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A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects

BACKGROUND: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety...

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Autores principales: Ma, Junlong, Huang, Jie, Zou, Chan, Wu, Qian, Xie, Jinlian, Zhang, Xingfei, Yang, Xiaoyan, Yang, Shuang, Wu, Ziteng, Jiang, Yan, Yu, Sen, Zhang, Xuqing, Yang, Guoping, Li, Mingyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406176/
https://www.ncbi.nlm.nih.gov/pubmed/37554228
http://dx.doi.org/10.2147/DDDT.S418730
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author Ma, Junlong
Huang, Jie
Zou, Chan
Wu, Qian
Xie, Jinlian
Zhang, Xingfei
Yang, Xiaoyan
Yang, Shuang
Wu, Ziteng
Jiang, Yan
Yu, Sen
Zhang, Xuqing
Yang, Guoping
Li, Mingyuan
author_facet Ma, Junlong
Huang, Jie
Zou, Chan
Wu, Qian
Xie, Jinlian
Zhang, Xingfei
Yang, Xiaoyan
Yang, Shuang
Wu, Ziteng
Jiang, Yan
Yu, Sen
Zhang, Xuqing
Yang, Guoping
Li, Mingyuan
author_sort Ma, Junlong
collection PubMed
description BACKGROUND: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects. METHODS: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg Mobic(Ⓡ) (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15–60 mg (C(max) and AUC(0-t) were 5.82–17.66 μg/mL and 58.08–251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference. CONCLUSION: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain. TRIAL REGISTRATION: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).
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spelling pubmed-104061762023-08-08 A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects Ma, Junlong Huang, Jie Zou, Chan Wu, Qian Xie, Jinlian Zhang, Xingfei Yang, Xiaoyan Yang, Shuang Wu, Ziteng Jiang, Yan Yu, Sen Zhang, Xuqing Yang, Guoping Li, Mingyuan Drug Des Devel Ther Original Research BACKGROUND: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects. METHODS: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg Mobic(Ⓡ) (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15–60 mg (C(max) and AUC(0-t) were 5.82–17.66 μg/mL and 58.08–251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference. CONCLUSION: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain. TRIAL REGISTRATION: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884). Dove 2023-08-03 /pmc/articles/PMC10406176/ /pubmed/37554228 http://dx.doi.org/10.2147/DDDT.S418730 Text en © 2023 Ma et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ma, Junlong
Huang, Jie
Zou, Chan
Wu, Qian
Xie, Jinlian
Zhang, Xingfei
Yang, Xiaoyan
Yang, Shuang
Wu, Ziteng
Jiang, Yan
Yu, Sen
Zhang, Xuqing
Yang, Guoping
Li, Mingyuan
A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title_full A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title_fullStr A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title_full_unstemmed A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title_short A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Intravenous Formulation of Meloxicam (QP001) in Healthy Chinese Subjects
title_sort phase i study to evaluate the safety, tolerability, and pharmacokinetics of novel intravenous formulation of meloxicam (qp001) in healthy chinese subjects
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406176/
https://www.ncbi.nlm.nih.gov/pubmed/37554228
http://dx.doi.org/10.2147/DDDT.S418730
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