A Study to Investigate the Pharmacokinetics and ECG Effects of Linaprazan Glurate

Study Overview
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Brief Summary
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This is a Phase I, single-center, double blind, placebo-controlled, parallel-group, randomized study designed to evaluate the PK, cardiodynamic ECG effects, safety, and tolerability of 2 single ascending oral doses of linaprazan glurate. The study will explore the PK properties of linaprazan glurate and linaprazan as well as the cardiodynamic ECG effects, safety, and tolerability after the administration of single doses (300 mg, 600 mg, 200 mg and a final dose level of maximum 400 mg) of linaprazan glurate, using 25 mg base formulation (300 mg and 600 mg doses) and 25 mg and 100 mg HCl formulation (200 mg and final dose level of maximum 400 mg) oral tablets.

Official Title
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A Phase I Study to Investigate the Pharmacokinetics and ECG Effects of Two Single Ascending Doses of Linaprazan Glurate Given as Oral Tablets to Healthy Subjects

Conditions
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Cardiodynamic ECG, Pharmacokinetics, Safety, and Tolerability, GERD

Intervention / Treatment
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* Drug: Linaprazan glurate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main inclusion Criteria: Willing and able to give written informed consent for participation in the study. Healthy male or female aged 18 to 65 years Body mass index ≥18.5 and ≤35.0 kg/m2. Prospective subjects, as well as their partners, must agree to contraception requirements Main exclusion criteria: Female subjects of childbearing potential unless they agree to use highly effective methods of contraception (failure rate of <1%) from 2 weeks prior to dosing until the end-of-study visit. Male subjects with a partner of childbearing potential, unless they agree to use method of contraception from 2 weeks prior to dosing until the end-of-study visit.History of or current clinically significant disease as defined in the protocol History of or current clinically significant disease as defined in the protocol. History of GERD, significant acid reflux. Subjects who are pregnant, currently breastfeeding, or intend to become pregnant (female subjects) or father a child (male subjects) during the course of the study (i.e., from screening to end of study visit).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linaprazan glurate<br>Oral administration as a single dose of 300 mg, 600 mg, 200 mg, and a final dose level of maximum 400 mg. | Drug: Linaprazan glurate<br>* Linaprazan glurate base formulation, 25 mg oral tablets (300 mg and 600 mg doses). Linaprazan glurate hydrochloride (HCl), 25 mg and 100 mg (as base) oral tablets (200 mg and final dose level of maximum 400 mg).<br>* Other names: X842;|
| Placebo Comparator: Placebo<br>Oral administration as a singel dose | Drug: Placebo<br>* Single dose, oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUCinf) | To assess the Area under the plasma concentration vs. time curve (AUC) from time 0 to infinity (AUCinf) | Up to 24 hours | 
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUClast) | To assess the AUC from time 0 to the last measurable concentration (AUClast) | Up to 24 hours | 
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (Cmax) | To assess the Maximum plasma concentration (Cmax) | Up to 24 hours | 
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (T1/2) | To assess the Terminal elimination half-life (T1/2) | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (QTcF) | To assess the change from baseline in QTcF | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (heart rate) | To assess the change from baseline in heart rate | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (PR interval) | To assess the change from baseline in PR interval | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (QRS interval) | To assess the change from baseline in QRS interval | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (placebo-corrected QTcF) | To assess the change from baseline in placebo-corrected QTcF | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (placebo-corrected heart rate) | To assess the change from baseline in placebo-corrected heart rate | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (placebo-corrected PR interval) | To assess the change from baseline in placebo-corrected PR interval | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (placebo-corrected QRS interval) | To assess the change from baseline in placebo-corrected QRS interval | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (categorical outliers) | Number of categorical outliers for ECG parameters (QTcF, HR, PR interval, QRS interval) | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (changes of T-wave) | Frequency of treatment emergent changes of T-wave abnormalities | Up to 24 hours | 
| Measurement of Cardiodynamic ECG (changes of U-wave) | Frequency of treatment emergent changes of U-wave abnormalities | Up to 24 hours |