GERD
Conditions
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.
Interventions
DRUGlinaprazan 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).
DRUGlinaprazan 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).
DRUGlinaprazan 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).
DRUGlinaprazan 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).
DRUGlinaprazan 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).
DRUGlinaprazan 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).
Sponsors
Cinclus Pharma Holding AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-24h Linaprazan (QD) | 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. |
| AUC0-12, 12-24h Linaprazan (BID) | 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) | 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) | 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. |
| AUC0-24h Linaprazan Glurate (QD) | 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. |
| AUC0-12h, 12-24h Linaprazan Glurate (BID) | 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) | 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) | 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) | 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. |
Countries
Slovenia
Participant flow
Recruitment details
A total of 132 subjects were screened, of which 75 subjects were randomized, including 2 subjects who did not receive any study medication. Hence 73 subjects were randomized and received at least 1 dose of linaprazan glurate. Three subjects withdrew consent and 3 subjects discontinued due to adverse AEs. A total of 69 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| 25 mg Linaprazan Glurate QD 25 mg (one 25 mg oral tablet) linaprazan glurate QD for 14 days | 12 |
| 50 mg Linaprazan Glurate QD 50 mg (two 25 mg oral tablets) linaprazan glurate QD for 14 days | 13 |
| 75 mg Linaprazan Glurate QD 75 mg (three 25 mg oral tablets) linaprazan glurate QD for 14 days | 13 |
| 25 mg Linaprazan Glurate BID 25 mg (one 25mg oral tablet) linaprazan glurate BID for 14 days | 12 |
| 50 mg Linaprazan Glurate BID 50 mg (two 25 mg oral tablets) linaprazan glurate BID for 14 days | 11 |
| 75 mg Linaprazan Glurate BID 75 mg (three 25 mg oral tablets) linaprazan glurate BID for 14 days | 12 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 25 mg Linaprazan Glurate QD | Total | 75 mg Linaprazan Glurate BID | 50 mg Linaprazan Glurate BID | 25 mg Linaprazan Glurate BID | 75 mg Linaprazan Glurate QD | 50 mg Linaprazan Glurate QD |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 24.1 years STANDARD_DEVIATION 8.26 | 23.8 years STANDARD_DEVIATION 6.05 | 25.1 years STANDARD_DEVIATION 8.25 | 23.9 years STANDARD_DEVIATION 3.48 | 22.4 years STANDARD_DEVIATION 1.88 | 22.8 years STANDARD_DEVIATION 2.45 | 24.7 years STANDARD_DEVIATION 8.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 73 Participants | 12 Participants | 11 Participants | 12 Participants | 13 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 73 Participants | 12 Participants | 11 Participants | 12 Participants | 13 Participants | 13 Participants |
| Region of Enrollment Slovenia | 12 participants | 73 participants | 12 participants | 11 participants | 12 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 5 Participants | 32 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 41 Participants | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 6 / 12 | 8 / 13 | 6 / 13 | 7 / 12 | 6 / 11 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 11 | 1 / 12 |
Outcome results
Primary
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.
Time frame: Day 1 and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 1 | 4081 nmol/L*h | Standard Deviation 1351.9 |
| 25 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 1 | 3947 nmol/L*h | Standard Deviation 939.8 |
| 25 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 14 | 4896 nmol/L*h | Standard Deviation 1367.3 |
| 25 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 14 | 4002 nmol/L*h | Standard Deviation 1142.8 |
| 50 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 14 | 6334 nmol/L*h | Standard Deviation 2061.6 |
| 50 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 1 | 8084 nmol/L*h | Standard Deviation 1400.5 |
| 50 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 14 | 7518 nmol/L*h | Standard Deviation 1627 |
| 50 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 1 | 7107 nmol/L*h | Standard Deviation 1917.8 |
| 75 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 14 | 9609 nmol/L*h | Standard Deviation 2087.5 |
| 75 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC12-24h Day 1 | 9532 nmol/L*h | Standard Deviation 2118.1 |
| 75 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 14 | 11757 nmol/L*h | Standard Deviation 3058.3 |
| 75 mg Linaprazan Glurate QD | AUC0-12, 12-24h Linaprazan (BID) | AUC0-12h Day 1 | 11814 nmol/L*h | Standard Deviation 3181.8 |
Primary
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.
Time frame: Day 1 and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 1 | 40 nmol/L*h | Standard Deviation 15.5 |
| 25 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 1 | 30 nmol/L*h | Standard Deviation 14.6 |
| 25 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 14 | 39 nmol/L*h | Standard Deviation 23.2 |
| 25 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 14 | 28 nmol/L*h | Standard Deviation 10.2 |
| 50 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 14 | 68 nmol/L*h | Standard Deviation 38.1 |
| 50 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 1 | 117 nmol/L*h | Standard Deviation 65.3 |
| 50 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 14 | 69 nmol/L*h | Standard Deviation 37 |
| 50 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 1 | 74 nmol/L*h | Standard Deviation 40.7 |
| 75 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 14 | 114 nmol/L*h | Standard Deviation 91.2 |
| 75 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC 12-24h Day 1 | 78 nmol/L*h | Standard Deviation 24.7 |
| 75 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 14 | 156 nmol/L*h | Standard Deviation 140.6 |
| 75 mg Linaprazan Glurate QD | AUC0-12h, 12-24h Linaprazan Glurate (BID) | AUC0-12h Day 1 | 179 nmol/L*h | Standard Deviation 87.4 |
Primary
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.
Time frame: Day 1 and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 1 | 42 nmol/L*h | Standard Deviation 18.9 |
| 25 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 14 | 27 nmol/L*h | Standard Deviation 18.6 |
| 50 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 1 | 99 nmol/L*h | Standard Deviation 68 |
| 50 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 14 | 107 nmol/L*h | Standard Deviation 97.9 |
| 75 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 1 | 166 nmol/L*h | Standard Deviation 85.5 |
| 75 mg Linaprazan Glurate QD | AUC0-24h Linaprazan Glurate (QD) | AUC0-24h Day 14 | 149 nmol/L*h | Standard Deviation 201.1 |
Primary
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.
Time frame: Day 1 and Day 14
Population: Overall # of participants analyzed does not match the participant flow figures due a discrepancy between completers and evaluable participants (protocol deviations). Figures here represent the number of evaluable subjects.~NB! One participant in 50mg QD discontinued before completion of the full study, but only after the primary variables had been collected. Thus this participant's data was evaluable despite being a non-completer.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 1 | 5057 nmol/L*h | Standard Deviation 1650.6 |
| 25 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 14 | 4640 nmol/L*h | Standard Deviation 1657.4 |
| 50 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 1 | 8924 nmol/L*h | Standard Deviation 2281 |
| 50 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 14 | 8626 nmol/L*h | Standard Deviation 3571.9 |
| 75 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 1 | 13900 nmol/L*h | Standard Deviation 4339.5 |
| 75 mg Linaprazan Glurate QD | AUC0-24h Linaprazan (QD) | AUC0-24h Day 14 | 11697 nmol/L*h | Standard Deviation 4053.3 |
Primary
Cmax Linaprazan (BID)
Linaprazan maximum plasma concentration 0-12h, and 12-24h post dose for BID groups, at day 1 and day 14.
Time frame: Day 1 and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 1 | 658.42 nmol/L | Standard Deviation 212.101 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 1 | 520.92 nmol/L | Standard Deviation 126.378 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 14 | 782.92 nmol/L | Standard Deviation 263.988 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 14 | 520.83 nmol/L | Standard Deviation 144.568 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 14 | 842.36 nmol/L | Standard Deviation 270.396 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 1 | 1380.18 nmol/L | Standard Deviation 303.283 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 14 | 1148.64 nmol/L | Standard Deviation 415.251 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 1 | 997.09 nmol/L | Standard Deviation 363.66 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 14 | 1285.50 nmol/L | Standard Deviation 443.703 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 12-24h day 1 | 1283.90 nmol/L | Standard Deviation 435.399 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 14 | 1740.60 nmol/L | Standard Deviation 468.197 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (BID) | Cmax 0-12h day 1 | 1942.00 nmol/L | Standard Deviation 667.28 |
Primary
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.
Time frame: Day 1 and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 1 | 32.52 nmol/L | Standard Deviation 19.704 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 1 | 14.69 nmol/L | Standard Deviation 10.29 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 14 | 47.59 nmol/L | Standard Deviation 46.275 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 14 | 22.29 nmol/L | Standard Deviation 13.414 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 14 | 41.51 nmol/L | Standard Deviation 38.11 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 1 | 101.26 nmol/L | Standard Deviation 49.177 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 14 | 61.09 nmol/L | Standard Deviation 43.234 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 1 | 46.60 nmol/L | Standard Deviation 40.041 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 14 | 94.42 nmol/L | Standard Deviation 140.218 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax 12-24h Day 1 | 40.41 nmol/L | Standard Deviation 32.422 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 14 | 151.73 nmol/L | Standard Deviation 145.527 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (BID) | Cmax0-12h Day 1 | 148.19 nmol/L | Standard Deviation 80.799 |
Primary
Cmax Linaprazan Glurate (QD)
Linaprazan glurate maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.
Time frame: Day 1 and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 1 | 27.54 nmol/L | Standard Deviation 21.284 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 14 | 18.43 nmol/L | Standard Deviation 18.775 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 1 | 62.24 nmol/L | Standard Deviation 53.653 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 14 | 126.31 nmol/L | Standard Deviation 166.828 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 14 | 107.07 nmol/L | Standard Deviation 202.899 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan Glurate (QD) | Cmax Day 1 | 100.46 nmol/L | Standard Deviation 64.576 |
Primary
Cmax Linaprazan (QD)
Linaprazan maximum plasma concentration 0-24h post dose for QD groups, at day 1 and day 14.
Time frame: Day 1 and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 1 | 527.5 nmol/L | Standard Deviation 184.929 |
| 25 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 14 | 404.75 nmol/L | Standard Deviation 174.068 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 1 | 1066.23 nmol/L | Standard Deviation 209.973 |
| 50 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 14 | 1002.00 nmol/L | Standard Deviation 538.574 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 1 | 1594.42 nmol/L | Standard Deviation 585.525 |
| 75 mg Linaprazan Glurate QD | Cmax Linaprazan (QD) | Cmax day 14 | 1044.92 nmol/L | Standard Deviation 478.102 |
Primary
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.
Time frame: Day 1 and day 14
Population: PK/PD analysis set (PK/PDAS), a subset of the PK-analysis set, included all pH measurements which were evaluable. 4 subjects were excluded from the PK-analysis set, and thereby also from the PK/PDAS subset, due to study drug incompliance. Another 5 subjects were excluded entirely from the PK/PDAS due to presence of H. pylori (exclusion criteria - could have an impact on acid suppression sensitivity). In total 67 individuals provided at least 1 evaluable pH curve.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 48 % of time | Standard Deviation 23.23 |
| 25 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 48.5 % of time | Standard Deviation 30.62 |
| 50 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 64.6 % of time | Standard Deviation 13.33 |
| 50 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 63.9 % of time | Standard Deviation 20.09 |
| 75 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 68.1 % of time | Standard Deviation 23.48 |
| 75 mg Linaprazan Glurate QD | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 87.2 % of time | Standard Deviation 11.44 |
| 25 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 76.0 % of time | Standard Deviation 13.52 |
| 25 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 76.9 % of time | Standard Deviation 20.13 |
| 50 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 87.4 % of time | Standard Deviation 8.62 |
| 50 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 95.7 % of time | Standard Deviation 5.55 |
| 75 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 1 | 94.5 % of time | Standard Deviation 4.18 |
| 75 mg Linaprazan Glurate BID | Percentage of Time Gastric pH >4 Over a 24-hour Monitoring Period (Holding Time Ratio, HTR) | HTR (%) pH >4 day 14 | 99.0 % of time | Standard Deviation 1.54 |