsp;Qian Wang,&nbsp;Yanping Ren,&nbsp;Zekang Xie,&nbsp;Kexin Zhao","doi":"10.1002/cpdd.70080","DOIUrl":"10.1002/cpdd.70080","url":null,"abstract":"<p>Levodopa and benserazide tablets (LBTs) are a combined preparation of levodopa (L-DP), a dopamine precursor, and benserazide (BZ), a peripheral dopa decarboxylase inhibitor, used for the treatment of Parkinson's disease, which predominantly affects middle-aged and elderly individuals. This study employed a single-center, randomized, open-label, two-formulation, three-period, three-sequence, partially replicated (reference formulation only) clinical study design to evaluate the pharmacokinetics and bioequivalence of the test and reference formulations of LBT administered orally to 96 healthy Chinese subjects under fasting or fed conditions. After fasting for at least 10 h and abstaining from water for 1 h, subjects received one tablet of either the test or reference formulation with 240 mL of warm water on Days 1, 8, and 15 of the study, either in the fasting state or 30 min after starting a high-fat meal. Plasma drug concentrations were determined using an ultra-high performance liquid chromatography-tandem mass spectrometry method. The 90% confidence intervals of the geometric mean ratios for the pharmacokinetic parameters C_max, AUC_0-t, and AUC_0-∞ met the bioequivalence criteria, indicating that the test formulation is bioequivalent to the reference formulation in healthy Chinese adult subjects. No serious adverse events were reported.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative bioavailability of a novel fixed-dose combination of ticagrelor and acetylsalicylic acid","authors":"Susana Tera-Ponce,&nbsp;Perla E. Castañeda-Tera,&nbsp;Elva J. García-Real,&nbsp;Francisco Ávila-García,&nbsp;Kevin F. Rios-Brito,&nbsp;Laura A. Lugo-Sánchez,&nbsp;Daniel E. Sandoval-Colin,&nbsp;Paola M. Medina-Cárdenas,&nbsp;Jorge González-Canudas","doi":"10.1002/cpdd.70084","DOIUrl":"10.1002/cpdd.70084","url":null,"abstract":"<p>Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (hereafter referred to as ASA) and ticagrelor is the standard of care for secondary prevention for atherothrombotic events, particularly in patients with noncardioembolic cerebrovascular disease or coronary artery disease. However, prolonged DAPT requires multiple daily tablets, which can compromise adherence; a fixed-dose combination could reduce pill burden and improve treatment persistence. This study evaluated the comparative bioavailability of a fixed-dose combination (FDC) capsule of ticagrelor 90 mg/ASA 100 mg (test) versus the concomitant administration of ticagrelor 90 mg tablet plus ASA 100 mg tablet (reference) under fasting conditions in healthy Mexican volunteers. We applied a randomized, open-label, two-period crossover, single-dose design with a 7-day washout and quantified plasma concentrations by liquid chromatography-tandem mass spectrometry. Twenty-four subjects were enrolled. Geometric mean ratios (90% confidence intervals) for ticagrelor maximum plasma concentration and area under the plasma concentration-time curve from 0 to 48 h, were 111.5% (102.3–121.5), and 100.3% (93.4–107.7); for salicylic acid, 95.4% (90.1–100.9), and 101.5% (96.7–106.5). All 90% confidence intervals fell within the predefined 80–125% range, and both formulations were well tolerated. These findings support the FDC as an alternative that may simplify long-term DAPT for the secondary prevention of atherothrombotic events.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence of Two Firsekibart Subcutaneous Formulations: A Randomized, Double-Blind, Single-Dose, Parallel-Group Study in Healthy Chinese Participants","authors":"Yehua Xie,&nbsp;Xiao Li,&nbsp;Yushi Chen,&nbsp;Guangli Ma,&nbsp;Fei Gu,&nbsp;Yuling Lian,&nbsp;Xu Zhang,&nbsp;Xiaolan Yong","doi":"10.1002/cpdd.70077","DOIUrl":"10.1002/cpdd.70077","url":null,"abstract":"<p>We evaluated the pharmacokinetic (PK) bioequivalence and safety of a new formulation of firsekibart (solution for injection) compared with firsekibart lyophilized powder for solution. In this randomized, double-blind, parallel-group study, healthy Chinese adult males received a single subcutaneous dose of 200 mg firsekibart solution for injection (test product, T) or firsekibart powder for solution (reference product, R), followed through Day 141. The primary objective was to evaluate PK bioequivalence between T and R, concluded if least-squares geometric mean ratio (GMR) 90% confidence intervals (CIs) were within 80.00%–125.00%. Safety was also evaluated. A total of 181 participants received T (N = 90) or R (N = 91). PK profiles were comparable between T and R: least-squares GMRs (T/R; 90% CI) for the maximum serum concentration, area under the concentration–time curve (AUC) from time zero to the last time of quantifiable concentration, and AUC from time 0 to infinity were 104.26% (98.11%, 110.80%), 103.45% (98.15%, 109.04%), and 102.14% (96.75%, 107.83%), respectively. Most treatment-emergent adverse events were mild/moderate and generally comparable between T and R, with no treatment-related serious adverse events reported. Firsekibart solution for injection was bioequivalent to firsekibart lyophilized powder for solution for injection in healthy Chinese males, with no new safety signals identified.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}