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Clinical Pharmacology in Drug Development

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https://www.readbyqxmd.com/read/29228473/population-pharmacokinetics-of-desvenlafaxine-pharmacokinetics-in-korean-versus-us-populations
#1
Alice I Nichols, Sam Liao, Richat Abbas
Desvenlafaxine exposure in Korean and US populations was compared using population pharmacokinetic (PK) analysis. Data from a single- and multiple-dose study of desvenlafaxine (50, 100, and 200 mg) in 30 healthy Korean subjects were added to a population PK model previously developed using sparse PK samples from patients with major depressive disorder, including 140 Korean patients, combined with rich PK data from healthy volunteers. The structural PK model was an open 1-compartment linear disposition model with parallel first-order and 0-order inputs...
December 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29197175/pharmacokinetics-of-diclofenac-and-hydroxypropyl-%C3%AE-cyclodextrin-hp%C3%AE-cd-following-administration-of-injectable-hp%C3%AE-cd-diclofenac-in-subjects-with-mild-to-moderate-renal-insufficiency-or-mild-hepatic-impairment
#2
Douglas A Hamilton, Cynthia C Ernst, William G Kramer, Donna Madden, Eric Lang, Edward Liao, Peter G Lacouture, Atulkumar Ramaiya, Daniel B Carr
Given their established analgesic properties, nonsteroidal anti-inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl-β-cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD-diclofenac; and (2) the PK of HPβCD following administration of HPβCD-diclofenac and intravenous itraconazole formulated with HPβCD in healthy adults...
December 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29197167/to-take-or-not-to-take-with-meals-unraveling-issues-related-to-food-effects-labeling-for-oral-antineoplastic-drugs
#3
Jiexin Deng, Satjit S Brar, Lawrence J Lesko
There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models...
December 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29193747/single-dose-bioequivalence-of-two-mini-nicotine-lozenge-formulations
#4
Scott C Rasmussen, William D Becker, Gilbert M Shanga
Diverse nicotine replacement therapy options may improve consumer usage. This study was conducted to establish the bioequivalence of a new cherry-flavored mini lozenge with that of a currently marketed mint-flavored mini lozenge. The rate (Cmax ) and extent (AUC0-t ) of plasma nicotine absorption were compared after administration of 2- and 4-mg doses of each lozenge in healthy adult smokers (n = 43). The bioequivalence of each respective dose was established based on the 90% confidence interval for the ratio of geometric means for both Cmax and AUC0-t lying within the range of 0...
November 28, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29136343/pharmacokinetics-pharmacodynamics-and-safety-of-a-long-acting-human-growth-hormone-mod-4023-in-healthy-japanese-and-caucasian-adults
#5
William G Kramer, Michal Jaron-Mendelson, Ronit Koren, Oren Hershkovitz, Gili Hart
Daily injections of growth hormone (GH) as replacement therapy in GH-deficient (GHD) patients may cause poor compliance and inconvenience. C-terminal peptide-modified human GH (MOD-4023) has been developed for once-weekly administration in GHD adults and children. In the present study, the pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous dose of MOD-4023 were evaluated in healthy Caucasian and Japanese adults, using a phase 1 double-blind, vehicle-controlled, randomized study design...
November 14, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125719/safety-pharmacokinetics-and-immunogenicity-of-obiltoxaximab-after-intramuscular-administration-to-healthy-humans
#6
Christa F Nagy, Timothy S Leach, Alex King, Robert Guttendorf
Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125718/effects-of-high-and-low-fat-meals-on-the-pharmacokinetics-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator
#7
Jonathan Q Tran, Jeffrey P Hartung, Cindy-Ann Tompkins, Paul A Frohna
Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease. The effects of high-fat and low-fat meals on the pharmacokinetics (PK) of a single oral dose of ozanimod were evaluated in 24 healthy volunteers in a randomized, open-label crossover trial. Each subject received a 1-mg dose of ozanimod hydrochloride under 3 meal conditions (fasted, high-fat, and low-fat), each separated by 7 days...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125715/two-phase-1-open-label-single-dose-randomized-crossover-studies-to-assess-the-pharmacokinetics-safety-and-tolerability-of-orally-administered-granules-of-secnidazole-2-g-in-healthy-female-volunteers-under-different-administration-conditions
#8
Helen S Pentikis, Nikki Adetoro
Bacterial vaginosis (BV) is the most common vaginal infection in reproductive-age women and a significant risk factor for sexually transmitted diseases and pregnancy complications. Standard 5- to 7-day antimicrobial treatments for BV are associated with high rates of recurrence and adverse events. SYM-1219 is a novel granule formulation containing 2 g of secnidazole, developed as an oral, single-dose BV treatment. Two phase 1, open-label, single-center, randomized, crossover trials (studies 102 and 103) assessed the pharmacokinetics and safety of SYM-1219 single doses (≥7-day washout between doses) in healthy, nonpregnant women aged 18 to 65 years inclusive...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125703/pharmacokinetics-and-safety-of-mavatrep-jnj-39439335-a-trpv1-antagonist-in-healthy-japanese-and-caucasian-men-a-double-blind-randomized-placebo-controlled-sequential-group-phase-1-study
#9
Prasarn Manitpisitkul, Kevin Shalayda, Lucille Russell, Panna Sanga, Bhavna Solanki, Joseph Caruso, Yuki Iwaki, John A Moyer
This single-center, double-blind, placebo-controlled, sequential-group phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of mavatrep (JNJ-39439335), a transient receptor potential vanilloid 1 antagonist, in healthy Japanese and caucasian subjects. In part 1, a single-ascending-dose study, 50 subjects (25 each healthy Japanese and caucasians) were enrolled and received a single oral dose of 10, 25, or 50 mg mavatrep. Caucasian subjects were matched to Japanese subjects with respect to age (±5 years) and body mass index (±5 kg/m2 )...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125702/single-dose-pharmacokinetics-of-oral-cannabidiol-following-administration-of-ptl101-a-new-formulation-based-on-gelatin-matrix-pellets-technology
#10
Jacob Atsmon, Daphna Heffetz, Lisa Deutsch, Frederic Deutsch, Hagit Sacks
Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125700/bioavailability-and-pharmacokinetics-of-trpv1-antagonist-mavatrep-jnj-39439335-tablet-and-capsule-formulations-in-healthy-men-two-open-label-crossover-single-dose-phase-1-studies
#11
Prasarn Manitpisitkul, Kevin Shalayda, Lucille Russell, Panna Sanga, Yinka Williams, Bhavna Solanki, Joseph Caruso, John A Moyer
To improve room temperature stability and oral bioavailability of mavatrep (JNJ-39439335, a transient receptor potential vanilloid subtype-1 antagonist), various formulations were initially developed and evaluated in 2 phase 1 open-label, randomized, 3-way crossover studies in healthy participants. Study 1 evaluated 2 new overencapsulated tablet formulations (formulations B and C) relative to an overencapsulated early tablet formulation (formulation A), using mavatrep HCl salt form. Because these tablets were still not room-temperature stable, in study 2: two free-base solid dispersion amorphous formulations (formulations D and E) were evaluated relative to the best encapsulated formulation from study 1 (formulation C) and also food effect...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29112329/in-vitro-and-in-vivo-investigation-of-potential-for-complex-cyp3a-interaction-for-pf-00251802-dagrocorat-a-novel-dissociated-agonist-of-the-glucocorticoid-receptor
#12
Sharon L Ripp, Arnab Mukherjee, Heather Eng, Thomas Stock, Dona Fleishaker, Tina Checchio, Brinda Tammara
The dissociated agonists of the glucocorticoid receptor are a novel class of agents in clinical development for rheumatoid arthritis. PF-04171327 (fosdagrocorat) is a phosphate ester prodrug of PF-00251802 (dagrocorat), a selective high-affinity partial agonist of the glucocorticoid receptor, which is further metabolized to PF-04015475. This study evaluated the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of PF-00251802 and PF-04015475 in vitro and used model-based prediction approaches to estimate clinical impact...
November 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29058821/a-thorough-qt-study-to-evaluate-the-effects-of-supratherapeutic-doses-of-ledipasvir-on-the-qtc-interval-in-healthy-subjects
#13
Polina German, Anita Mathias, Diana M Brainard, Qinghua Song, John Ling, Brian P Kearney
This study evaluated the effect of supratherapeutic exposure of the anti-HCV drug ledipasvir on the QTc interval in healthy subjects. Sixty healthy volunteers were randomized to receive twice-daily blinded ledipasvir (120 mg) or placebo, administered for 10 days each, or single doses of open-label moxifloxacin (400 mg). Serial plasma samples for ledipasvir concentration analysis were collected after each treatment. Triplicate time-matched electrocardiograms were collected at baseline and after each treatment...
October 23, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29058816/absolute-bioavailability-of-bosutinib-in-healthy-subjects-from-an-open-label-randomized-2-period-crossover-study
#14
Poe-Hirr Hsyu, Daniela Soriano Pignataro, Kyle Matschke
This study evaluated the absolute bioavailability of bosutinib and assessed its safety and tolerability after single-dose oral and intravenous administration. In this phase 1 open-label, 2-sequence, 2-period crossover study, healthy, fed subjects aged 18-55 years were randomized to 1 of 2 treatment sequences (n = 7/sequence): oral bosutinib (100 mg × 5) followed by intravenous bosutinib (120 mg in approximately 240 mL over 1 hour), with a ≥14-day washout, or intravenous bosutinib and then oral bosutinib...
October 23, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29058801/pharmacokinetics-of-the-bcl-2-inhibitor-venetoclax-in-healthy-chinese-subjects
#15
Tommy T Cheung, Ahmed Hamed Salem, Rajeev M Menon, Wijith P Munasinghe, Orlando F Bueno, Suresh K Agarwal
Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first-generation Han Chinese subjects received a single 100-mg dose of venetoclax following a low-fat breakfast...
October 23, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29024579/impact-of-the-norepinephrine-prodrug-droxidopa-on-the-qtc-interval-in-healthy-individuals
#16
William B White, L Arthur Hewitt, Ali A Mehdirad
A double-blind, 4-period crossover study (NCT01327066) was conducted to assess the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in healthy subjects. Subjects were randomized to receive a single dose of droxidopa 600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the positive control, moxifloxacin 400 mg, and placebo, each separated by a 3-day washout period. Patients were monitored by continuous Holter monitoring, and electrocardiograms (ECGs) were extracted 0...
October 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29024542/the-relative-bioavailability-food-effect-and-drug-interaction-with-omeprazole-of-momelotinib-tablet-formulation-in-healthy-subjects
#17
Yan Xin, Lixin Shao, Julie Maltzman, Dimitrios Stefanidis, Jeffrey Hemenway, Thomas Tarnowski, Wei Deng, Jeffrey A Silverman
Momelotinib is a potent and selective small-molecule inhibitor of JAK1/2 that is under investigation for the treatment of myeloproliferative neoplasms. In a phase 1/2 study in myelofibrosis patients, once-daily dosing of a 300-mg momelotinib capsule was selected for further development based on a favorable benefit:risk profile. A tablet formulation was recently developed for further clinical evaluation. In this study, the relative bioavailability of the tablet formulation versus the initial capsule formulation and the effect of food and omeprazole on the pharmacokinetics of a single-dose momelotinib tablet were evaluated in healthy subjects...
October 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29024490/categorization-of-abuse-potential-related-adverse-events
#18
Edward M Sellers, Myroslava K Romach
All drugs with central nervous system activity must undergo an assessment of their abuse potential, and these data must be included in a New Drug Application. Part of this assessment is an analysis of treatment-emergent adverse events that occur during clinical development. Using an iterative consensus strategy, we evaluated and grouped an available list of 213 flag terms for abuse potential from the Food and Drug Administration, into categories and assessed the relevance of the terms to primary abuse behavior...
October 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28967708/assessment-of-safety-tolerability-pharmacokinetics-and-pharmacological-effect-of-orally-administered-cort125134-an-adaptive-double-blind-randomized-placebo-controlled-phase-1-clinical-study
#19
Hazel Hunt, Kirsteen Donaldson, Mark Strem, Vanessa Zann, Pui Leung, Suzanne Sweet, Alyson Connor, Dan Combs, Joseph Belanoff
CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts...
October 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28967706/pharmacokinetics-and-safety-of-letermovir-coadministered-with-cyclosporine-a-or-tacrolimus-in-healthy-subjects
#20
Dirk Kropeit, Oliver von Richter, Hans-Peter Stobernack, Helga Rübsamen-Schaeff, Holger Zimmermann
Letermovir is being developed for human cytomegalovirus infection treatment and prophylaxis. In patients receiving transplants, antivirals are coadministered with cyclosporine A (CsA) or tacrolimus (TAC) immunosuppressants. Therefore, we investigated the potential for letermovir-immunosuppressant interactions. In 2 phase 1 clinical trials either CsA 50 mg or TAC 5 mg was administered to healthy males. Following washout, letermovir 80 mg was dosed twice daily for 7 and 11 days in the CsA and TAC trials, respectively, with a second dose of immunosuppressant coadministered with letermovir at steady state...
October 2, 2017: Clinical Pharmacology in Drug Development
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