35,658 results match your criteria safety pharmacokinetics


Targeting alterations with adjuvant infigratinib in invasive urothelial carcinoma: the phase III PROOF 302 trial.

Future Oncol 2022 May 24. Epub 2022 May 24.

Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.

PROOF 302 is an ongoing randomized, double-blind, placebo-controlled, adjuvant phase III trial (NCT04197986) in approximately 218 patients from 120 centers worldwide. Eligibility criteria include post-surgical high-risk muscle-invasive upper tract urothelial cancer (85% of patients) or urothelial bladder cancer (15%), susceptible alterations (activating mutations, gene fusions or rearrangements), ≤120 days following radical surgery and ineligible for/or refusing cisplatin-based (neo)adjuvant chemotherapy. Patients receive either oral infigratinib 125 mg or placebo daily on days 1-21 of a 28-day cycle for up to 52 weeks or until recurrence, unacceptable toxicity or death. Read More

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Effect of levetiracetam on nocturnal sleep in patients with epilepsy.

Neurol Neurochir Pol 2022 May 24. Epub 2022 May 24.

Department of Neurology, Medical University, Plovdiv, Bulgaria.

Aim Of The Study: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy.

Clinical Rationale: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Read More

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Biological and Immune Responses to Current Anti-SARS-CoV-2 mRNA Vaccines beyond Anti-Spike Antibody Production.

J Immunol Res 2022 14;2022:4028577. Epub 2022 May 14.

National Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.

Several vaccine strategies are now available to fight the current SARS-CoV-2 pandemic. Those based on the administration of lipid-complexed messenger(m)RNA molecules represent the last frontiers in terms of technology innovation. mRNA molecules coding for the SARS-CoV-2 Spike protein are intramuscularly injected, thereby entering cells by virtue of their encapsulation into synthetic lipid nanovesicles. Read More

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Effects of itraconazole and rifampicin on the pharmacokinetics and safety of youkenafil, a novel phosphodiesterase type 5 inhibitor, in healthy Chinese subjects.

Eur J Pharm Sci 2022 May 20:106213. Epub 2022 May 20.

Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Youkenafil is a novel selective phosphodiesterase type 5 inhibitor to treat erectile dysfunction. In order to study the drug-drug interactions of youkenafil, in vitro experiments were conducted with human liver microsomes and recombinant isoenzymes to identify the effect of cytochrome P450 (CYP) enzymes on the metabolism of youkenafil. Then two clinical studies were performed to investigate the effects of itraconazole and rifampicin (potent CYP3A4/5 inhibitor and inducer, respectively) on the pharmacokinetics of youkenafil and its main metabolite, N-desethyl youkenafil (M1). Read More

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PHARMACOKINETIC-PHARMACODYNAMIC STUDY OF AMPICILLIN-CLOXACILLIN COMBINATION IN INDIAN THOROUGHBRED HORSES (Equus caballus) AND SAFETY EVALUATION OF THE COMPUTED DOSAGE REGIMEN.

J Equine Vet Sci 2022 May 20:104020. Epub 2022 May 20.

In-charge, Remount and Veterinary Corps, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India.

The pharmacokinetics of ampicillin-cloxacillin, given as single intravenously dose of 10 mg.kg (5 mg.kg of ampicillin plus 5 mg. Read More

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Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study.

EBioMedicine 2022 May 20;80:104069. Epub 2022 May 20.

Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.

Background: We conducted an exploratory study to assess the safety tolerability, and anti-fibrotic effects of PRI-724, a CBP/β-catenin inhibitor, in patients with hepatitis C virus (HCV)- and hepatitis B virus (HBV)-induced cirrhosis.

Methods: This multicentre, open-label, non-randomised, non-placebo-controlled phase 1/2a trial was conducted at three hospitals in Japan. Between July 27, 2018, and July 13, 2021, we enrolled patients with HCV- and HBV-induced cirrhosis classified as Child-Pugh (CP) class A or B. Read More

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Systematic Review on Transdermal/Topical Cannabidiol Trials: A Reconsidered Way Forward.

Cannabis Cannabinoid Res 2022 May 23. Epub 2022 May 23.

Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.

This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Read More

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A comprehensive review of intravitreal immunosuppressants and biologicals used in ophthalmology.

Ther Adv Ophthalmol 2022 Jan-Dec;14:25158414221097418. Epub 2022 May 18.

All India Institute of Medical Sciences, New Delhi, New Delhi, India.

Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Read More

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Corrigendum: Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta in Healthy Chinese Male Volunteers.

Front Pharmacol 2022 4;13:907413. Epub 2022 May 4.

Phase I Clinical Trial Laboratory, Affiliated Hospital of Changchun University of Chinese Medicine, Jilin, China.

[This corrects the article DOI: 10.3389/fphar.2021. Read More

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Plasma and breast milk pharmacokinetics of tenofovir alafenamide in mothers with chronic hepatitis B infection.

Aliment Pharmacol Ther 2022 May 22. Epub 2022 May 22.

Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.

Background: Antenatal antiviral therapy (AVT) is effective in preventing mother-to-child transmission in chronic hepatitis B (CHB) and tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There is no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB. Read More

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Combining SJ733, an oral ATP4 inhibitor of Plasmodium falciparum, with the pharmacokinetic enhancer cobicistat: An innovative approach in antimalarial drug development.

EBioMedicine 2022 May 19;80:104065. Epub 2022 May 19.

University of Kentucky College of Pharmacy, Lexington, KY, United States.

Background: SJ733, a newly developed inhibitor of P. falciparum ATP4, has a favorable safety profile and rapid antiparasitic effect but insufficient duration to deliver a single-dose cure of malaria. We investigated the safety, tolerability, and pharmacokinetics of a multidose SJ733 regimen and a single-dose pharmacoboost approach using cobicistat to inhibit CYP3A4, thereby increasing exposure. Read More

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Cabenuva: the last FDA-approved drug to treat HIV.

Expert Rev Anti Infect Ther 2022 May 20. Epub 2022 May 20.

Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.

Introduction: The conventional combination antiretroviral therapy (cART) besides all its benefits, exhibited poor adherence to daily pill administration, life-long treatment period and emergence of viral resistance. The development of long-acting (LA) drugs have changed the management of common medical conditions for human immunodeficiency virus (HIV). Cabenuva is the first LA antiretroviral injectable drug composed of nano-formulation of cabotegravir (CAB) and rilpivirine (RPV). Read More

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Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study.

BMC Cancer 2022 May 20;22(1):565. Epub 2022 May 20.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: Anti-programmed cell death receptor-1 (PD-1) monotherapy is the standard treatment for metastatic melanoma in current. Camrelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody whose safety and efficacy have not been reported in advanced Asian melanoma patients.

Methods: This phase I study investigated the safety, activity, and pharmacokinetics of camrelizumab in Chinese patients with advanced melanoma. Read More

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First-in-human study with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5aR1) antagonist, supported by pharmacokinetic predictions from animals to patients.

Basic Clin Pharmacol Toxicol 2022 May 20. Epub 2022 May 20.

Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland.

Aberrantly controlled activation of the complement system contributes to inflammatory diseases. Safety, tolerability, and pharmacokinetics of single-ascending doses of ACT-1014-6470, a novel orally available complement factor 5a receptor 1 antagonist, were assessed in a randomized, double-blind, placebo-controlled Phase 1 study. Six ACT-1014-6470 doses (0. Read More

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Safety and pharmacokinetic profile of pretomanid in healthy Chinese adults: Results of a phase I single dose escalation study.

Pulm Pharmacol Ther 2022 May 18;73-74:102132. Epub 2022 May 18.

Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing, China. Electronic address:

We investigated the safety, tolerability and pharmacokinetic (PK) profile of pretomanid (formerly PA-824) in healthy Chinese volunteers. This was a single-center, double-blind, placebo-controlled, phase I dose escalation study, in which healthy volunteers were consecutively allocated to increasing pretomanid dose groups (50, 100, 200, 400, 600, 800, or 1000 mg) and randomized to receive pretomanid or matching placebo. The primary objective was to evaluate the safety, tolerability and PK profile of pretomanid. Read More

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Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections.

Expert Opin Drug Metab Toxicol 2022 May 20. Epub 2022 May 20.

College of Pharmacy, University of Illinois at Chicago, Chicaco, IL 60612, USA.

Introduction: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms. Read More

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Concerns About Compounded Bioidentical Menopausal Hormone Therapy.

Cancer J 2022 May-Jun 01;28(3):241-245

From the Department of Obstetrics and Gynecology, Midlife, Health University of Virginia Health System, Charlottesville, VA.

Abstract: Following the release of the Women's Health Initiative data, women began to use compounded bioidentical hormone therapy (cBHT) in the misguided belief of greater safety and efficacy than traditional hormone therapy. New guidelines recommend government-approved hormone therapy for symptomatic healthy menopausal women younger than 60 years or within 10 years of menopause at the time of initiation. For women requesting bioidentical hormones, those similar to the hormones present before menopause, there are many government-approved hormone therapies with extensive pharmacokinetic, safety, and efficacy data provided with package inserts delineating efficacy, safety, and potential risks. Read More

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HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects.

BioDrugs 2022 May 20. Epub 2022 May 20.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

Background: Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products). Read More

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Pharmacokinetics, pharmacodynamics, and safety of verinurad with and without allopurinol in healthy Asian, Chinese, and non-Asian participants.

Pharmacol Res Perspect 2022 Jun;10(3):e00929

CVRM Late Clinical, AstraZeneca BioPharmaceuticals Research and Development Gothenburg, Mölndal, Sweden.

Verinurad is a selective inhibitor of uric acid transporter 1 (URAT1). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of verinurad + allopurinol and verinurad monotherapy in healthy participants. Studies 1 (NCT03836599) and 2 (NCT02608710) were randomized Phase 1 studies. Read More

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First phase 1 clinical study of olaparib in pediatric patients with refractory solid tumors.

Cancer 2022 May 20. Epub 2022 May 20.

Medical Innovation Promotion Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Background: The survival of patients with high-risk, refractory, relapsed, or metastatic solid tumors remains dismal. A poly(ADP-ribose) polymerase (PARP) inhibitor could be effective for the treatment of pediatric solid tumors with defective homologous recombination.

Methods: This open-label, multicenter phase 1 clinical trial evaluated the safety, tolerability, and efficacy of olaparib, a PARP inhibitor, in pediatric patients with refractory solid tumors to recommend a dose for Phase 2 trials. Read More

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Tirzepatide - a dual GIP/GLP-1 receptor agonist - a new antidiabetic drug with potential metabolic activity in the treatment of type 2 diabetes.

Endokrynol Pol 2022 May 20. Epub 2022 May 20.

Department of Internal Medicine, Diabetology and Nephrology, FMS in Zabrze, SUM 41-800 Zabrze , Poland.

The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for up to 65% of postprandial insulin secretion. Tirzepatide, developed by Eli Lilly, is a dual GIP/GLP-1 receptor agonist in the form of a synthetic linear peptide; its acylation technology allows it to bind to albumin, thus making it possible to dose the drug once a week. This review summarizes the key characteristics and pharmacokinetics of tirzepatide. Read More

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Antifungal stewardship in solid organ transplantation.

Transpl Infect Dis 2022 May 20. Epub 2022 May 20.

Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: Antifungal stewardship (AFS) has emerged as an important component of quality in managing invasive fungal infections (IFI), and cost-benefit calculations suggest regular training in AFS is well worth the effort.

Methods: This review will discuss the most common IFIs in SOT-recipients, how to diagnose them, and current recommendations for antifungal treatment and prophylaxis before demonstrating key takeaway points of antifungal stewardship in this high-risk population.

Results: Effective AFS starts before a patient is admitted for solid organ transplantation (SOT), through education and regular interactions of the interdisciplinary clinical team involved in patient management, considering local factors such as epidemiological data and knowledge of diagnostic options including local turnaround times. Read More

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Pharmacological Evaluation of Synthetic Dominant-Negative Peptides Derived from the Competence-Stimulating Peptide of .

ACS Pharmacol Transl Sci 2022 May 20;5(5):299-305. Epub 2022 Apr 20.

Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, United States.

The competence regulon of (pneumococcus) is a quorum-sensing circuitry that regulates the ability of this pathogen to acquire antibiotic resistance or perform serotype switching, leading to vaccine-escape serotypes, via horizontal gene transfer, as well as initiate virulence. Induction of the competence regulon is centered on binding of the competence-stimulating peptide (CSP) to its cognate receptor, ComD. We have recently synthesized multiple dominant-negative peptide analogs capable of inhibiting competence induction and virulence in . Read More

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Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar Insulin 70/30 with US-licensed Humulin® 70/30 formulation in healthy subjects: Results from the RHINE-3 (Recombinant Human INsulin Equivalence-3) study.

Diabetes Obes Metab 2022 May 19. Epub 2022 May 19.

Biocon Biologics Ltd., Bengaluru, Karnataka, India.

Aim: To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar insulin 70/30 (Biocon's Insulin-70/30) and Humulin® 70/30 (Humulin-70/30; Eli Lilly and Company, IN).

Materials And Methods: In this phase-1, automated euglycemic glucose clamp study, 78 healthy subjects were randomized (1:1) to receive a single dose of 0.4 IU/kg of Biocon's Insulin-70/30 and Humulin-70/30. Read More

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First-in-Human PET Imaging of Tissue Factor in Patients with Primary and Metastatic Cancers Using F-labeled Active-Site Inhibited Factor VII (F-ASIS): Potential as Companion Diagnostic.

J Nucl Med 2022 May 19. Epub 2022 May 19.

Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark.

Tissue factor (TF) expression in cancers correlates with poor prognosis. Recently, the first TF-targeted therapy was approved by the US Food and Drug Administration for cervical cancer. To unfold the potential of TF-targeted therapies, correct stratification and selection of patients eligible for treatments may become important for optimization of patient outcomes. Read More

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EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study.

Lancet Oncol 2022 May 16. Epub 2022 May 16.

Leicester Cancer Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK. Electronic address:

Background: Treatment options for malignant pleural mesothelioma are scarce. Tazemetostat, a selective oral enhancer of zeste homolog 2 (EZH2) inhibitor, has shown antitumour activity in several haematological cancers and solid tumours. We aimed to evaluate the anti-tumour activity and safety of tazemetostat in patients with measurable relapsed or refractory malignant pleural mesothelioma. Read More

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Long-term open-label phase I/II extension study of intrathecal idursulfase-IT in the treatment of neuronopathic mucopolysaccharidosis II.

Genet Med 2022 May 19. Epub 2022 May 19.

Takeda Development Center Americas, Inc, Lexington, MA; Affinia Therapeutics, Waltham, MA.

Purpose: Intrathecal (IT) idursulfase-IT for the treatment of cognitive impairment is being investigated in pediatric patients with neuronopathic mucopolysaccharidosis II (MPS II) in addition to intravenous idursulfase. In this article, we report the findings for 54 months of idursulfase-IT treatment in an ongoing phase I/II extension trial (NCT01506141).

Methods: A total of 15 male participants with neuronopathic MPS II (aged 3-11 years at enrollment) who were previously treated with intravenous idursulfase entered the extension study. Read More

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Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis.

Ann Pharmacother 2022 May 19:10600280221096713. Epub 2022 May 19.

Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Objective: The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD).

Data Sources: A literature search of MEDLINE (PubMed) was performed for articles from inception through end-March 2022 using the following search terms: atopic dermatitis, abrocitinib, PF-04965842, methotrexate, cyclosporine, dupilumab, ruxolitinib, and JAK-STAT pathway.

Study Selection And Data Extraction: English articles relating to pharmacology, pharmacokinetics, efficacy, and safety of abrocitinib, and other conventional systemic medications for AD, were included. Read More

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Pharmacokinetics of Vaginal vs Buccal Misoprostol for Labor Induction at Term.

Clin Transl Sci 2022 May 19. Epub 2022 May 19.

Indiana University School of Medicine, Indianapolis, IN, USA.

The IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full-term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women ≥ 14 years of age undergoing induction of labor ≥ 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 µg followed by 50 µg doses every 4 hrs. Read More

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Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healthy Chinese Subjects.

Drug Des Devel Ther 2022 9;16:1365-1381. Epub 2022 May 9.

Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Objective: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.

Methods: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Read More

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