AI Article Synopsis
- This study focused on understanding the pharmacokinetics (how the drug is processed in the body) of ozanimod's active metabolites and how it interacts with pseudoephedrine (PSE).
- Conducted as a phase 1 trial, 56 healthy volunteers received varying doses of ozanimod for 30 days, followed by a single dose of PSE to assess blood pressure changes and drug interactions.
- Results showed that ozanimod and its metabolites significantly contributed to drug exposure, but their combined use with PSE did not affect blood pressure or PSE's pharmacokinetics, indicating they were well-tolerated together.
Article Abstract
Introduction: The aims of this study were to characterize the multiple-dose pharmacokinetics (PK) of ozanimod's major active metabolites (CC112273 and CC1084037) and to evaluate the pharmacodynamic and PK interactions with pseudoephedrine (PSE).
Methods: In this phase 1, single-center, randomized, double-blind, placebo-controlled study, 56 healthy adult subjects were randomized to receive either placebo or ozanimod once daily for 30 days (0.23 mg on days 1-4, 0.46 mg on days 5-7, 0.92 mg on days 8-10, and 1.84 mg on days 11-30). On day 30, a single oral dose of PSE 60 mg was co-administered with placebo or ozanimod. Maximum time-matched change in systolic blood pressure (SBP) from baseline (day 29) following PSE administration on day 30 was calculated. Plasma PK parameters for ozanimod, CC112273, CC1084037, and PSE were estimated using noncompartmental methods.
Results: Fifty-two subjects (92.9%) completed the study. Following multiple dosing, approximately 94% of circulating total active drug exposure was represented by ozanimod (6%), CC112273 (73%), and CC1084037 (15%). Exposures of CC112273 and CC1084037 were highly correlated. Mean maximum time-matched change from baseline for SBP was not significantly different between ozanimod + PSE and placebo + PSE. Ozanimod also had no effect on the PK of PSE. Co-administration of ozanimod with a single dose of PSE in healthy subjects was generally well tolerated. While CC112273 and CC1084037 selectively inhibited monoamine oxidase (MAO)-B in vitro, both active metabolites do not inhibit platelet MAO-B activity in vivo.
Conclusion: Concomitant administration of ozanimod with PSE, a sympathomimetic agent, did not potentiate the effects on blood pressure.
Trial Registration: NCT03644576.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595987 | PMC |
| http://dx.doi.org/10.1007/s12325-020-01500-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In vitro assessment of the binding and functional responses of ozanimod and its plasma metabolites across human sphingosine 1-phosphate receptors.
Eur J Pharmacol
February 2023
Bristol Myers Squibb, Princeton, NJ, USA. Electronic address:
Ozanimod is approved in multiple countries for the treatment of adults with either relapsing multiple sclerosis or moderately to severely active ulcerative colitis. Ozanimod is metabolized in humans to form seven active plasma metabolites, including two major active metabolites CC112273 and CC1084037, and an inactive metabolite. Here, the binding and activity of ozanimod and its metabolites across human sphingosine 1-phosphate receptors were determined.
View Article and Find Full Text PDFAbsorption, Metabolism, and Excretion, In Vitro Pharmacology, and Clinical Pharmacokinetics of Ozanimod, a Novel Sphingosine 1-Phosphate Receptor Modulator.
Drug Metab Dispos
May 2021
Non-clinical Research and Development, Bristol Myers Squibb, Summit, New Jersey (S.S., U.Y., D.D., X.W., G.K.); Drug Metabolism and Pharmacokinetics, Escient Pharmaceuticals, San Diego, California (J.B.); Neuroscience TRC, Bristol Myers Squibb, Princeton, New Jersey (J.V.S., Y.G.Y., R.H.); and Clinical Pharmacology and Pharmacometrics and Research and Early Development, Bristol Myers Squibb, Summit, New Jersey (P.Z., M.P., J.Q.T.).
Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [C]ozanimod hydrochloride to six healthy subjects.
View Article and Find Full Text PDFConcentration-QTc Modeling of Ozanimod's Major Active Metabolites in Adult Healthy Subjects.
CPT Pharmacometrics Syst Pharmacol
February 2021
Clinical Pharmacology and Pharmacometrics and Research and Early Development, Bristol Myers Squibb Company, Princeton, New Jersey, USA.
Ozanimod, approved by regulatory agencies in multiple countries for the treatment of adults with relapsing multiple sclerosis, is a sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity selectively to S1P receptor subtypes 1 and 5. The relationships between plasma concentrations of ozanimod and its major active metabolites, CC112273 and CC1084037, and the QTc interval (C-QTc) from a phase I multiple-dose study in healthy subjects were analyzed using nonlinear mixed effects modeling. QTc was modeled linearly as the sum of a sex-related fixed effect, baseline, and concentration-related random effects that incorporated interindividual and residual variability.
View Article and Find Full Text PDFMultiple-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites and the Pharmacodynamic and Pharmacokinetic Interactions with Pseudoephedrine, a Sympathomimetic Agent, in Healthy Subjects.
Adv Ther
December 2020
Clinical Pharmacology and Pharmacometrics and Research and Early Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.
Article Synopsis
- This study focused on understanding the pharmacokinetics (how the drug is processed in the body) of ozanimod's active metabolites and how it interacts with pseudoephedrine (PSE).
- Conducted as a phase 1 trial, 56 healthy volunteers received varying doses of ozanimod for 30 days, followed by a single dose of PSE to assess blood pressure changes and drug interactions.
- Results showed that ozanimod and its metabolites significantly contributed to drug exposure, but their combined use with PSE did not affect blood pressure or PSE's pharmacokinetics, indicating they were well-tolerated together.
Single-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites Alone and in Combination with Gemfibrozil, Itraconazole, or Rifampin in Healthy Subjects: A Randomized, Parallel-Group, Open-Label Study.
Adv Ther
October 2020
Clinical Pharmacology and Pharmacometrics and Research and Early Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.
Article Synopsis
- - The study aimed to explore the pharmacokinetics (PK) of ozanimod's major metabolites and how certain drugs (gemfibrozil, itraconazole, and rifampin) affect its PK in healthy individuals.
- - In a phase 1 trial, subjects received single doses of ozanimod (0.46 mg and 0.92 mg) under different conditions: with or without the aforementioned drugs, to assess their influence on the drug's absorption and metabolism.
- - Results showed that ozanimod and its metabolites displayed dose-dependent increases in concentration, with itraconazole slightly enhancing and rifampin reducing ozanimod's overall exposure, indicating the complex interactions at play in its metabolism.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!