Delving into the Latest Updates on YH-4808 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ATPase

Mechanism

ATPase inhibitors(ATPase inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication-

Inactive Indication

Esophagitis, Peptic

Originator Organization

Yuhan Corp.

Active Organization-

Inactive Organization

Yuhan Corp.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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AbstractYH4808 is a novel potassium‐competitive acid blocker that is under clinical development to treat patients with gastroesophageal reflux disease and peptic ulcer diseases. In this study, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of YH4808 were modeled in healthy male volunteers who received a single oral dose of YH4808 at 30, 50, 100, 200, 400, 600, and 800 mg or matching placebo and multiple once‐daily oral doses of YH4808 at 100, 200, and 400 mg or matching placebo for 7 days. A population PK–PD model adequately described the time–concentration‐effect profiles of YH4808. The maximum increasing effect of YH4808 on intragastric pH was 4.38, which was higher than the observed maximum increase in intragastric pH after omeprazole at 40 mg (2.2 in pH). The maximum inhibitory effect by the increased intragastric pH on the exposure to repeated YH4808 was 58% from baseline. Monte–Carlo simulation experiments based on the final model showed that YH4808 at 200 mg will produce a higher percentage of time at pH > 4 over 24 h on day 1 than observed value of esomeprazole at 40 mg once‐daily, an active comparator (84.7% time vs. 58.3% time, respectively). Because YH4808 at ≥200 mg resulted in a higher percentage of time at intragastric pH > 4 than seen after once‐daily esomeprazole at 40 mg and YH4808 showed acceptable tolerability at a single‐dose of 30–800 mg, we suggest to test the 200 mg once daily dosage regimen in further clinical trials of YH4808.

01 Jan 2021·Translational and Clinical Pharmacology

Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen

Article

Author: Kim, Choon Ok ; Oh, EunSil ; Yoon, Sukyong ; Park, Min Soo ; Park, Hyeonsoo ; Jang, Seong Bok ; Byun, Hae Mi ; Kim, Heeyoung

YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control. This study was performed in two parts. Each was a randomized, open-label, active-controlled, multiple-doses, two-treatment, two-period crossover study conducted in 20 healthy Korean volunteers. Subjects were randomly assigned to one of the four groups. The three groups received different dosage regimens of YH4808 (100 mg twice a day, 200 mg once a day, or 200 mg twice a day), and the fourth group received esomeprazole 40 mg twice a day. The pharmacokinetic parameters demonstrated that the systemic exposure of YH4808 increased in a dose-proportional manner. The difference in the proportion of time above pH 4 over 24 h from the baseline was the greatest in the group receiving YH4808 200 mg twice a day. The values of the area under the effect curve at night time (12 A.M.-7 A.M.) were higher in all YH4808 groups than in the esomeprazole group. However, the differences among the YH4808 groups were not statistically significant (p > 0.05). YH4808 exhibited potential for better pH control during the night in comparison to esomeprazole. The optimal regimen for night time pH control among all the YH4808 regimens was 200 mg twice a day.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01761513.

01 Mar 2019·European Journal of Pharmaceutical SciencesQ2 · MEDICINE

A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of YH4808, a novel K+-competitive acid blocker

Q2 · MEDICINE

Article

Author: Lee, Hyun A ; Lee, Kyeong-Ryoon ; Chung, Soo Yong ; Yu, Kyung-Sang ; Lee, Howard ; Hyun A. Lee ; Jang, Seong Bok

A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans. The pharmacokinetic profiles of YH4808 after multiple oral administrations were predicted using a refined PBPK model. The ratios of model-predicted to observed C_max, AUC_inf and AUC_τ values on Day 1 and Day 7 at 100 mg were 0.7-1.0. However, the model failed to predict a decreased exposure after multiple oral administration particularly at higher doses of 200 and 400 mg. The reduced solubility of YH4808 at higher pH was hypothesized as the main cause of the reduction in exposure such that absorption was decreased as pH was increased. This hypothesis was confirmed by PBPK modeling and simulation, where intragastric pH was increased by YH4808.

100 Deals associated with YH-4808

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophagitis, Peptic	Phase 2	KR	Yuhan Corp.	01 Dec 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01921647 (Pubmed)	Phase 1	Helicobacter pylori infection	60	YH4808, amoxicillin, and clarithromycin	(njztlasdef) = mqpnqwwdkf kfgkfmzvoe (qeutwshggn )	-	01 Sep 2020
				YH4808 and amoxicillin	(njztlasdef) = vnjeyscugu kfgkfmzvoe (qeutwshggn )