Delving into the Latest Updates on Odalasvir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ODV

+ [2]

Target

NS5A

Mechanism

NS5A inhibitors(Nonstructural protein 5A inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1Chronic hepatitis C genotype 1bChronic hepatitis C genotype 3+ [4]

Originator Organization

Alexion Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Janssen Research & Development LLC

Alios BioPharma, Inc.

Janssen Pharmaceuticals, Inc.

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC60H72N8O6

InChIKeyLSYBRGMTRKJATA-IVEWBXRVSA-N

CAS Registry1415119-52-6

The purpose of this study is to evaluate the pharmacokinetics (PK) of AL-335, odalasvir (ODV) and its metabolites ALS-022399 and ALS-022227, after a single oral dose of ODV and AL-335 respectively, in participants with moderately impaired hepatic function compared to participants with normal hepatic function. Also to evaluate the steady-state PK of AL-335 and its metabolites ALS-022399 and ALS-022227, ODV and simeprevir (SMV) after multiple oral doses of the combination of AL-335+ODV+SMV, in participants with moderately impaired hepatic function compared to participants with normal hepatic function.

Start Date11 Sep 2017

Sponsor / Collaborator

Janssen Research & Development LLC

NCT03155893 / CompletedPhase 1

A Randomized, Double-blind, Double-dummy, Placebo- and Positive-controlled Study to Evaluate the Cardiac Safety of a Single Dose of AL-335 Administered on a Background of Simeprevir and Odalasvir and of Repeated Doses of Odalasvir Administered Alone in Healthy Subjects

The main purpose of this study is to assess the effect of a single supratherapeutic dose of AL-335 administered on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo on QT/QT interval corrected for heart rate (QTc) interval changes, using intersection-union test (IUT) analysis (Panel 1); to assess the effect of ODV on QT/QTc and PR interval changes after multiple supratherapeutic doses of ODV using an exposure-response (ER) approach (Panel 2); and to assess the effect of multiple supratherapeutic doses of ODV on echocardiographic left ventricular ejection fraction (LVEF) (Panel 2) in healthy participants.

Start Date12 May 2017

Sponsor / Collaborator

Janssen Research & Development LLC

NCT03059303 / TerminatedPhase 1

Phase 1, Open-label, Partially Randomized, Parallel-group Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Single-dose Simeprevir (SMV), Odalasvir (ODV), and AL-335 Administered as a Fixed-dose Combination (FDC) Compared With the Single Agents Administered Together, and to Assess the Effect of Multiple-dose Lansoprazole or Omeprazole on the Single-dose Pharmacokinetics of SMV, ODV, and AL-335 Administered as an FDC

The purpose of this study is to assess the relative bioavailability of single-dose Simeprevir (SMV), Odalasvir (ODV), and AL-335 when administered as a fixed-dose combination (FDC) compared with the single agents when administered together, and to assess the effect of multiple-dose lansoprazole and omeprazole on the single-dose pharmacokinetics (PK) of SMV, ODV, and AL-335 when administered as an FDC.

Start Date20 Feb 2017

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with Odalasvir

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100 Translational Medicine associated with Odalasvir

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100 Patents (Medical) associated with Odalasvir

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95

Literatures (Medical) associated with Odalasvir

01 Jun 2024·Journal of Pharmaceutical and Biomedical Analysis

Multiplexed quantification of venlafaxine and metabolites in human plasma by liquid chromatography-tandem mass spectrometry

Article

Author: Ayala-Lopez, Nadia ; Price, Amelia ; Knezevic, Claire E ; Garza, Kyana Y ; Marzinke, Mark A ; Pandey, Aashish

BACKGROUNDVenlafaxine (VEN) and its O-demethylated metabolite, O-desmethylvenlafaxine (ODV), are commonly prescribed serotonin-norepinephrine reuptake inhibitors, approved for the treatment of depression and anxiety. Both are metabolized to inactive metabolites via cytochrome P450 enzymes. While previous studies have focused on quantifying VEN and ODV, bioanalytical methods for the simultaneous measurement of all metabolites are needed to fully characterize the pharmacology of VEN and ODV.METHODSK₂EDTA plasma was spiked with VEN, ODV, N-desmethylvenlafaxine (NDV), N,O-didesmethylvenlafaxine (NODDV), and N,N-didesmethylvenlafaxine (NNDDV). Drugs and metabolites were extracted via protein precipitation and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The multiplexed assay was validated in accordance with regulatory recommendations, and evaluated in remnant plasma samples from persons prescribed venlafaxine.RESULTSThe analytical measuring range for venlafaxine and all four metabolites was 5-800 ng/mL. Standard curves were generated via weighted quadratic (NNDDV) or linear (VEN, ODV, NDV, NODDV) regression of calibrators. Inter-assay imprecision was between 1.9-9.3% for all levels of all analytes. Minor matrix effects were observed, and both recovery efficiency and process efficiency were >96% for all analytes. All other assay validation assessments met acceptance criteria. Drug concentrations measured from remnant plasma specimens obtained from patients with current venlafaxine prescriptions (37.5-450 mg/day) yielded NDDV, NDV, and NODDV metabolite concentrations in 6/21, 14/21, and 20/21 samples, respectively. The ratio of active to inactive analytes ranged from 0.74 to 14.5, with a median of 6.39.CONCLUSIONSAn efficient and accurate LC-MS/MS method was developed and validated for the quantification of VEN, ODV, and all three inactive metabolites in plasma. The assay met all acceptance criteria, and may be used in future studies of the pharmacokinetics of these drugs.

01 Apr 2024·Therapeutic Drug Monitoring

A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round

Article

Author: Decheiver, Sarah ; Fikanni, Amine ; N'Zoué Kanga, Sita ; Tifrea, Andrea ; Pihan, Franck ; Tifrea, Marius ; Flint, Harry ; Vandroux, David ; Marsaud, Jean-Philippe ; Couderc, Sylvain ; Sahar, Abdallah ; Gabriel, Anthony

Background:This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood.Methods and Results:Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L.Conclusions:This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.

01 Apr 2024·Pharmaceutical Research

Physiologically Based Pharmacokinetic Modeling to Unravel the Drug-gene Interactions of Venlafaxine: Based on Activity Score-dependent Metabolism by CYP2D6 and CYP2C19 Polymorphisms

Article

Author: Yang, Hongyi ; Zhang, Wei ; Xie, Haitang ; Shen, Chaozhuang ; Zheng, Liang ; Shao, Wenxin ; Wang, Ling ; Jiang, Xuehua

BACKGROUNDVenlafaxine (VEN) is a commonly utilized medication for alleviating depression and anxiety disorders. The presence of genetic polymorphisms gives rise to considerable variations in plasma concentrations across different phenotypes. This divergence in phenotypic responses leads to notable differences in both the efficacy and tolerance of the drug.PURPOSEA physiologically based pharmacokinetic (PBPK) model for VEN and its metabolite O-desmethylvenlafaxine (ODV) to predict the impact of CYP2D6 and CYP2C19 gene polymorphisms on VEN pharmacokinetics (PK).METHODSThe parent-metabolite PBPK models for VEN and ODV were developed using PK-Sim^® and MoBi^®. Leveraging prior research, derived and implemented CYP2D6 and CYP2C19 activity score (AS)-dependent metabolism to simulate exposure in the drug-gene interactions (DGIs) scenarios. The model's performance was evaluated by comparing predicted and observed values of plasma concentration-time (PCT) curves and PK parameters values.RESULTSIn the base models, 91.1%, 94.8%, and 94.6% of the predicted plasma concentrations for VEN, ODV, and VEN + ODV, respectively, fell within a twofold error range of the corresponding observed concentrations. For DGI scenarios, these values were 81.4% and 85% for VEN and ODV, respectively. Comparing CYP2D6 AS = 2 (normal metabolizers, NM) populations to AS = 0 (poor metabolizers, PM), 0.25, 0.5, 0.75, 1.0 (intermediate metabolizers, IM), 1.25, 1.5 (NM), and 3.0 (ultrarapid metabolizers, UM) populations in CYP2C19 AS = 2.0 group, the predicted DGI AUC_0-96 h ratios for VEN were 3.65, 3.09, 2.60, 2.18, 1.84, 1.56, 1.34, 0.61, and for ODV, they were 0.17, 0.35, 0.51, 0.64, 0.75, 0.83, 0.90, 1.11, and the results were similar in other CYP2C19 groups. It should be noted that PK differences in CYP2C19 phenotypes were not similar across different CYP2D6 groups.CONCLUSIONSIn clinical practice, the impact of genotyping on the in vivo disposition process of VEN should be considered to ensure the safety and efficacy of treatment.

100 Deals associated with Odalasvir

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Odalasvir	-	DB13041

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C, Chronic	Phase 3	PL	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	PL	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	NZ	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	CA	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	SG	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	SG	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	CA	Janssen Research & Development LLC	10 Apr 2017
Hepatitis C, Chronic	Phase 3	NZ	Janssen Research & Development LLC	10 Apr 2017
Chronic hepatitis C genotype 3	Phase 3	NZ	Alios BioPharma, Inc.	31 Oct 2015
Chronic hepatitis C genotype 1	Phase 3	-	Alexion Pharmaceuticals, Inc.	01 Apr 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02993250 (OMEGA-3, CTgov)	Phase 2	Fibrosis \| Hepatitis C, Chronic \| Compensated cirrhosis	33	odalasvir (ODV)+AL-335 (Cohort 1: Chronic Hepatitis C Without Cirrhosis)	foztfhhztd(ynznidijre) = zcxfcojvrc ponmirelzx (zjanvvgfis, msdqrzlckx - tvwmqpnefv) View more	-	11 Sep 2019
				SMV+ODV+AL-335 (Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis)	foztfhhztd(ynznidijre) = cxowpvuncc ponmirelzx (zjanvvgfis, ghgyuqjaor - umoenhqxms) View more
NCT02765490 (OMEGA-1, CTgov)	Phase 2	Hepatitis C, Chronic	365	SMV+ODV+AL-335 (Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks)	apiyajrkuv(qoujootbkh) = rdhafflstg xxtmkaeout (owtvrrqmzn, qqfqligtlv - gicwoheixq) View more	-	22 Jan 2019
				SMV+ODV+AL-335 (Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks)	apiyajrkuv(qoujootbkh) = poadvmxbxg xxtmkaeout (owtvrrqmzn, antbfwdlrb - mimlakuyxx) View more
NCT01849562 (CTgov)	Phase 2	Chronic hepatitis C genotype 1	30	Placebo	hcvtjiidbn(klevaswrdq) = ksnzqlxqse hnuzkovhbk (hcmczkxnxq, pqjkmsklnn - xtbgohbmsc) View more	-	04 Feb 2015