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Clinical development

Follow the progress and further development of linaprazan glurate

Clinical development

The ongoing clinical development and testing of linaprazan glurate is showing promising results in acid control and in lowering the Cmax-value. Follow the progress and further development.

Phase II studies were initiated in Q3 2021, within a de-risked clinical development program based on experience from precedent trials on its active metabolite linaprazan. Linear response and excellent biomarker are significant results from the completed Phase I studies. These results form a base for predicting the frequency of healing of esophagitis in Phase II. The start of Phase III is planned for 2023.

Clinical trials on linaprazan glurate – Phase I to Phase III


Phase I

Phase I was initiated in February 2017 and recruitment was finalized Q4 2017. Three phase I clinical trials are completed. All three phase I studies showed that linaprazan glurate is safe and well tolerated.


Phase II

Phase II was initiated in H2 2021 within a de-risked clinical development program. The scope of the test is: to select the optimal dose for the phase III studies, based on dose dependent healing rates of erosive esophagitis.

The program is based on:

  • Precedent trials on the active metabolite of linaprazan glurate and includes ~2,500 subjects

  • Excellent Biomarker available

  • Linear correlation between plasma concentration and acid control


Phase III

Phase III is to be initiated in 2023.


Studies performed on linaprazan (the main metabolite)

Comprehensive data from 23 phase I studies including more than 600 subjects and two Phase II studies including approximately 2000 patients shows that linaprazan was well tolerated, with a fast onset of action and full effect at first dose. Linprazane is the active metabolite of linaprazan glurate.


Phase I – three studies completed

Linear response and excellent biomarker are significant results from the completed Phase I studies.

Dose dependent pH control


linaprazan glurate - liquid formulation


Overview of SAD/MAD study

Study of single ascending dose (SAD) and Multiple ascending dose (MAD) performed in Sweden.


Primary objective and results

Linaprazan glurate was safe and well tolerated. No serious adverse event (SAE) occurred after dosing.

  • Dose linear pharmacokinetics

  • Dose linear acid inhibition and clear PK/PD relationship

  • No effect of food was detected

  • Study Maximum Dose was reached

  • Gastric acid inhibition was maintained over 24 hours at certain dose levels


Description

  • Single and multiple ascending dose

  • Liquid formulation

  • First-in-human design

  • Gov. identifier: NCT03105375


Endpoints

  • Frequency of adverse events, lab results and vital signs

  • Standard PK parameters

  • Dose limiting toxicity

  • PK/PD where PD is intragastric pH over 24h


Number of patients

  • In total, 28 subjects were treated of which 9 subjects were treated more than once

  • Performed at CTC Uppsala Sweden


Timetable

Initiated in February 2017. Final study report in February 2018.


Phase II design (onging)

 

Primary objective

The primary objective of the study is to support dose selection of linaprazan glurate for Phase III studies based on four weeks healing of esophagitis.


Secondary objective

  • Evaluate the safety and tolerability of linaprazan glurate compared to standard PPI

  • Compare the symptom response after four weeks with three dose levels of linaprazan glurate compared to standard PPI

  • Model the optimal dose of linaprazan glurate using healing rates and PK data in patients treated with linaprazan glurate


Description

A multi-center, randomized, double-blind, active comparator-controlled, parallel group design study with four arms conducted in patients with reflux esophagitis grade C and D and patients still unhealed after four weeks standard treatment healing course with PPI.


Endpoints

  • The primary endpoint is the healing rates of eGERD after four weeks treatment

  • Evaluate the safety and tolerability of linaprazan glurate

  • Symptom response during and after four weeks

  • Model the optimal dose of linaprazan glurate for phase 


Number of patients

  • At least 200 evaluable patients

  • Approximately 60 sites

  • Approximately 10 countries in Europe and US


Timetable

First patient first visit (FPFV) in H2 2021 and Last patient last visit (LPLV) in summer 2022.