Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects

A Phase 1, Open Label, Randomized, Parallel-group, Single Center Study to Investigate Pharmacokinetics and Pharmacodynamics (Intragastric pH) of Linaprazan Glurate/Linaprazan After Single and 14 Days'Repeated Oral Administration of Linaprazan Glurate to Healthy Subjects

This is a Phase I, single-center, open label parallel-group, randomized study designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD, by continuous intragastric pH measurment), safety and tolerability of single and repeated oral doses of linaprazan glurate in 3 different dose levels given once- (QD) or twice daily (BID), for 14 days, with an additional single dose after 2, 4 or 6 days of drug holiday. The population will include healthy male and female subjects.

The subjects will be followed up to 28 days post IMP dosing.

Study Overview

• Status: Completed
• Conditions: GERD
• Intervention / Treatment: Drug: linaprazan glurate 25 mg QD; Drug: linaprazan glurate 50 mg QD; Drug: linaprazan glurate 75 mg QD; Drug: linaprazan glurate 25 mg BID; Drug: linaprazan glurate 50 mg BID; Drug: linaprazan glurate 75 mg BID

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • CRS d.o.o,Ukmarjeva ulica 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the study.
2. Healthy male or female subject aged 18 to 65 years, inclusive.
3. Body mass index ≥ 18.5 and ≤ 30.0 kg/m2.
4. 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:

1. Female subjects of childbearing potential (defined as all subjects physiologically capable of becoming pregnant)
2. Male subjects with a partner of childbearing potential
3. 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.
4. History of GERD or clinically significant acid reflux, as judged by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: 25 mg linaprazan glurate QD; 25 mg (one 25 mg oral tablet) linaprazan glurate once daily (QD) for 14 days	Drug: linaprazan glurate 25 mg QD; The subjects will receive 25 mg dose in the evening, in a non-fasted condition 30 minutes after the evening meal, for 14 days. Subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more in the evening (non-fasted).
Experimental: Group 2: 50 mg Linaprazan Glurate QD; 50 mg (two 25 mg oral tablets) linaprazan glurate once daily (QD) for 14 days	Drug: linaprazan glurate 50 mg QD; The subjects will receive 50 mg dose in the evening, in a non-fasted condition 30 minutes after the evening meal, for 14 days. Subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more in the evening (non-fasted).
Experimental: Group 3: 75 mg Linaprazan Glurate QD; 75 mg (three 25 mg oral tablet) linaprazan glurate once daily (QD) for 14 days	Drug: linaprazan glurate 75 mg QD; The subjects will receive 75 mg dose in the evening, in a non-fasted condition 30 minutes after the evening meal, for 14 days. Subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more in the evening (non-fasted).
Experimental: Group 4: 25 mg Linaprazan Glurate BID; 25 mg (one 25mg oral tablet) linaprazan glurate twice daily (BID) for 14 days	Drug: linaprazan glurate 25 mg BID; The subjects will receive 25 mg dose twice daily, in the morning and in the evening for 14 days. Subjects will be fasted for ≥10 hours overnight before dosing on Day 1 and day 14, until 30 minutes post-dose. During fasting, tap water, but no other drinks, are allowed as desired, except for 1 hour before and 30 minutes after dosing. The second daily dose will be administered 30 minutes after the evening meal, i.e. in a non-fasted condition. The subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more (in fasted condition in the morning, non-fasted in the evening).
Experimental: Group 5: 50 mg Linaprazan Glurate BID; 50 mg (two 25 mg oral tablets) linaprazan glurate twice daily (BID) for 14 days	Drug: linaprazan glurate 50 mg BID; The subjects will receive 50 mg dose twice daily, in the morning and in the evening for 14 days. Subjects will be fasted for ≥10 hours overnight before dosing on Day 1 and day 14, until 30 minutes post-dose. During fasting, tap water, but no other drinks, are allowed as desired, except for 1 hour before and 30 minutes after dosing. The second daily dose will be administered 30 minutes after the evening meal, i.e. in a non-fasted condition. The subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more (in fasted condition in the morning, non-fasted in the evening).
Experimental: Group 6: 75 mg Linaprazan Glurate BID; 75 mg (three 25 mg oral tablet) linaprazan glurate twice daily (BID) for 14 days	Drug: linaprazan glurate 75 mg BID; The subjects will receive 75 mg dose twice daily, in the morning and in the evening for 14 days. Subjects will be fasted for ≥10 hours overnight before dosing on Day 1 and day 14, until 30 minutes post-dose. During fasting, tap water, but no other drinks, are allowed as desired, except for 1 hour before and 30 minutes after dosing. The second daily dose will be administered 30 minutes after the evening meal, i.e. in a non-fasted condition. The subjects are to follow a standardized food intake schedule. After a drug holiday period of either 2, 4 or 6 days, linaprazan glurate will be given once more (in fasted condition in the morning, non-fasted in the evening).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-24h Linaprazan (QD)	Linaprazan area under the plasma concentration curve, from 0 to 24h post dose on Day 1 and Day 14. QD groups only.	Day 1 and Day 14
AUC0-12, 12-24h Linaprazan (BID)	Linaprazan area under the plasma concentration curve, from 0 to 12h and 12-24h post dose on Day 1 and Day 14. BID groups only.	Day 1 and Day 14
Cmax Linaprazan (QD)	Linaprazan maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.	Day 1 and day 14
Cmax Linaprazan (BID)	Linaprazan maximum plasma concentration 0-12h, and 12-24h post dose for BID groups, at day 1 and day 14.	Day 1 and day 14
AUC0-24h Linaprazan Glurate (QD)	Linaprazan glurate area under the plasma concentration curve, from 0-24h post dose on Day 1 and Day 14. QD groups only.	Day 1 and day 14
AUC0-12h, 12-24h Linaprazan Glurate (BID)	Linaprazan glurate area under the plasma concentration curve, from 0 to 12h and 12-24h post dose on Day 1 and Day 14. BID groups only.	Day 1 and Day 14
Cmax Linaprazan Glurate (QD)	Linaprazan glurate maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.	Day 1 and day 14
Cmax Linaprazan Glurate (BID)	Linaprazan glurate maximum plasma concentration 0-12h and 12-24h post dose for BID groups, at day 1 and day 14.	Day 1 and day 14
Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR)	Percentage of time gastric pH >4 at Days 1 and 14 over a 24-hour monitoring period following linaprazan glurate administration. Intragastric pH was measured every second with an intragastric probe. The measurements were compressed into 10-minute median intervalls before calculating the % of time with intragastric >pH 4 (HTR). The HTR is presented with descriptive statistics, by dosing group.	Day 1 and day 14

Collaborators and Investigators

• Sponsor: Cinclus Pharma Holding AB
• Investigators: Study Director: Tanja Turk, M.Pharm, CRS d.o.o Ljubljana, Ukmarjeva Ulica 6, Slovenia, 1000 Contact: Tanja Turk, M.pharm +38651619388 tanja.turk@crs.si

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2023
• Primary Completion (Actual): March 24, 2023
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: January 2, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CX842A2107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No