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
Overview
- Phase
- Phase 1
- Intervention
- linaprazan glurate 25 mg QD
- Conditions
- GERD
- Sponsor
- Cinclus Pharma Holding AB
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- AUC0-24h Linaprazan (QD)
- Status
- Completed
- Last Updated
- 12 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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/m
- •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.
Arms & Interventions
Group 1: 25 mg linaprazan glurate QD
25 mg (one 25 mg oral tablet) linaprazan glurate once daily (QD) for 14 days
Intervention: linaprazan glurate 25 mg QD
Group 2: 50 mg Linaprazan Glurate QD
50 mg (two 25 mg oral tablets) linaprazan glurate once daily (QD) for 14 days
Intervention: linaprazan glurate 50 mg QD
Group 3: 75 mg Linaprazan Glurate QD
75 mg (three 25 mg oral tablet) linaprazan glurate once daily (QD) for 14 days
Intervention: linaprazan glurate 75 mg QD
Group 4: 25 mg Linaprazan Glurate BID
25 mg (one 25mg oral tablet) linaprazan glurate twice daily (BID) for 14 days
Intervention: linaprazan glurate 25 mg BID
Group 5: 50 mg Linaprazan Glurate BID
50 mg (two 25 mg oral tablets) linaprazan glurate twice daily (BID) for 14 days
Intervention: linaprazan glurate 50 mg BID
Group 6: 75 mg Linaprazan Glurate BID
75 mg (three 25 mg oral tablet) linaprazan glurate twice daily (BID) for 14 days
Intervention: linaprazan glurate 75 mg BID
Outcomes
Primary Outcomes
AUC0-24h Linaprazan (QD)
Time Frame: Day 1 and Day 14
Linaprazan area under the plasma concentration curve, from 0 to 24h post dose on Day 1 and Day 14. QD groups only.
AUC0-24h Linaprazan Glurate (QD)
Time Frame: Day 1 and day 14
Linaprazan glurate area under the plasma concentration curve, from 0-24h post dose on Day 1 and Day 14. QD groups only.
AUC0-12, 12-24h Linaprazan (BID)
Time Frame: Day 1 and Day 14
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.
Cmax Linaprazan (QD)
Time Frame: Day 1 and day 14
Linaprazan maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.
Cmax Linaprazan (BID)
Time Frame: Day 1 and day 14
Linaprazan maximum plasma concentration 0-12h, and 12-24h post dose for BID groups, at day 1 and day 14.
AUC0-12h, 12-24h Linaprazan Glurate (BID)
Time Frame: Day 1 and Day 14
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.
Cmax Linaprazan Glurate (QD)
Time Frame: Day 1 and day 14
Linaprazan glurate maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.
Cmax Linaprazan Glurate (BID)
Time Frame: Day 1 and day 14
Linaprazan glurate maximum plasma concentration 0-12h and 12-24h post dose for BID groups, at day 1 and day 14.
Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR)
Time Frame: Day 1 and day 14
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.