Abstract：
:Upadacitinib is a selective Janus kinase 1 inhibitor that was recently approved for treatment of rheumatoid arthritis and is currently being evaluated for treatment of several other autoimmune diseases, including atopic dermatitis (AD). The relationships between upadacitinib plasma exposure and efficacy (assessed as Eczema Area Severity Index [EASI]-75, EASI-90, and Investigator Global Assessment [IGA] 0/1) in subjects with moderate to severe atopic dermatitis were characterized using the data from 167 subjects who were enrolled in a phase 2b dose-ranging study. Subjects were randomized to receive once daily doses of monotherapy treatment with upadacitinib extended-release 7.5, 15, or 30 mg or placebo for 16 weeks. Logistic regression models were developed and utilized to simulate efficacy for upadacitinib with an approximate phase 3 sample size. Based on exposure-response models, 15 mg once daily is predicted to achieve EASI-75, EASI-90, and IGA 0/1 responses in 48%, 26%, and 29% of subjects, respectively, compared with placebo responses of 9%, 2%, and 2%, respectively, whereas 30 mg once daily is predicted to provide an additional approximately 20% greater efficacy for these end points relative to 15 mg once daily. These analyses supported the selection of upadacitinib doses that are being evaluated in ongoing global phase 3 studies in atopic dermatitis.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Mohamed MF,Gopalakrishnan S,Teixeira HD,Othman AAdoi
10.1002/jcph.1782subject
Has Abstractpub_date
2020-11-06 00:00:00eissn
0091-2700issn
1552-4604pub_type
杂志文章abstract：:The relationship between indenolol (an investigational agent) plasma levels and the drug's effect on blood pressure and heart rate was investigated after single and repeated once daily administration at two dosage levels (60 mg and 120 mg) in two different groups of patients with first or second stage hypertension, ac...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1985.tb02851.x
更新日期：1985-07-01 00:00:00
abstract：:The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02694.x
更新日期：1982-08-01 00:00:00
abstract：:A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post d...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1998.38.s1.55
更新日期：1998-12-01 00:00:00
abstract：:The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of c...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1997.tb04263.x
更新日期：1997-10-01 00:00:00
abstract：:Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1992.tb03798.x
更新日期：1992-11-01 00:00:00
abstract：:Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. T...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/00912700022008793
更新日期：2000-02-01 00:00:00
abstract：:Nateglinide (Starlix, SDZ DJN 608 or A-4166), a new insulinotropic agent, is intended to be administered prior to a meal in order to improve early insulin release in non-insulin-dependent diabetes mellitus patients. The effects of a meal on the oral bioavailability and pharmacodynamic actions of nateglinide were inves...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912709922007606
更新日期：1999-02-01 00:00:00
abstract：:Aliskiren is the first in a new class of orally active, direct renin inhibitors for the treatment of hypertension. This open-label, nonrandomized, single-center, parallel-group study compared the pharmacokinetics and safety of a single 300-mg oral dose of aliskiren in patients with mild, moderate, or severe hepatic im...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270006294404
更新日期：2007-02-01 00:00:00
abstract：:We compared the pharmacokinetic (PK) exposure parameters of efavirenz (EFV) and its major inactive metabolite, 8-hydroxy-efavirenz (8-OH-EFV), in an open-label, single-sequence, and parallel design of HIV-infected and tuberculosis (TB)-HIV-coinfected Ethiopian patients in the HIV-TB Pharmagene study with 20 and 33 pat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1002/jcph.756
更新日期：2016-12-01 00:00:00
abstract：:Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerativ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270007301623
更新日期：2007-08-01 00:00:00
abstract：:The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German drug regulation authority, issued guidelines for determining whether bioavailability/bioequivalence studies are required for certain drugs. This decision tree is based on pharmacodynamic, pharmacokinetic, and physicochemical criteria. Details ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1998.tb04385.x
更新日期：1998-10-01 00:00:00
abstract：:Pain is considered the most common complaint worldwide for which patients seek treatment. Conventional analgesic agents play an important role in modern pain therapy, but they cause several adverse effects. Therefore, newer and better analgesics continue to be investigated. In this controlled clinical trial, the autho...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004267809
更新日期：2004-11-01 00:00:00
abstract：:A two-period, crossover trial was conducted in the hypobaric chamber on human subjects to compare the influence of inflight exercise (experimental) and restricted activity (control) on altitude decompression sickness (DCS) during simulated extravehicular activities. Out of 39 pairs (total of 78 exposures), 4 cases of ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1994.tb02012.x
更新日期：1994-06-01 00:00:00
abstract：:In a double-blind, placebo-controlled study, an attempt was made to evaluate butaclamol in chronic schizophrenic patients using chlorpromazine (CPZ) as the standard comparative drug. With doses up to 50 mg/day, butaclamol was shown to have significant antipsychotic activity comparable to CPZ but with a much higher inc...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1977.tb05646.x
更新日期：1977-08-01 00:00:00
abstract：:Buprenorphine administered sublingually is a promising treatment for opiate dependence. Utilizing a new, sensitive, and specific gas chromatographic electron-capture detector assay, the absolute bioavailability of sublingual buprenorphine was determined in six healthy volunteers by comparing plasma concentrations afte...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/009127009703700106
更新日期：1997-01-01 00:00:00
abstract：:Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentr...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.205
更新日期：2014-02-01 00:00:00
abstract：:ReN1869 (NNC 05-1869) is a novel, selective H1 receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied. The study was a randomized, double-blind, placebo-...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270002239708
更新日期：2003-01-01 00:00:00
abstract：:Levonantradol and its desacetylated metabolite (desacetyllevonantradol) produced a dose-dependent increase in the hot plate and tail flick response latencies following intrathecal administration in a dose range from 4 to 40 micrograms. No difference in potency between the two drugs was observed, as defined by the ED50...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb02612.x
更新日期：1981-08-01 00:00:00
abstract：:Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb03076.x
更新日期：1987-08-01 00:00:00
abstract：:Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg dai...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011423664
更新日期：2012-11-01 00:00:00
abstract：:Moxifloxacin is used in thorough QT studies to assess sensitivity for detection of an increase in QTc. Moxifloxacin is usually over-encapsulated for blinding. However, there is concern that over-encapsulation alters its pharmacokinetics. In a 4-arm, randomized crossover study, 22 volunteers received over-encapsulated ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009356298
更新日期：2010-11-01 00:00:00
abstract：:To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-do...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007309705
更新日期：2008-02-01 00:00:00
abstract：:Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and cont...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270006292163
更新日期：2006-11-01 00:00:00
abstract：:The chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 , a key mediator in inflammatory disorders. In this randomized, double-blind, placebo-controlled study we investigated the single- and multiple-dose tolerability, pharmacokinetics...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.478
更新日期：2015-07-01 00:00:00
abstract：:A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favo...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1975.tb02382.x
更新日期：1975-08-01 00:00:00
abstract：:The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were a...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1002/j.1552-4604.1994.tb01985.x
更新日期：1994-11-01 00:00:00
abstract：:The aim of this pharmacokinetic analysis was to develop and validate a population pharmacokinetic model for R- and S-ibuprofen from samples obtained after 3 successive administrations of ibuprofen (10-5-5 mg/kg) at 24-hour intervals to preterm newborn infants aged from <6 hours to 8 days of life. A model including uni...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270008323752
更新日期：2008-12-01 00:00:00
abstract：:The intravenous infusion of cetiedil to a group of ten male volunteers elicited atropine-like side effects on salivation, bronchomotor tone and visual accommodation. With repeated infusions of cetiedil, the incidence as well as the duration of the side effects were reduced significantly, indicating the development of ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02668.x
更新日期：1982-05-01 00:00:00
abstract：:MC4-NN2-0453 is a novel, long-acting, selective, melanocortin-4-receptor agonist developed for treatment of obesity. This first-human-dose, randomized, double-blind, placebo-controlled trial investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of MC4-NN2-0453 in ov...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.211
更新日期：2014-04-01 00:00:00
abstract：:The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five su...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1991.tb01887.x
更新日期：1991-01-01 00:00:00
