Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects

Study Overview
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Brief Summary
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This is a Phase I, single-center, open label parallel-group, randomized study designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of single and repeated oral doses of Linaprazan Glurate for up to 14 days at 3 dose levels in healthy male and female subjects. The subjects will be followed up to 28 days post IMP dosing.

Official Title
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Ph 1, OL, Randomized, Parallel-group Study to Investigate PK and PD (Intragastric pH) of Linaprazan Glurate/Linaprazan After 14 Days Administration of Linaprazan Glurate to Healthy Subjects

Conditions
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GERD

Intervention / Treatment
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* Drug: Linaprazan Glurate 25 mg
* Drug: Linaprazan Glurate 50 mg
* Drug: Linaprazan Glurate 75 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give written informed consent for participation in the study. Healthy male or female subject aged 18 to 65 years, inclusive. Body mass index ≥ 18.5 and ≤ 30.0 kg/m2. Medically healthy, without abnormal clinically significant medical history, physical findings, vital signs, ECGs, or laboratory values at the time of screening, as judged by the Investigator. Exclusion Criteria: Female subjects of childbearing potential (defined as all subjects physiologically capable of becoming pregnant) Male subjects with a partner of childbearing potential History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. History of GERD or clinically significant acid reflux, as judged by the Investigator.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg Linaprazan Glurate QD<br>25 mg ( one 25 mg oral tablet) Linaprazan Glurate QD for 14 days | Drug: Linaprazan Glurate 25 mg<br>* The participating subjects will receive 25 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|
| Experimental: 50 mg Linaprazan Glurate QD<br>50 mg (two 25 mg oral tablets) Linaprazan Glurate QD for 14 days | Drug: Linaprazan Glurate 50 mg<br>* The participating subjects will receive 50 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|
| Experimental: 75 mg Linaprazan Glurate QD<br>75 mg ( three 25 mg oral tablet) Linaprazan Glurate QD for 14 days | Drug: Linaprazan Glurate 75 mg<br>* The participating subjects will receive 75 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|
| Experimental: 25 mg Linaprazan Glurate BID<br>25 mg ( one 25mg oral tablet) Linaprazan Glurate BID for 14 days | Drug: Linaprazan Glurate 25 mg<br>* The participating subjects will receive 25 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|
| Experimental: 50 mg Linaprazan Glurate BID<br>50 mg ( two 25 mg oral tablets) Linaprazan Glurate BID for 14 days | Drug: Linaprazan Glurate 50 mg<br>* The participating subjects will receive 50 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|
| Experimental: 75 mg Linaprazan Glurate BID<br>75 mg ( three 25 mg oral tablet) Linaprazan Glurate BID for 14 days | Drug: Linaprazan Glurate 75 mg<br>* The participating subjects will receive 75 mg doses of IMP, QD or BID for 14 days. After a drug holiday period (2, 4 or 6 days), linaprazan glurate will be given once more (QD or BID, on Day 16, 18 or 20). In total, 15 or 30 doses will be given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Area under the plasma concentration curve from 0 to infinity (AUCinf) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | AUC from time 0 to time 24 (AUC 0-24) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | AUC from time 0 to time 12 (AUC 0-12) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | AUC from time 12 to time 24 (AUC 12-24) | 12 hours, 14 hours, 20 hours, 24 hours | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | AUC from time 24 to time 48 (AUC 24-48) | 24 hours, 36 hours and 48 hours | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | AUC from time 0 to time t (AUC 0-t) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Trough plasma concentration (Ctrough) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Maximum plasma concentration (Cmax) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Average plasma concentration (Caver) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Terminal elimination half life (t½) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PK parameters after single and repeated administration of Linaprazan Glurate | Time of occurence of Cmax (Cmax (Tmax)) | pre dose, 0,25 hours, 0,5 hours, 1 hour, 1,25 hours, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 20 hours, 24 hours, 36 hours, 48 hours and 72 hours post dose | 
| Linaprazan Glurate and Linaprazan PD parameters after single and repeated administration of Linaprazan Glurate | Percentage of time gastric pH > 4 at Day 1, and Day 14 | 48 hours at Day 1 and 48 hours at Day 14 |