journal
MENU ▼
Read by QxMD icon Read
search

Clinical Pharmacology in Drug Development

journal
https://www.readbyqxmd.com/read/29024579/impact-of-the-norepinephrine-prodrug-droxidopa-on-the-qtc-interval-in-healthy-individuals
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28967696/single-dose-pharmacokinetic-study-of-diphenhydramine-hcl-in-children-and-adolescents
#6
Cathy K Gelotte, Brenda A Zimmerman, Gary A Thompson
Diphenhydramine pharmacokinetics were characterized following a single oral dose in children aged 2 to 17 years using a weight- and age-based dosing schedule with more tiers than the current age-based dosing schedule recommended by the nonprescription drug monograph. This study was conducted in 42 subjects, aged 2 to 17 years. Doses were based on a weight-age dosing schedule, ranging from 6.25 to 50 mg. An oral dose was administered with water about 2 hours after a light breakfast. Plasma samples were obtained up to 48 hours after dosing and analyzed for diphenhydramine...
October 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28960888/phase-1-randomized-double-blind-placebo-controlled-studies-on-the-safety-tolerability-and-pharmacokinetics-of-naldemedine-in-healthy-volunteers
#7
Kazuya Fukumura, Takaaki Yokota, Yuko Baba, Juan Camilo Arjona Ferreira
Naldemedine (S-297995) is a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation, a common side effect of opioid therapy. We determined the safety, tolerability, and pharmacokinetic profiles of oral naldemedine in healthy volunteers in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the single ascending dose study, subjects received a single dose of naldemedine (0.1-100 mg; n = 42) or placebo (n = 14). In the multiple ascending dose study, subjects received once-daily naldemedine (3-30 mg; n = 27) or placebo (n = 9) for 10 days...
September 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28941196/pharmacokinetics-safety-and-tolerability-of-vortioxetine-following-single-and-multiple-dose-administration-in-healthy-japanese-adults
#8
Kumi Matsuno, Koki Nakamura, Yutaka Aritomi, Akira Nishimura
Three phase 1 randomized single-center studies assessed the pharmacokinetics, safety, and tolerability of vortioxetine after single- and multiple-dose administration in healthy Japanese adults. Study 1 assessed the pharmacokinetics of vortioxetine after administration of single rising doses to men and multiple doses to men and women; study 2 evaluated vortioxetine pharmacokinetics in elderly adults; and study 3 assessed food effects on vortioxetine pharmacokinetics in healthy men. The primary end points included pharmacokinetic parameters of vortioxetine and incidence of adverse events (AEs)...
September 21, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28940840/ly2963016-insulin-glargine-and-insulin-glargine-lantus-produce-comparable-pharmacokinetics-and-pharmacodynamics-at-two-dose-levels
#9
Xin Zhang, Eric Chen Quin Lam, Mary E Seger, David Coutant, Laiyi Chua, Lai Hock Tan, Danny Soon, Helle Linnebjerg
LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products with identical amino acid sequences. This was a phase 1 single-site, randomized, subject- and investigator-blinded, 4-treatment, 4-period crossover study to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LY IGlar and IGlar at 2 different doses. Fasted healthy subjects were randomly assigned to receive 2 single doses of LY IGlar and IGlar (0.3 and 0.6 U/kg for each product). Blood samples were collected up to 24 hours postdose to assess PK, and a euglycemic clamp lasting up to 24 hours postdose was conducted to assess PD...
September 21, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28884969/evaluation-of-bioequivalence-between-the-new-procaterol-hydrochloride-hydrate-dry-powder-inhaler-and-the-approved-dry-powder-inhaler-in-patients-with-asthma-in-a-randomized-double-blind-double-dummy-crossover-comparison-study-a-phase%C3%A2-3-study
#10
Ryo Shirai, Yuki Suzaki, Kyoko Sato, Yuko Takeuchi, Issei Tokimatsu, Nobuyuki Koga, Junichi Kadota, Kyoichi Ohashi
Procaterol hydrochloride hydrate (procaterol) is a β2 -adrenergic receptor agonist that induces a strong bronchodilatory effect. The procaterol dry powder inhaler (DPI) has been frequently used in patients with bronchial asthma or chronic obstructive pulmonary disease. We evaluated the bioequivalence and safety between the new procaterol DPI (new DPI) and the approved procaterol DPI (approved DPI). This study was a randomized, double-blind, double-dummy, crossover comparison to evaluate the pharmacodynamic equivalence of the new DPI and the approved DPI in patients with bronchial asthma...
September 8, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28881493/safety-tolerability-and-pharmacokinetics-of-therapeutic-and-supratherapeutic-doses-of-tramadol-hydrochloride-in-healthy-adults-a-randomized-double-blind-placebo-controlled-multiple-ascending-dose-study
#11
Byron DeLemos, Henry M Richards, Joris Vandenbossche, Jay Ariyawansa, Jaya Natarajan, Binu Alexander, Tage Ramakrishna, Thomas Murtaugh, Hans-Jürgen Stahlberg
This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91...
September 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28881472/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-domagrozumab-pf-06252616-an-antimyostatin-monoclonal-antibody-in-healthy-subjects
#12
Indranil Bhattacharya, Sylvester Pawlak, Shannon Marraffino, Jared Christensen, Sarah P Sherlock, Christine Alvey, Carl Morris, Steven Arkin, Michael Binks
Safety, tolerability, anabolic effects, pharmacokinetics, and pharmacodynamics of single ascending and multiple doses of domagrozumab, an antimyostatin monoclonal antibody, were assessed following intravenous (IV) and subcutaneous (SC) administration in healthy subjects. A range of single ascending dose levels between 1 and 40 mg/kg IV and multiple doses (3 doses) of 10 mg/kg IV were tested (n = 8 per cohort). Additionally, a 3 mg/kg SC (n = 8) cohort also received domagrozumab. Magnetic resonance imaging and whole-body dual-energy x-ray absorptiometry imaging were conducted to investigate the anabolic effects of domagrozumab...
September 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28881418/population-pharmacokinetic-evaluation-and-missed-dose-simulations-for-eslicarbazepine-acetate-monotherapy-in-patients-with-partial-onset-seizures
#13
Soujanya Sunkaraneni, David Blum, Elizabeth Ludwig, Vaishali Chudasama, Jill Fiedler-Kelly, Marketa Marvanova, Jacquelyn Bainbridge, Luann Phillips
Given the potential consequences of antiepileptic therapy nonadherence, missed-dose scenarios of 12- to 48-hour dose delays (4-hour intervals) for eslicarbazepine acetate monotherapy were evaluated using simulated plasma concentrations of a population pharmacokinetic model (representing 493 subjects). When 1600-mg doses were delayed 12 to <16 or 36 to <44 hours, simulations showed immediate administration of 1600 mg followed by the same dose at the scheduled time maintained plasma concentrations within the target concentration range...
September 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28816033/selection-of-12-hour-sustained-release-acetaminophen-paracetamol-formulation-through-comparison-of-pharmacokinetic-profiles-of-4-sustained-release-prototype-formulations-and-standard-acetaminophen-formulation-an-open-label-randomized-proof-of-principle-pharmacokinetic
#14
Yong Yue, Dongzhou J Liu
Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified-release and immediate-release (IR) formulations requiring 3- or 4-times-daily dosing. This phase 1 open-label crossover study compared pharmacokinetic profiles of single 2000-mg doses of 4 different sustained-release (SR) formulations of APAP (designed to allow twice-daily dosing) against two 1000-mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC ) of 4 μg/mL...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28816026/evaluation-of-a-12-hour-sustained-release-acetaminophen-paracetamol-formulation-a-randomized-3-way-crossover-pharmacokinetic-and-safety-study-in-healthy-volunteers
#15
Yong Yue, Agron Collaku, Dongzhou J Liu
Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (TC≥4μg/mL )...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28815997/bioequivalence-and-safety-of-twice-daily-sustained-release-paracetamol-acetaminophen-compared-with-3-and-4-times-daily-paracetamol-a-repeat-dose-crossover-pharmacokinetic-study-in-healthy-volunteers
#16
Dongzhou J Liu, Agron Collaku
Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily)...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28800211/pharmacokinetics-and-bioequivalence-of-branded-and-generic-formulations-of-dofetilide-0-5-mg-capsules-after-single-dose-administration-in-healthy-subjects
#17
James T VanderLugt, Charles Bon, Dean Knuth, Rhonda Schreiber, Michael D Ruff
Class III antiarrhythmics are preferred therapy for managing atrial fibrillation/flutter. Dofetilide 0.5-mg capsules were US Food and Drug Administration (FDA) approved in 1999 to treat atrial fibrillation/flutter. Bioequivalence of generic dofetilide is important for treating arrhythmias because drug concentrations must be consistent to maintain normal sinus rhythm. Generic dofetilide 0.5-mg capsule pharmacokinetics were compared with branded product in 2 open-label, 2-way crossover, single-dose studies - 1 study each in fasted and fed healthy subjects...
August 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28800206/relative-bioavailability-of-fixed-dose-combinations-of-tamsulosin-and-dutasteride-results-from-2-randomized-trials-in-healthy-male-volunteers
#18
Olivia Burns, John Zhu, Michael J Manyak, Ramiya Ravindranath, Fariba Koosha, Nazneen Haque, Sally Chung
The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed-dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5-mg capsule [Avodart(®) ] + 1 tamsulosin hydrochloride 0.2-mg orally disintegrating tablet [Harnal D(®) ]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open-label, randomized, single-dose, crossover studies in healthy male adults aged 18-65 years...
August 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28783872/evaluation-of-potential-drug-drug-interaction-between-delayed-release-dimethyl-fumarate-and-a-commonly-used-oral-contraceptive-norgestimate-ethinyl-estradiol-in-healthy-women
#19
Bing Zhu, Ivan Nestorov, Guolin Zhao, Venkata Meka, Mark Leahy, Jeanelle Kam, Sarah I Sheikh
Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed)...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28783871/cardiac-safety-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator-results-of-a-thorough-qt-qtc-study
#20
Jonathan Q Tran, Jeffrey P Hartung, Allan D Olson, Boaz Mendzelevski, Gregg A Timony, Marcus F Boehm, Robert J Peach, Sheila Gujrathi, Paul A Frohna
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17...
August 7, 2017: Clinical Pharmacology in Drug Development
journal
journal
43835
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"