Clinical Pharmacology in Drug Development最新文献

{"title":"Effect of Renal Impairment on the Pharmacokinetics and Safety of Doxecitine and Doxribtimine: A Single-Dose Phase 1 Study","authors":"Aravind Mittur,&nbsp;Susan A. VanMeter","doi":"10.1002/cpdd.70036","DOIUrl":"10.1002/cpdd.70036","url":null,"abstract":"<p>This Phase 1 study investigated the pharmacokinetics and safety of a single dose of the FDA-approved doxecitine and doxribtimine (266.6 mg/kg; 133.3 mg/kg of deoxycytidine [dC] and deoxythymidine [dT]) in participants with severe (n = 8) or moderate (n = 8) renal impairment (estimated glomerular filtration rate [eGFR] 15–29 mL/min/1.73 m² and 30–59 mL/min/1.73 m², respectively) versus healthy matched controls (eGFR ≥90 mL/min/1.73 m²; n = 16 [two groups of eight]). Participants underwent serial sampling to determine total dC and dT plasma concentrations before (baseline) and after dosing (up to 96 h).</p><p>Participants with renal impairment had higher baseline-corrected dC and dT concentrations than controls, which peaked 0.75–1.5 h post-dose and declined to near baseline levels in ≤18 h. Geometric mean baseline-corrected plasma maximum concentration and area under the concentration–time curve (respectively) for dC and dT were higher in participants with severe (dC: 7.8 ng/mL and 52.8 h × ng/mL; dT: 18.8 ng/mL and 31.5 h × ng/mL) or moderate (dC: 8.2 ng/mL and 56.4 h × ng/mL; dT: 12.2 ng/mL and 23.7 h × ng/mL) renal impairment than in controls (dC: 4.6–5.3 ng/mL and 25.4–31.8 h × ng/mL; dT: 4.0–7.6 ng/mL and 4.3–12.7 h × ng/mL), with substantial variability. Geometric mean apparent terminal-phase half-lives in severe renal impairment, moderate renal impairment, and controls, respectively, were 14.5, 15.3, and 5.2–5.8 h for dC and 3.7, 4.5, and 0.4–1.5 h for dT. One participant experienced treatment-emergent adverse events (severe renal impairment cohort). In conclusion, renal impairment was associated with increased dC and dT exposure following a single dose of doxecitine and doxribtimine. No safety issues were identified.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194308","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":"Clinical Significance of IL-4 and IL-21 Concurrent Elevation in Predicting Disease Activity Score and Antihistamine Treatment Response in Chronic Spontaneous Urticaria","authors":"Shining Wang,&nbsp;Xiaojing Yang,&nbsp;Xuming Zhao,&nbsp;Leigang Chen,&nbsp;Jiayao Li,&nbsp;Guozhi An","doi":"10.1002/cpdd.70027","DOIUrl":"10.1002/cpdd.70027","url":null,"abstract":"<p>To investigate the predictive value of interleukin (IL)-4 and IL-21 levels in assessing disease activity score and antihistamine treatment response in chronic spontaneous urticaria (CSU) patients. One hundred and twenty CSU patients treated at our hospital between January 2023 and January 2025 were retrospectively selected as the study group. Eighty healthy individuals undergoing routine physical examinations during the same period were included as the control group. Serum IL-4 and IL-21 levels, and the proportion of peripheral blood follicular helper T (Tfh) cells within CD4⁺ T cells were retrieved from the hospital information system. Based on the Urticaria Activity Score over 7 days (UAS7), CSU patients were divided into three subgroups: mild (UAS7 &lt; 16, n = 43), moderate (UAS7 16-27, n = 52), and severe (UAS7 ≥ 28, n = 25). All patients received standard antihistamine therapy for 4 weeks. According to treatment response, patients were categorized into four groups: complete remission, marked improvement, partial remission, and no response. The correlations of IL-4, IL-21, and Tfh cell levels with disease severity were analyzed, and their predictive value for CSU diagnosis and antihistamine treatment response was evaluated. IL-4 and IL-21 are co-upregulated in CSU patients, and their levels increase with disease activity and are positively correlated with UAS7 score (r =\u0000.603, 0.314, <i>P</i> &lt;\u0000.001). These biomarkers have a certain reference value for diagnosis and severity assessment of CSU. Baseline levels of IL-4 and IL-21 may serve as predictive biomarkers for antihistamine treatment response, providing a potential reference for individualized treatment strategies.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131352","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":"A comparative pharmacokinetic evaluation of two aqueous progesterone 25 mg injections in healthy postmenopausal women under fasting conditions: An open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study","authors":"Noopur Vyas,&nbsp;Amaresh Chakra,&nbsp;Prashant Sarode,&nbsp;Shruti Dharmadhikari,&nbsp;Gaurav Puppalwar,&nbsp;Chintan Khandhedia,&nbsp;Amey Mane,&nbsp;Alpesh Goyani,&nbsp;Ajay Jaysingh Khopade","doi":"10.1002/cpdd.70025","DOIUrl":"10.1002/cpdd.70025","url":null,"abstract":"<p>The growing demand for assisted reproductive technology (ART) has increased the need for effective luteal phase support. Progesterone, essential for maintaining early pregnancy, is a critical component of ART. This open-label, balanced, randomized, two-treatment, crossover, single-dose study compared the bioequivalence of aqueous progesterone 25 mg injection (AqSusten^® [Test, Sun Pharma Laboratories Limited]), compared to the innovator's aqueous progesterone 25 mg injection (Lubion^® [Reference, IBSA Farmaceutici Italia Srl]), in healthy postmenopausal women under fasting conditions. Forty-eight subjects received either treatment in Period 1, followed by alternate treatment in Period 2, with a 14-day washout period. Pharmacokinetics (<i>C</i>_max, AUC_0–t, AUC_0-∞) and mean plasma concentration–time profiles were assessed. Forty-five subjects completed the study. Pharmacokinetic data for both products were comparable, with percentage ratios for AUC_0–t, AUC_0−∞, and <i>C</i>_max of 99.16%, 98.78%, and 103.36%, respectively, within the acceptable bioequivalence range of 80%-125%. Plasma concentration–time profiles were similar, and no serious adverse events were reported. Mild adverse events with Lubion^® included increased white blood cell count and blood glucose. AqSusten^® demonstrated bioequivalence to Lubion^® in healthy postmenopausal women under fasting conditions. Both formulations exhibited similar pharmacokinetic profiles, with favorable safety and tolerability, suggesting AqSusten^® as a viable alternative in ART treatments.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123931","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":"Pharmacokinetic Comparability of ABP 654, a Biosimilar to Ustekinumab, Administered Either via Prefilled Syringe or Autoinjector in Healthy Adults: Results from a Randomized, Open-Label, Parallel-Group Study","authors":"Vincent Chow,&nbsp;Peter J. Winkle,&nbsp;Daniel T. Mytych,&nbsp;Jia Cao,&nbsp;Carolina Barragan,&nbsp;Alexander Colbert,&nbsp;Shalini Gupta,&nbsp;Waldemar Radziszewski,&nbsp;Janet Franklin","doi":"10.1002/cpdd.70031","DOIUrl":"10.1002/cpdd.70031","url":null,"abstract":"<p>ABP 654, a biosimilar to ustekinumab reference product, is available in a prefilled syringe (PFS) for subcutaneous (SC) use. The ABP 654 autoinjector pen (AIP) has recently been developed with an aim to improve the injection experience for patients and caregivers. This study was designed to assess the similarity of pharmacokinetics (PK), safety, and immunogenicity of a 90-mg SC injection of ABP 654 administered via PFS or AIP in healthy volunteers. A total of 156 adults were randomized at a ratio of 1:1. PK bioequivalence was established between the PFS and AIP groups based on the 90% CIs of the geometric mean ratios for the primary PK endpoints of maximum observed serum concentration (C_max) and area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC_inf) being contained within the prespecified margin of 0.8 to 1.25. The frequency, type, and severity of adverse events as well as the incidence of antidrug antibodies were similar between the PFS and AIP groups. Overall, the results support a conclusion of PK bioequivalency as well as comparable safety and immunogenicity of ABP 654 administered via PFS and AIP.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12875155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123878","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":"The Importance of the Peer Review Process to Safeguard Scientific Integrity","authors":"Kenneth T. Moore","doi":"10.1002/cpdd.70032","DOIUrl":"10.1002/cpdd.70032","url":null,"abstract":"&lt;p&gt;In an era defined by information overload, limited time, and competing professional demands, the role of the peer reviewer often comes at the expense of personal or free time. Yet, despite these challenges, performing this role remains an essential contribution to maintaining trustworthy science. I realize as I write this, I'm also proclaiming “Do as I say, not as I do,” as I have fallen victim to continually declining requests to act as a peer reviewer because of an ever-increasing workload from my employer, or important commitments I have made to my family and friends. However, today, where misinformation about science and medicine spreads rapidly across social media platforms, where political agendas often distort evidence-based discourse, and where questionable ‘science’ circulates without scrutiny, the peer review process, more than ever, serves as a critical safeguard for ensuring the credibility and rigor of science. Thus, if one identifies as a proponent of the scientific method and values a logical, data driven, and evidence-based foundation for scientific and medical dialogue, then active participation as a peer reviewer is less of an option and more of an ethical and professional responsibility. We cannot passively stand by and watch the ongoing deterioration of public trust in the professions we devoted our lives to. Rather, we must collectively reaffirm our commitment to credible research and the mechanisms by which knowledge remains verifiable, reproducible, and transparent.&lt;/p&gt;&lt;p&gt;At its core, peer review is a process that brings scientific and medical manuscripts to evaluation by independent experts within the same field of study. This process helps to ensure that the research being published meets the standards of validity, originality, and methodological soundness, while also safeguarding ethical integrity.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; By filtering out research that doesn't meet these standards, the peer review process serves as a quality assurance mechanism that helps not only protect the academic record on the subject, but ultimately the public welfare.&lt;/p&gt;&lt;p&gt;Moreover, the peer review process plays an important role in advancing knowledge and fostering innovation. It can facilitate intellectual exchange by encouraging researchers to refine their methods, clarify findings or interpretations, question assumptions, and even explore potential new directions not previously considered.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In this way, peer review is more than just a gatekeeping function, it acts as a source of collaboration, accountability, and innovation that sustains the continuous evolution of science.&lt;/p&gt;&lt;p&gt;The integrity of this process depends fundamentally on the ethical conduct and professional responsibility of reviewers. Reviewers must approach their task with impartiality, confidentiality, and respect for the intellectual property of others. Declaring conflicts of interest, whether financial, personal, or professional, is not merely a f","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123964","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":"What Makes an Early-Phase Study Worth Publishing? A View from the Editor's Desk","authors":"Amalia M. Issa","doi":"10.1002/cpdd.70026","DOIUrl":"10.1002/cpdd.70026","url":null,"abstract":"&lt;p&gt;As we are now in the first quarter of 2026, with renewed strategic plans and operational goals across pharmaceutical clinical pharmacology functions, it is worth pausing to reflect on a central question that many clinical pharmacologists confront repeatedly: &lt;b&gt;what makes an early-phase study worth publishing?&lt;/b&gt; In an era where accelerated timelines, complex modalities, and model-informed approaches challenge traditional development paradigms, this is an opportune moment to clarify the editorial value for &lt;i&gt;Clinical Pharmacology in Drug Development&lt;/i&gt; of early-phase study reporting and advance community expectations accordingly.&lt;/p&gt;&lt;p&gt;Early-phase studies, whether first-in-human (FIH), dose–range explorations, or integrated pharmacokinetic/pharmacodynamic (PK/PD) and biomarker investigations, are not merely organizational milestones on the path to registrational decision points. They are critical generators of knowledge that inform dose selection, safety profiling, translational hypotheses, and risk mitigation strategies. Yet, despite their central role in decision making, early-phase studies are generally under-reported in the peer-reviewed literature or published only selectively, particularly when results are neutral or do not lead to further development. This practice diminishes community learning and can slow the cumulative scientific progress that clinical pharmacologists seek to achieve.&lt;/p&gt;&lt;p&gt;These criteria align with broader scientific values including rigorous methods, transparent reporting, and clear impact on drug development. Manuscripts that thoughtfully explain both what was learned and what remains uncertain serve the industry and regulators alike.&lt;/p&gt;&lt;p&gt;Regulatory expectations underscore that early-phase data are not transient artifacts of internal decision making; they are evidence that shapes dose rationale, informs benefit–risk assessments, and supports labeling claims. Journals provide the conduit by which these data enter the public scientific domain, enabling cross-program rationalization and cumulative learning.&lt;/p&gt;&lt;p&gt;As we advance through 2026, we encourage clinical pharmacologists to approach manuscript preparation proactively. Early consideration of publication beginning at protocol design can shape data collection, endpoint selection, and analysis strategies that enhance both regulatory readiness and scientific value.&lt;/p&gt;&lt;p&gt;Publication is not merely an academic exercise; it is a strategic contribution to the discipline of clinical pharmacology, informing how early-phase insights translate into safer, more efficacious therapies. When a study meaningfully informs a decision, extends understanding, or helps others avoid pitfalls, it deserves to be part of the published record.&lt;/p&gt;&lt;p&gt;Ultimately, our goal is to build a cumulative, transparent, and actionable body of evidence that advances clinical pharmacology and accelerates the delivery of better medicines to patients worldwide.&lt;/p&gt;&lt;p&gt;AMI declares no conflict of int","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123903","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 and Pharmacokinetic Evaluation of Gliclazide Modified-Release Tablets in Healthy Chinese Volunteers","authors":"Kejia Fu,&nbsp;Chengcan Lu,&nbsp;Yuping Zhang,&nbsp;He Pan,&nbsp;Zhaoyu Wang,&nbsp;Xijing Chen,&nbsp;Yi Liang","doi":"10.1002/cpdd.70021","DOIUrl":"10.1002/cpdd.70021","url":null,"abstract":"<p>This was a single-center, randomized, open-label, two-formulation, and two-cycle crossover trial conducted in 52 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (gliclazide modified-release tablets) and reference formulation (30 mg) during each study period. Blood samples were collected before and up to 72 h after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios (GMRs) of C_max, AUC_0–t, and AUC_0–∞ for gliclazide were as follows: 93.9%, 99.2%, and 101.8%, respectively (under fasting conditions); 99.0%, 94.6%, and 98.8%, respectively (under fed conditions). The 90% confidence intervals for the GMRs were within the 80%–125% equivalence interval for both the fasting and fed tests. Ingesting high-fat and high-calorie foods accelerate the absorption rate of gliclazide, does not meaningfully alter the extent of absorption. The safety profiles of the two preparations were similar.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123898","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 Evaluation of Two Metformin/Empagliflozin Fixed-Dose Combination Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions: A Randomized, Open-Label, Crossover Study","authors":"Yuyan Lei,&nbsp;Qin Yi,&nbsp;Shan Ji,&nbsp;Juli Lu,&nbsp;Zhenya Yang","doi":"10.1002/cpdd.70029","DOIUrl":"10.1002/cpdd.70029","url":null,"abstract":"<p>This study evaluated the bioequivalence and safety of two fixed-dose combination (FDC) tablet formulations of metformin/empagliflozin (1000 mg/5 mg) in healthy Chinese subjects. A single-center, open-label, randomized, two-period, two-treatment, and two-sequence crossover study was conducted, enrolling 56 subjects who were assigned to either fasting or fed conditions in a 1:1 ratio. Each subject received both the test and reference formulations, with a 7-day washout period between administrations. Blood samples were collected up to 48 h post-dose, and plasma concentrations of metformin and empagliflozin were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Bioequivalence was assessed based on key pharmacokinetic parameters—C_max, AUC_0–t, and AUC_0–∞—with the geometric least-squares mean ratios of the test to reference formulation falling within the accepted bioequivalence range of 80.00% to 125.00% for all 90% confidence intervals under both fasting and fed states. High-fat meals significantly reduced the C_max of metformin and empagliflozin by approximately 47% and 28%, respectively, and their overall exposure (AUC_0−∞) by approximately 29% and 15%, respectively. No serious adverse events were reported. In conclusion, the test and reference formulations of metformin/empagliflozin FDC tablets were bioequivalent and well-tolerated under both fasting and fed conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040657","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":"A Human Mass Balance and Metabolism Study of [14C]-Ubrogepant in Healthy Male Adults","authors":"Ramesh R. Boinpally,&nbsp;Joshua Rowe,&nbsp;Pushpa Chandrasekar,&nbsp;Rebecca B. White,&nbsp;Eugene E. Marcantonio,&nbsp;Nicole Trainor,&nbsp;Yuexia Liang,&nbsp;Cheri Maciolek,&nbsp;James H. Small,&nbsp;Robert Houle,&nbsp;Michael J. Hafey,&nbsp;Huizhi Xie,&nbsp;Jocelyn Yabut,&nbsp;Christine Fandozzi","doi":"10.1002/cpdd.70010","DOIUrl":"10.1002/cpdd.70010","url":null,"abstract":"<p>Ubrogepant is a calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine with or without aura in adults. The mass balance and metabolism of ubrogepant was evaluated in six healthy male adults administered a single oral dose of [¹⁴C]-ubrogepant 50 mg (∼200 µCi). Overall, the mean total radioactivity recovery was 92.4% (95% CI: 77.8%-107%) of the administered dose, with 82.9% in feces (95% CI: 66.7%-99.1%) and 9.52% in urine (95% CI: 7.78%-11.3%). Ubrogepant was eliminated mainly via metabolism, primarily via biliary/fecal excretion. Approximately 42% and 6% of the dose was excreted as unchanged parent drug in feces and urine, respectively. The major circulating components of drug-related material (DRM) in pooled plasma samples were ubrogepant (55%), M15 (13%), and M20 (3.5%). M15 (glucuronide of methylated catechol) and M20 (glucuronide of mono-oxygenated ubrogepant [M8]) also were the main metabolites in urine, together representing about 2% of DRM. In feces, the main metabolites were the oxidative metabolites M6 (di-oxygenated ubrogepant) and M8, together representing about 29% of DRM. In vitro assays showed that ubrogepant metabolism occurs predominantly via CYP3A4.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009286","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":"First-In-Human Study to Assess the Pharmacokinetics and Safety of DS-6016a After Single Subcutaneous Injection in Healthy Japanese Adults","authors":"Kei Okita,&nbsp;Hidetoshi Furuie,&nbsp;Akifumi Kurata,&nbsp;Yasuko Owada,&nbsp;Satoshi Yoshiba,&nbsp;Kei Furihata,&nbsp;Takaaki Oka,&nbsp;Yushi Kashihara,&nbsp;Hitoshi Ishizuka,&nbsp;Kazutaka Yoshihara","doi":"10.1002/cpdd.70023","DOIUrl":"10.1002/cpdd.70023","url":null,"abstract":"<p>Fibrodysplasia ossificans progressiva is a rare, progressive autosomal dominant genetic disease caused by an activin receptor-like kinase 2 (ALK2) mutation with a need for effective prophylactic therapies. This single-center, randomized, double-blind, placebo-controlled study evaluated the pharmacokinetics and safety of DS-6016a, a novel humanized monoclonal anti-ALK2 antibody, in healthy Japanese adults. In each of the 5–1000 mg DS-6016a or placebo single subcutaneous dose cohorts, eight male participants were randomly assigned at a 3:1 ratio. DS-6016a had median times to maximum plasma concentration of 144–240 h and elimination half-lives of 391–844 h. The increase in DS-6016a exposure was greater than dose-proportional across the dose range of 5–1000 mg. The incidence of study drug-related treatment-emergent adverse events (TEAEs) was 17% in the placebo group and 11% across all DS-6016a groups; all were mild and resolved without treatment. No deaths, serious or severe TEAEs, or TEAEs leading to study discontinuation were reported. Ferritin showed a statistically significant dose-dependent decrease from baseline, while serum iron showed no clear dose-dependency. No relationship was observed between DS-6016a dose and the development of anti-drug antibodies. DS-6016a had an acceptable safety profile at single subcutaneous doses of 5–1000 mg.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009305","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}