Two-Part Phase 1 Study to Evaluate the Taste Profile of Novel Belumosudil Oral Suspensions and Assess the Relative Bioavailability and Food Effect of the Selected Belumosudil Oral Suspension Compared With Oral Tablet Reference in Healthy Male Participants

IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Clinical Pharmacology in Drug Development Pub Date : 2024-02-12 DOI:10.1002/cpdd.1378
Olivier Schueller, Galit Regev, Nand Singh, Ashley Willson, Mark Beville, Nazim Kanji, Lauren Lohmer, Jeegar Patel
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Abstract

Belumosudil is a selective rho-associated coiled-coil-containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft-versus-host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft-versus-host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension. Addition of sweetener and/or flavor vehicle improved the taste. Relative bioavailability of 200-mg doses of the oral suspension and tablet in the fed state was similar for belumosudil and its metabolites (KD025m1 and KD025m2), but absorption was faster with the oral suspension (median time to maximum concentration: 2 vs 3 hours). Administration of the oral suspension with food increased exposure compared with fasted administration, with maximum observed concentration being increased by 16% and area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) by 19%. Safety and tolerability were consistent with the known safety profile of belumosudil. These results may support administration of a 200-mg belumosudil oral suspension with or without food.

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由两部分组成的 1 期研究,旨在评估新型贝卢莫司地尔口服混悬液的口味特征,并评估选定贝卢莫司地尔口服混悬液与口服片剂参照物相比在健康男性参与者中的相对生物利用度和食物效应。
贝卢莫司地是一种选择性rho相关盘卷含蛋白激酶2抑制剂,临床上用于治疗慢性移植物抗宿主病。目前的片剂配方可能不适合有吞咽困难和/或慢性移植物抗宿主病上消化道表现的儿童或成人。本研究(NCT04735822)评估了贝鲁莫司地尔口服混悬液的口感和适口性,评估了口服混悬液与片剂的相对生物利用度,并描述了食物对口服混悬液药代动力学的影响。添加甜味剂和/或调味剂可改善口感。对于贝卢莫司地尔及其代谢物(KD025m1 和 KD025m2),200 毫克剂量的口服混悬液和片剂在进食状态下的相对生物利用度相似,但口服混悬液的吸收更快(达到最大浓度的中位时间:2 小时对 3 小时)。与空腹服用相比,进食后服用口服混悬液可增加暴露量,观察到的最大浓度增加了16%,从0时到最后可测量浓度的浓度时间曲线下面积(AUC0-last)增加了19%。安全性和耐受性符合贝卢莫司地的已知安全性特征。这些结果可能支持在进食或不进食的情况下服用200毫克贝卢莫司地口服混悬液。
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来源期刊
CiteScore
3.70
自引率
10.00%
发文量
154
期刊介绍: Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.
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