A5035112632- Multiple Sclerosis Research Studies
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- Sphingolipid Metabolism and Signaling
- Pharmacogenetics and Drug Metabolism
- Hepatitis C virus research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Fungal Plant Pathogen Control
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- HIV-related health complications and treatments
- Biosimilars and Bioanalytical Methods
- Hepatitis B Virus Studies
- Chronic Lymphocytic Leukemia Research
- Garlic and Onion Studies
- Immune responses and vaccinations
- Drug Solubulity and Delivery Systems
- 14-3-3 protein interactions
- Tuberculosis Research and Epidemiology
- Pharmacological Receptor Mechanisms and Effects
- Inflammasome and immune disorders
- Heparin-Induced Thrombocytopenia and Thrombosis
Mirati Therapeutics (United States)
2024
Pacific Research Institute
2023
Vitalant
2023
University of California, San Francisco
2023
Bristol-Myers Squibb (United States)
2020-2021
Tulane University
2021
Clarity Biosolutions (United Kingdom)
2020
Sanofi (United States)
2020
Biogen (United States)
2011-2016
Amsterdam UMC Location Vrije Universiteit Amsterdam
2014
<h3>Objective:</h3> To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers participants with multiple sclerosis (MS). <h3>Methods:</h3> In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1–100 mg/kg) or placebo were administered via IV infusion subcutaneous injection to 72 volunteers, (MAD; 0.3–100 mg/kg; separated by 14 days) 47 relapsing-remitting secondary progressive MS. Safety...
Abstract The sphingosine‐1‐phosphate 1 receptor (S1P 1R ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells plays a role in the regulation of chronic inflammation lymphocyte egress from peripheral lymphoid organs. Ozanimod an oral selective modulator S1P 5R receptors clinical development for treatment immune‐mediated, inflammatory diseases. This first‐in‐human study characterized safety, pharmacokinetics (PK), pharmacodynamics (PD) ozanimod 88 healthy volunteers...
Ozanimod is approved for the treatment of relapsing forms multiple sclerosis. Absorption, metabolism, and excretion ozanimod were investigated after a single oral dose 1.0 mg [14C]ozanimod hydrochloride to six healthy subjects. In vitro experiments conducted understand metabolic pathways enzymes involved in metabolism its active metabolites. The total mean recovery administered radioactivity was ∼63%, with ∼26% ∼37% recovered from urine feces, respectively. Based on exposure, major...
(E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) 223,000 M-1s-1}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 35), clinical isolates (5 5), and related picornaviruses (8 8) tested with mean 50% effective concentration (EC50)...
Abstract Ozanimod is a novel, selective, oral sphingosine‐1‐phosphate (1 and 5) receptor modulator in development for multiple sclerosis inflammatory bowel disease. This randomized, double‐blind, placebo‐controlled, positive‐controlled, parallel‐group thorough QT study characterized the effects of ozanimod on cardiac repolarization healthy subjects. Eligible subjects were randomized to 1 2 groups: (escalated from 0.25 mg over 14 days) or placebo (for days). A single dose moxifloxacin 400 was...
<h3>Objective</h3> To better understand ozanimod9s mechanism of action (MOA), we conducted exploratory analyses from a phase 1 study to characterize effect on circulating leukocyte subsets in patients with relapsing multiple sclerosis. <h3>Methods</h3> An open-label pharmacodynamic randomized oral ozanimod hydrochloride (HCl) 0.5 (n = 13) or mg/d 11) for ∼12 weeks (including 7-day dose escalation). Circulating were quantified using flow cytometry (days 28, 56, and 85) epigenetic cell...
A single spot urine collection to measure the ratio of 6β‐hydroxycortisol (6β‐OHC) free cortisol (C) has been proposed as a research tool for assessment CYP3A4 induction. However, intraindividual variability in 6β‐OHC/C under basal conditions and induction not prospectively evaluated, findings on correlation between morning 24‐hour urinary ratios have conflicting. In this study, was assessed 15 healthy adult male volunteers before, during, after oral administration rifampin 600 mg once daily...
Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, potent on the pharmacokinetics pharmacodynamics argatroban was evaluated 14 healthy male volunteers an open‐label, crossover study with 5‐day washout between regimens. Argatroban 1 μg/kg/min infused alone for 5 hours (regimen A) again day 6 7‐day oral regimen 500 mg erythromycin four times daily B). Serial...
Aims To characterize the potential effect of daclizumab high‐yield process (DAC HYP), a monoclonal antibody that blocks high‐affinity interleukin‐2 receptors for treatment multiple sclerosis, on activity cytochrome P450 (CYP) enzymes. Methods Twenty patients with sclerosis received an oral cocktail probe substrates CYP1A2 (caffeine 200 mg), CYP2C9 (warfarin 10 mg/vitamin K CYP2C19 (omeprazole 40 CYP2D6 (dextromethorphan 30 mg) and CYP3A (midazolam 5 two sequential occasions: 7 days before...
Abstract Ozanimod (RPC1063) is an oral selective modulator of the sphingosine‐1‐phosphate 1 and 5 receptors under development for treatment relapsing multiple sclerosis inflammatory bowel disease. The effects high‐fat low‐fat meals on pharmacokinetics (PK) a single dose ozanimod were evaluated in 24 healthy volunteers randomized, open‐label crossover trial. Each subject received 1‐mg hydrochloride 3 meal conditions (fasted, high‐fat, low‐fat), each separated by 7 days. Mean plasma...
The aims of this study were to characterize the single-dose pharmacokinetics (PK) major active metabolites ozanimod, CC112273 and CC1084037, evaluate effect gemfibrozil (a strong inhibitor cytochrome P450 [CYP] 2C8), itraconazole CYP3A P-glycoprotein [P-gp]), rifampin inducer CYP3A/P-gp moderate CYP2C8) on PK ozanimod its in healthy subjects. This was a phase 1, randomized, parallel-group, open-label with two parts. In part 40 subjects randomized receive single oral dose 0.46 mg (group A, n...
The aims of this study were to characterize the multiple-dose pharmacokinetics (PK) ozanimod's major active metabolites (CC112273 and CC1084037) evaluate pharmacodynamic PK interactions with pseudoephedrine (PSE). In phase 1, single-center, randomized, double-blind, placebo-controlled study, 56 healthy adult subjects randomized receive either placebo or ozanimod once daily for 30 days (0.23 mg on 1–4, 0.46 5–7, 0.92 8–10, 1.84 11–30). On day 30, a single oral dose PSE 60 was co-administered...
Danoprevir, a potent, selective inhibitor of HCV NS3/4A protease, has short half-life in humans. Therefore, the feasibility controlled release (CR) formulation to allow less frequent dosing was investigated using experimental approaches and physiological modeling examine whether danoprevir is absorbed colon. Danoprevir absorption studied portal-vein-cannulated monkeys surgically modified make intraduodenal, intrajejunal, intracolonic oral administration possible. In monkeys, apparent up 24 h...
Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a-ribavirin treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10 reduction RNA level at week 12) were given an open-label 100 mg ritonavir (100/100 DNVr) every 12...
Aim Daclizumab high yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α‐subunit of interleukin‐2 receptor and being developed for treatment multiple sclerosis (MS). This manuscript characterized pharmacokinetic–pharmacodynamic (PK–PD) relationships daclizumab HYP in subjects with MS. Methods Approximately 1400 7000 PD measurements each three biomarkers [CD25 occupancy, CD56 bright natural killer (NK) cell count, regulatory T (Treg) count] from four clinical trials...
Daclizumab high-yield process (DAC HYP), a humanized immunoglobulin G1 monoclonal antibody specific for the α subunit (CD25) of high-affinity interleukin-2 receptor, has demonstrated efficacy treatment relapsing forms multiple sclerosis in Phase II and III clinical trials.To characterize pharmacokinetics (PK) DAC HYP following repeated administration 150 mg subcutaneous (SC) dose every 4 weeks (q4wk), proposed regimen patients with relapsing-remitting (RRMS).Twenty-six RRMS received SC q4wk...