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Safety, Tolerability, and Pharmacokinetics of Single‐ and Multiple‐Ascending Doses of Sunobinop in Healthy Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-13 Alessandra Cipriano, Ram P. Kapil, Mingyan Zhou, Manjunath S. Shet, Garth T. Whiteside, Sandra K. Willsie, Stephen C. Harris
Sunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single‐ and multiple‐dose administration of sunobinop in healthy participants. Study 1 was a randomized, double‐blind, placebo‐controlled, single‐ascending dose study
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Comparative Bioequivalence and Food Effect of Two Formulations of 30‐mg Nifedipine Controlled‐Release Tablets in Healthy Chinese Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-13 Huizi Zhang, Siyang Wang, Hongxia Wang, Tingting Zhi, Jian Ren, Yanhui Wang, Zhiqing Yao, Pan Zhang, Naobei Ye, Ruiqin Zhang
Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30‐mg nifedipine controlled‐release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open‐label, randomized, single‐dose, crossover studies were conducted, 1 under fasting conditions (N =
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Pharmacokinetic and Safety Comparison of Fixed‐Dose Combination of Cilostazol/Rosuvastatin (200 + 20 mg) Versus Concurrent Administration of the Separate Components in Healthy Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-12 Jae Hoon Kim, Jang Hee Hong, Jin‐Gyu Jung, Won Tae Jung, Kyu‐Yeol Nam, Jae Seok Roh, Youn Woong Choi, Junbae Bang, Hyunwook Huh, Hye J. Lee, JungHa Moon, Jaehee Kim, Jung Sunwoo
The combined cilostazol and rosuvastatin therapy is frequently used for coronary artery disease treatment. This open‐label, 3 × 3 crossover clinical trial evaluated the pharmacokinetics and safety of a fixed‐dose combination (FDC) of cilostazol/rosuvastatin (200 + 20 mg) versus a concurrent administration of the separate components (SCs) under both fasted and fed conditions. Among 48 enrolled healthy
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Nlmixr2 Versus NONMEM: An Evaluation of Maximum A Posteriori Bayesian Estimates Following External Evaluation of Gentamicin and Tobramycin Population Pharmacokinetic Models Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-11 Alexandre Duong, Amélie Marsot
The objective of this project is to compare the results of the same study carried out on NONMEM and nlmixr2. This analysis consists of evaluating previously published population pharmacokinetic models of gentamicin and tobramycin in our population of interest with sparse concentrations. A literature review was performed to determine the gentamicin and tobramycin models in critically ill adult patients
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Cardiovascular Evaluation of Etrasimod, a Selective Sphingosine 1‐phosphate Receptor Modulator, in Healthy Adults: Results of a Randomized, Thorough QT/QTc Study Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-05 Borje Darpo, Kalvin Connor, Christopher H. Cabell, John S. Grundy
Etrasimod is an investigational, once‐daily, oral, selective sphingosine 1‐phosphate receptor 1,4,5 modulator used as an oral treatment option for immune‐mediated inflammatory disorders. This randomized, double‐blind, placebo‐ and positive‐controlled, parallel‐group, healthy adult study investigated etrasimod's effect on the QT interval and other electrocardiogram parameters. All participants received
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Pharmacokinetic Evaluation of the CYP3A4 and CYP2C9 Drug‐Drug Interaction of Avacopan in 2 Open‐Label Studies in Healthy Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-03-01 Shichang Miao, Pirow Bekker, Danielle Armas, Mary Lor, Yanyan Han, Kenneth Webster, Ashit Trivedi
Avacopan, a complement 5a receptor (C5aR) antagonist approved for treating severe active antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis, was evaluated in 2 clinical drug‐drug interaction studies. The studies assessed the impact of avacopan on the pharmacokinetics (PK) of CYP3A4 substrates midazolam and simvastatin and CYP2C9 substrate celecoxib, and the influence of CYP3A4 inhibitor
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Effect of Strong CYP3A4 Inhibition, CYP3A4 Induction, and OATP1B1/3 Inhibition on the Pharmacokinetics of a Single Oral Dose of Sotorasib Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-29 Panli Cardona, Sandeep Dutta, Brett Houk
Sotorasib is a small molecule that irreversibly inhibits the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein with a G12C amino acid substitution mutant protein. The impact of cytochrome P450 (CYP) 3A4 inhibition and induction on sotorasib pharmacokinetics (PKs) was evaluated in 2 separate studies in healthy volunteers (N = 14/study). The impact of CYP3A4 inhibition was interrogated utilizing
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Pharmacokinetics, Safety, and Tolerability of Cedirogant in Healthy Japanese and Chinese Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-27 Mohamed‐Eslam F Mohamed, Yuli Qian, Ronilda D'Cunha, Shuai Hao, Roberto Carcereri De Prati, Gweneth F Levy, Kinjal Hew, Wei Liu
Cedirogant is an inverse agonist of retinoic acid‐related orphan receptor gamma, thymus (RORγt) developed for treatment of psoriasis. This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in healthy Japanese
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Physiologically Based Pharmacokinetic Absorption Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-23 Shintaro Nakayama, Viera Lukacova, Shuichi Tanabe, Akiko Watanabe, Jim Mullin, Sandra Suarez-Sharp, Takako Shimizu
Pexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high-fat meal (HFM) or low-fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250 mg orally twice daily with
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Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-23 Yumin Li, Zhen Zhang, Jizhen Xie, Xianghua Lian, Guangtao Zhang, Cheng Wang
This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single-center, 2-period, 2-sequence, randomized, open-label, self-crossover study with a washout period of 14 days, 30 in the
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Bioequivalence Between a New Omalizumab Prefilled Syringe With an Autoinjector or with a Needle Safety Device Compared with the Current Prefilled Syringe: A Randomized Controlled Trial in Healthy Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-23 Ramachandra Sangana, Yan Xu, Bharti Shah, Xianbin Tian, Julia Zack, Kasra Shakeri‐Nejad, Sampath Kalluri, Ieuan Jones, Monica Ligueros‐Saylan, Angel Fowler Taylor, Devendra Kumar Jain, Emil Scosyrev, Alkaz Uddin, Nathalie Laurent, Paola Paganoni
Omalizumab is an anti‐IgE monoclonal antibody currently approved for the treatment of asthma, nasal polyps/chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria. Omalizumab is available as an injection in a prefilled syringe (PFS) with a needle safety device (NSD). New product configurations were developed to reduce the number of injections per dose administration, improve patient
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Phase 1 Healthy Volunteer Study of AL01211, an Oral, Non-brain Penetrant Glucosylceramide Synthase Inhibitor, to Treat Fabry Disease and Type 1 Gaucher Disease Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-16 Michael Babcock, Jianhong Zheng, Jessica Gail Shurr, Li Li, Bing Wang, Pedro Huertas, Philip John Ryan, Yuqiao Shen, Marvin Garovoy
Glycosphingolipid (GSL) storage diseases are caused by deficiencies in the enzymes that metabolize different GSLs in the lysosome. Glucosylceramide synthase (GCS) inhibitors reduce GSL production and have potential to treat multiple GSL storage diseases. AL01211 is a potent, oral GCS inhibitor being developed for the treatment of Type 1 Gaucher disease and Fabry disease. AL01211 has minimal central
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Evaluation of the Effects of Meal Type and Acid-Reducing Agents on the Pharmacokinetics of Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-12 Elijah J. Weber, Islam R. Younis, Lulu Wang, Deqing Xiao, William T. Barchuk, Ahmed A. Othman
Cilofexor is a nonsteroidal farnesoid X receptor agonist being developed in combination with firsocostat/semaglutide for the treatment of nonalcoholic steatohepatitis. This phase 1 study evaluated the effects of food and acid-reducing agents (ARAs) on the pharmacokinetics of cilofexor (100- or 30-mg fixed-dose combination with firsocostat) in healthy participants. Cohorts 1 (n = 20, 100 mg) and 2 (n
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Safety, Pharmacokinetics, and Pharmacodynamics of Etrasimod: Single and Multiple Ascending Dose Studies in Healthy Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-12 Caroline A. Lee, Stefan Schreiber, Brian Bressler, John W. Adams, Dooman Alexander Oh, Yong Q. Tang, Jinkun Zhang, Heather Kiyomi Komori, John S. Grundy
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator in development for immune-mediated inflammatory diseases (IMIDs). Here, we report the human safety, pharmacokinetics, and pharmacodynamics of etrasimod obtained from both a single ascending dose (SAD; 0.1-5 mg) study and a multiple ascending dose (MAD; 0.35-3 mg once daily) study. Overall,
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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 Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-12 Olivier Schueller, Galit Regev, Nand Singh, Ashley Willson, Mark Beville, Nazim Kanji, Lauren Lohmer, Jeegar Patel
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
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Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-07 Kuan-Ju Lin, Kenneth C. Turner, Hazem E. Hassan, Lutz O. Harnisch, John D. Davis, Albert Thomas DiCioccio
Osteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti-nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA-related pain, among other conditions. Data from 12 Phase I-III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab
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Safety, Tolerability, and Pharmacokinetics of Voriconazole for Injection in Two Preparations in Chinese Healthy Adult Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-07 Jin Yu, Yi Wu, Sisi Lin, Ying Wang
Voriconazole is a second-generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200 mg) manufactured by at a dose of 6 mg/kg in Chinese healthy adult volunteers. This was a single-center, randomized, open, 2-preparation, single-dose, 2-period, 2-sequence, crossover
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Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast-Acting, Nondihydropyridine Calcium Channel Blocker Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-05 James E. Ip, Douglas Wight, Corinne Seng Yue, David Nguyen, Francis Plat, Bruce S. Stambler
Etripamil, a fast-acting nondihydropyridine L-type calcium channel blocker, is under investigation for potential self-administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study
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Results from a Phase 1 Study Assessing the Pharmacokinetics of the Aldosterone Synthase Inhibitor Baxdrostat in Participants with Varying Degrees of Renal Function Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-02-04 Mason W. Freeman, Yuan-Di Halvorsen, Mary Bond, Brian Murphy, Jonathan Isaacsohn
Baxdrostat is a selective small-molecule aldosterone synthase inhibitor in development for treatment of hypertension and chronic kidney disease. This phase 1, open-label, parallel-group study assessed the safety and pharmacokinetics (PK) of baxdrostat in participants with varying degrees of renal function. Participants were enrolled into control (estimated glomerular filtration rate [eGFR] ≥60 mL/min)
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Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-29 Junyuan Qi, Ilseung Choi, Shuichi Ota, Satoshi Ichikawa, Naohito Fujishima, Hiroatsu Iida, Isamu Sugiura, Koichi Sugiura, Yasuharu Murata, Hiroyuki Inoue, Shoichi Ohwada, Jianxiang Wang
Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety
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Concentration-QTcF Modeling of Icenticaftor from a Randomized, Placebo- and Positive-Controlled Thorough QT Study in Healthy Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-29 Ganesh R. Iyer, Borje Darpo, Hongqi Xue, Jean Lecot, Julia Zack, Lidiya Bebrevska, Wendy Weis, Ieuan Jones, Anton Drollmann
Icenticaftor (QBW251) is a potentiator of the cystic fibrosis transmembrane receptor. Based on its mechanism of action, icenticaftor is expected to provide benefits in patients with chronic obstructive pulmonary disease by restoring mucociliary clearance, which would eventually lead to a reduction of bacterial colonization and related inflammatory cascade. A placebo- and positive-controlled, 4-way
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Comment on: Can Intranasal Nalmefene Reduce the Number of Opioid Overdose Deaths? Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-30 Phil Skolnick
With an emphasis on the disappointing limited impact of naloxone in reducing opioid overdose deaths, Sellers and Romach1 raise a number of compelling arguments. Their view is supported by data from the Centers for Disease Control and Prevention: According to the State Unintentional Drug Overdose Reporting System database, naloxone had been administered in more than 20% of opioid-related overdose deaths
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Can Intranasal Nalmefene Reduce the Number of Opioid Overdose Deaths? Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-30 Edward M. Sellers, Myroslava K. Romach
This Journal recently published a paper describing the pharmacokinetics of a recently Food and Drug Administration (FDA) approved device for intranasal administration of the opioid receptor antagonist nalmefene.1 Parenteral nalmefene was approved in 1995, but was subsequently withdrawn from the market by the manufacturer because of lack of market success. The new formulation (Trade Name Opvee, Indivior
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Pharmacokinetics of Ubrogepant in Healthy Japanese and White Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-23 Ramesh Boinpally, Joel Trugman
Ubrogepant is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. The objectives of this study were to evaluate (1) single-dose pharmacokinetics (PK) and dose proportionality of ubrogepant in Japanese participants, (2) the safety and tolerability of ubrogepant in healthy Japanese and White participants, and (3) to compare
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Cedirogant Population Pharmacokinetics and Pharmacodynamic Analyses of Interleukin-17A Inhibition in Two Phase I Studies in Healthy Participants and Participants with Moderate to Severe Psoriasis Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-17 Corinna S. Maier, Doerthe Eckert, F. Stephen Laroux, Kinjal M. Hew, Ahmed A. Suleiman, Wei Liu, Mohamed-Eslam F. Mohamed
Cedirogant (ABBV-157) is an orally bioavailable inverse agonist of retinoic acid-related orphan receptor gamma thymus. Data from 2 Phase 1 studies were used to characterize cedirogant pharmacokinetics and evaluate target engagement. Cedirogant plasma concentrations and ex vivo interleukin 17A (IL-17A) concentrations from healthy participants and participants with moderate to severe psoriasis (PsO)
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Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-16 Yanrong Wang, Ying Liu, Liyuan Tang, Jie Gao, Hongmin LI, Xinya Dai, Ran Chen, Fengqin Wang
To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268-01). The fasting and fed studies
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Intravenous Ganaxolone: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Healthy Adults Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-17 Maciej Gasior, Aatif Husain, Megan E. Barra, Shruti M. Raja, David MacLeod, Jeffrey T. Guptill, Henrikas Vaitkevicius, Eva Rybak
Ganaxolone, a neuroactive steroid anticonvulsant that modulates both synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA) receptors, is in development for treatment of status epilepticus (SE) and rare epileptic disorders, and has been approved in the United States for treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder in patients ≥2 years old. This phase
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No Influence of Asundexian on Cardiac Repolarization Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-15 Christine Brase, Friederike Kanefendt, Stephanie Loewen, Herbert Himmel, Sebastian Schmitz
Inhibition of activated factor XI reduces thrombogenesis while maintaining physiological hemostasis, with the expectation of reduced bleeding risk compared with standard of care in the clinical setting. Asundexian (BAY 2433334), an activated factor XI inhibitor, is in clinical development for the prevention of thromboembolic events. The effect of asundexian and its plasma metabolite M10 on cardiac
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A Bioequivalence Comparison Between the Once-Daily Extended-Release Tablet and the Twice-Daily Tablet Formulations of Deutetrabenazine at Steady State Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-12 Eva-Maria Sunzel, Laura Rabinovich-Guilatt, Malini Iyengar, Debra Ruffo, Nagnath G. Birajdar, Pippa Loupe, Maria Gutierrez, Mark Forrest Gordon, Giulia Ghibellini
Deutetrabenazine is approved for the treatment of tardive dyskinesia and chorea associated with Huntington's disease. This study compared the exposure between the once-daily (test) and twice-daily (reference) formulations of deutetrabenazine under fed conditions. Using a randomized crossover design, healthy adults (n = 262) received the 24 mg of the test formulation once daily and 12 mg of the reference
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Evaluation of Acarbose Bioequivalence in Healthy Chinese Populations Using Novel Pharmacodynamic End Points Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-10 Linling Que, Zhenzhong Qian, Xuemei Xiang, Ying Ding, Kai Huang, Yichuan Bai, Huanan Zhao, Qing He
Acarbose is a widely used α-glucosidase inhibitor for the management of postprandial hyperglycemia in patients with type 2 diabetes mellitus. Recent pilot studies on acarbose bioequivalence (BE) have successfully identified additional pharmacodynamic (PD) parameters as valid end points. Nevertheless, there was a scarcity of published pivotal studies using novel PD parameters. The purpose of the study
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Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10-Day Dual Therapy Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-10 Kunfeng Yan, Xiaorong Dai, Zhenxing Li, Weiwei Rong, Lei Chen, Xinxin Diao
Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and
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Mass Balance and Metabolite Profile after Single and Multiple Oral Doses of Pritelivir in Healthy Subjects Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-08 Susanne Bonsmann, David McCormick, Jörg Pausch, Michiel de Vries, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Dirk Kropeit
Pritelivir is a helicase-primase inhibitor active against HSV. Two human mass balance trials (a multiple-dose trial and a single-dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C-pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half-life of
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Comparability of Elezanumab Safety, Tolerability, and Pharmacokinetics in Healthy Japanese, Chinese, and White Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-08 Hari V. Kalluri, Matthew R. Rosebraugh, Nils Boehm, Charles Locke, Adam Ziemann, Hao Xiong
Elezanumab is a fully human monoclonal antibody, which is directed against repulsive guidance molecule A. The safety, tolerability, pharmacokinetics (PK), and immunogenicity of elezanumab were assessed in 2 Phase 1 clinical studies. The objective of this study was to assess the PK, safety, tolerability, and immunogenicity following intravenous infusion of elezanumab in healthy adult Japanese, Han Chinese
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Bioequivalence and Safety Assessment of 2 Formulations of Low-Dose Metformin Hydrochloride under Fasting Conditions in Healthy Chinese Participants: A Randomized Phase 1 Clinical Trial Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-08 Ming-Li Sun, Xin-Wen Xu, Chen Liu, Yuan-Xu Tong, Ya-Li Wei, Hui-Juan Liu, Wei Zhang, Xing-He Wang
The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label
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Population Pharmacokinetics of the Novel Adenosine A2A Antagonist/Inverse Agonist KW-6356 and Its Active Metabolite Following Single and Multiple Oral Administration in Healthy Individuals and Patients with Parkinson's Disease Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-04 Tomonori Tayama, Hiroki Okada, Kotoko Ogawa, Douglas Marsteller, Hiroshi Maeda, Matthew W. Hruska, Yoshiyuki Kagawa
KW-6356 is a selective antagonist and inverse agonist of the adenosine A2A receptor. The primary aim of the present analysis was to characterize the pharmacokinetics (PK) of KW-6356 and its active metabolite M6 in healthy subjects and patients with Parkinson's disease (PD). We pooled concentration-time data from healthy subjects and patients with PD who were administered KW-6356. Using these data,
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A Drug-Drug Interaction Study to Evaluate the Impact of Rimegepant on OCT2- and MATE1-Mediated Transport of Metformin in Healthy Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-04 Rajinder Bhardwaj, Beth Morris, Kyle Matschke, Richard Bertz, Robert Croop, Jing Liu
Rimegepant is a calcitonin gene-related peptide receptor antagonist approved for migraine treatment. This phase 1, open-label, single-center, fixed-sequence study evaluated the effect of rimegepant on the pharmacokinetics (PK) of metformin. Twenty-eight healthy participants received metformin 500 mg twice daily from Days 1 to 4 and Days 7 to 10, and once daily on Days 5 and 11. Rimegepant, 75 mg tablet
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Reduced Plasma Levodopa Fluctuations with More Frequent Administration of a Novel Carbidopa/Levodopa Functionally Scored Tablet Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-04 Thomas N. Chase, Ahmad AL-Sabbagh, Minako Koga, Kathleen Clarence-Smith
Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1 study used a new immediate-release (IR) formulation of carbidopa/levodopa 25/100 mg that is functionally scored for easy and precise splitting to evaluate the effects on levodopa plasma variability when smaller doses are taken more frequently
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Pharmacokinetics, Safety, and Tolerability of a Single 5-Day Treatment of Tirbanibulin Ointment 1% in 100 cm2: A Phase 1 Maximal-Use Trial in Patients with Actinic Keratosis Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-07 Janet DuBois, Terry M. Jones, Mark S. Lee, Meritxell Falqués, Vera Kiyasova, Gemma Jiménez, Raquel Otero, Josep-M. Jansat, Jordi Aubets, Rion James Forconi
Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25 cm2. This Phase 1 maximal-use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm2 of the face or balding scalp in adults with actinic keratosis
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Population Pharmacokinetic and Pharmacodynamic Modeling of Romiplostim Biosimilar GP40141 and Reference Product in Healthy Volunteers to Evaluate Biosimilarity Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-03 Igor Makarenko, Aleksandr Petrov, Bella Belova, Valeria Saparova, Anna Arefeva, Kirill Peskov, Nataliya Kudryashova, Alexandr Khokhlov, Roman Drai
GP40141 is a romiplostim biosimilar. A Phase 1 clinical trial was previously conducted in healthy volunteers to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of GP40141 compared to the reference romiplostim (NCT05652595). Using noncompartmental analysis, the biosimilarity of PD end points was determined according to the classical criterion (0.8-1.25). PK end points were also
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Effect of Tacrolimus Formulation (Prolonged-Release vs Immediate-Release) on Its Susceptibility to Drug-Drug Interactions with St. John's Wort Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-04 Katja S. Gümüs, Anna Teegelbekkers, Max Sauter, Andreas D. Meid, Jürgen Burhenne, Johanna Weiss, Antje Blank, Walter E. Haefeli, David Czock
Tacrolimus is metabolized by cytochrome P450 3A (CYP3A) and is susceptible to interactions with the CYP3A and P-glycoprotein inducer St. John's Wort (SJW). CYP3A isozymes are predominantly expressed in the small intestine and liver. Prolonged-release tacrolimus (PR-Tac) is largely absorbed in distal intestinal segments and is less susceptible to CYP3A inhibition. The effect of induction by SJW is unknown
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Utility of Cytochrome P450 4F2 Genotyping to Assess Drug Interaction Risk for Brincidovovir, a Cytochrome P450 4F2 Substrate Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2024-01-03 Tim Tippin, Shamia Faison, Virna Schuck, John Dunn, Odin Naderer
Smallpox was eradicated in 1980 but remains a biothreat due to the potential release of variola virus into the general population. Brincidofovir, the second medicine approved by the US Food and Drug Administration to treat smallpox, is metabolized by oxidative and hydrolytic pathways. The oxidative pathway is initiated by cytochrome P450 4F2 (CYP4F2), an enzyme lacking clinical probes for drug interaction
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Evaluation of Food Effect on the Pharmacokinetics of Velufenacin, a New Muscarinic Receptor Antagonist, in Healthy Subjects Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-29 Juyoung Khwarg, Woo Kyung Chung, Soyoung Lee, Eunsol Yang, Chaelim Ryu, Dae Young Lee, Min Jung Lee, In-Jin Jang, Kyung-Sang Yu, SeungHwan Lee
Velufenacin (DA-8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open-label, single-dose, 4-sequence, 4-treatment, 4-period crossover study was conducted. Subjects received a single oral dose of velufenacin
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Relative Oral Bioavailability and Food Effects of Two Sepiapterin Formulations in Healthy Participants Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-29 Lan Gao, Diksha Kaushik, Yi Xia, Kimberly Ingalls, Sarah Milner, Neil Smith, Ronald Kong
Sepiapterin is an orally administered drug in development for the treatment of phenylketonuria, an inborn error of metabolism characterized by the deficiency of the phenylalanine-metabolizing enzyme phenylalanine hydroxylase. This study characterized the pharmacokinetics, safety, and tolerability of 2 clinical sepiapterin formulations (Phase 1/2, Phase 3) and the effects of food on the pharmacokinetics
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Population Pharmacokinetic Modeling and Simulation of Pudexacianinium (ASP5354) for Dose Setting of a Phase 2 First-in-Patient Study: A Novel Imaging Agent for Intraoperative Ureter Visualization during Abdominopelvic Surgery Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-22 Masako Saito, Tomoki Kojima, Kanji Komatsu, Shin Takusagawa
Pudexacianinium (ASP5354) chloride is an indocyanine green derivative designed to enable enhanced ureter visualization during surgery. The objective of the present analysis was to determine appropriate doses of pudexacianinium for a phase 2, dose-ranging study (NCT04238481). Real-time urine pudexacianinium concentration is considered a good pharmacodynamic surrogate marker, since ureter visualization
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Safety, Tolerability, and Pharmacokinetics of a Novel Oral Phosphodiesterase 4 Inhibitor, ME3183: First-in-Human Phase 1 Study Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-18 Seiji Kato, Naoki Cho, Tomokazu Koresawa, Kazunari Otake, Akiko Kano
A novel, oral phosphodiesterase 4 (PDE4) inhibitor, ME3183, is under development for the treatment of psoriasis, atopic dermatitis, and other inflammatory diseases. To evaluate its safety, tolerability, and pharmacokinetics, double-blind, placebo-controlled, single ascending dose (SAD), and multiple ascending dose (MAD) phase 1 studies were conducted in 126 healthy adults. The food effect was evaluated
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Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-10 Emmanuel O. Fadiran, Edward Hammond, James Tran, Christopher U. Missling, Ene Ette
Pharmacokinetic (PK) data from 28 subjects who received 5-200-mg single ascending doses of ANAVEX3-71, formerly AF710B, were analyzed to characterize the PK of ANAVEX3-71 and its M8 metabolite. PK data from 12 subjects who received 160 mg ANAVEX3-71 under fed and fasted conditions were analyzed to characterize the effect of food on the PK of the drug and its M8 metabolite. PK was characterized using
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A Randomized, Single-Dose, Parallel-Controlled Phase I Clinical Comparison of an Omalizumab Biosimilar Candidate with Reference Omalizumab in Healthy Chinese Male Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-12-06 Jie Cheng, Chenguang Wang, Jin Xu, Chunyang Zhao, Rong Song, Yijun Wang, Yang Zou, Xunmin Zhang, Yong Shan, Jian Zhou, Jing-Ying Jia
This study evaluated the bioequivalence of omalizumab, a humanized monoclonal antibody against immunoglobulin-E (IgE), with one of its biosimilar candidates. The study was designed as a randomized, double-blind, parallel-controlled trial. A total of subjects who met the inclusion criteria and did not meet the exclusion criteria were dynamically randomly assigned to receive the test drug or the reference
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Pharmacological Parameters and Pharmacokinetic Variability Derived from Bioequivalence Trials in a Mexican Population Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-27 Carlos Alejandro Díaz-Tufinio, Vanessa Gonzalez-Covarrubias, José Antonio Palma-Aguirre
Biomedical data from controlled randomized clinical trials (RCTs), from both early pharmacological phase stages and bioequivalence testing, is a valuable resource for obtaining the primary pharmacological characteristics of the studied drugs. Insights on drug safety, and its efficacy to some extent, might be explored as secondary endpoints. The clinical and analytical laboratories for pharmaceutical
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Bioequivalence of 240 mg Apalutamide Tablets and Preparation in Aqueous Food Vehicles for Alternative Administration Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-20 Alex Yu, Mieke Van Uffel, Juhui J. Jiao, Rosamerlinda Rosales, Maura Erba, Nahor Haddish-Berhane
A 240-mg single tablet has been developed with the focus of reducing the pill burden of the apalutamide daily dose of 240 mg (4 × 60-mg tablets). An open-label, randomized, single-dose phase 1 study with a 2-sequence and 2-period crossover design in healthy men determined the bioequivalence of a 240-mg single tablet versus the currently available 4 × 60-mg tablets (Part 1, N = 74) and assessed effect
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Pharmacokinetics and Bioequivalence of Amlodipine Besylate Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-24 Liyuan Tang, Yanrong Wang, Ran Chen, Yuanyuan He, Ying Liu, Na Wang, Xiaoyan Sun, Jingya Song
The purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was
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Bioequivalence Study of Capsules versus Film Tablets Containing Rivaroxaban in Healthy Caucasian Subjects under Fasting and Fed Conditions Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-23 Gökçe Sözer, Ahmet Inal, Zafer Sezer, Wolfgang Martin, Ewald Ottmann, Martin Reinsch, Selma Alime Koru
The bioequivalence (BE) of orally administered capsules versus film tablets containing 20 and 10 mg of rivaroxaban was assessed in 2 single-dose, open-label, randomized 2-way crossover trials with a washout period of at least 1 week. The study for the 10 mg strength was conducted under fasting conditions (n = 68) and the study for the 20 mg strength under fed conditions (n = 52). Blood samples were
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Bioequivalence of 200 mg Amisulpride Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-20 Yi Cao, Jianfen Su
In this study, we compared the pharmacokinetics and safety of a new generic product and a branded reference product of amisulpride tablets. Additionally, we assessed the bioequivalence of the 2 products in healthy Chinese volunteers to acquire sufficient evidence for the marketing approval of the generic drug. Thirty volunteers under fasting and fed conditions were randomly administered a single dose
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Bioequivalence and Pharmacokinetics Study of Two Zidovudine/Lamivudine Tablets in Chinese Healthy Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-20 Xiaomei Huang, Gongzhu Wang, Jian Huang, Wu Liang, Huiyu Guan, Haisha Liu, Yuan Deng, Yu You, Bikui Zhang
Zidovudine/lamivudine tablets are nucleoside reverse transcriptase inhibitors that are used to treat human immunodeficiency virus. The objective of this study was to investigate the bioequivalence and pharmacokinetics (PKs) of test and reference preparations of zidovudine/lamivudine tablets in healthy Chinese subjects. We designed a randomized, open, single-center, single-dose, 2-crossover experiment
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Bioequivalence Study of Epalrestat for Healthy Chinese Subjects Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-16 Dandan Yang, Xiaodan Wang, Yi Duan, Yichao Xu, Zourong Ruan, Bo Jiang, Honggang Lou, Jinliang Chen
Epalrestat is a reversible noncompetitive inhibitor of aldose reductase with selective inhibition of aldose reductase. It can inhibit the accumulation of sorbitol in red blood cells in patients with diabetic peripheral neuropathy and can improve patients’ conscious symptoms and neurological dysfunction. This study was designed to evaluate the bioequivalence in healthy Chinese subjects of a new test
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Effect of the Phosphate Binder Sevelamer Carbonate on the Bioavailability of Enarodustat, an Oral Erythropoiesis Stimulating Agent Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-17 Sudhakar M. Pai, Hiroyuki Yamada
Enarodustat is an orally available hypoxia-inducible factor-prolyl hydroxylase inhibitor which can correct the erythropoietic capacity and improve anemia in chronic kidney disease. Sevelamer carbonate, a non-calcium-based polymeric resin, is one of the commonly prescribed agents for the management of hyperphosphatemia in patients undergoing hemodialysis. This was an open-label, crossover study in healthy
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The Effect of BI 730357 (Retinoic Acid-Related Orphan Receptor Gamma t Antagonist, Bevurogant) on the Pharmacokinetics of a Transporter Probe Cocktail, Including Digoxin, Furosemide, Metformin, and Rosuvastatin: An Open-Label, Non-randomized, 2-Period Fixed-Sequence Trial in Healthy Subjects Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-13 HeeJae Choi, Fenglei Huang, Mary Flack
Evaluating Drug-Drug Interactions (DDIs) for new investigational compounds requires several trials evaluating different drugs with different transporter specificities. By using a cocktail of drugs with different transporter specificities, a single trial could evaluate the pharmacokinetics (PKs) of each cocktail drug simultaneously, reducing the number of clinical DDI trials required for clinical development
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Support for Removing Pharmacodynamic and Clinical Efficacy Testing of Biosimilars: A Critical Analysis Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-14 Sarfaraz K. Niazi
The legislation for biosimilars was introduced in 2010 in the United States as the Biologics Price Competition and Innovation Act (BPCIA) of 2019 for approval under its 351(k) regulation: “REQUIRED INFORMATION. An application submitted under this subsection shall include information demonstrating that” ‘‘(I) the biological product is biosimilar to a reference product based upon data derived from ◦
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Population Pharmacokinetics of Tenofovir Alafenamide Fumarate and Its Metabolite Tenofovir in Healthy Chinese Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-12 Xingfang Ji, Yunfei Li, Zhipeng Wang, Yuan Gao, Ling Wang
Tenofovir alafenamide fumarate (TAF) is a first-line drug for treating hepatitis B virus infection. This study aimed to establish the prodrug–metabolite population pharmacokinetic (PK) model for TAF and its metabolite tenofovir (TFV) in healthy Chinese volunteers and evaluate the factors affecting the PK. Using 1043 TAF and 1198 TFV plasma sample concentrations collected from 67 healthy volunteers
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Population Pharmacokinetic Model of N-Acetylcysteine During Periods of Recurrent Hypoglycemia in Healthy Volunteers Clin. Pharmacol. Drug Dev. (IF 2.0) Pub Date : 2023-11-08 Mohamed S. Fayed, Jillian Brooks, Elizabeth R. Seaquist, Anjali Kumar, Amir Moheet, Lynn Eberly, Usha Mishra, Lisa D. Coles
Recurrent hypoglycemia leads to impaired awareness of hypoglycemia where the blood glucose threshold that elicits the counterregulatory response is lowered. Hypoglycemia-induced oxidative stress is hypothesized to contribute to impaired awareness of hypoglycemia development and hypoglycemia-associated autonomic failure. Our group conducted a randomized, double-blinded, placebo-controlled, crossover