Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Vonoprazan · 11 trials · 10 indications
Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Diary day was considered heartburn-free if both morning and evening diary entries were heartburn-free and there was no reported use of rescue antacid, H2RAs, or PPIs.
H pylori eradication was determined by the \^13C-UBT test.
A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.
A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.
An evaluable heartburn episode was an episode for which study drug was taken and for which the participant completed at least one entry in the heartburn episode diary. For a heartburn episode to be considered completely relieved, a participant must not have taken rescue antacid within 3 hours of taking study drug. For sustained relief, complete relief must have been accompanied by 24 hours without another heartburn episode after taking study drug.
AUC from time 0 to 24 hours post-dose, calculated as: the sum of the product of the concentration of the interval and the width of the interval.
Maximum observed concentration after dosing.
Minimum observed concentration after dosing.
Average concentration, calculated as: AUC0-24/tau (tau=the difference between the end time of the last interval and dosing time).
Time to maximum observed concentration (actual midpoint of the interval in which Cmax was observed).
Plasma pharmacokinetic (PK) parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. Data presented based on collections on both Day 7 and Day 14.
Plasma PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. Data presented based on collections on both Day 7 and Day 14.
Oral PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. Data presented based on collections on both Day 7 and Day 14.
Plasma PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time. Data presented based on collections on both Day 7 and Day 14.
Plasma pharmacokinetic (PK) parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.
PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.
Calculated as: Time pH \>4\*100/total actual monitoring period time. Gastric pH was measured continuously over a 24-hour period on Days 1 and 7 of Periods 1 and 2, using a pH and pressure sensitive probe and ambulatory pH recording system. A pH recording was taken every second.
The average gastric pH was a measure of the immediate effect on gastric pH and the duration of effect on gastric pH. Gastric pH was measured continuously over a 24-hour period on Days 1 and 7 of Periods 1 and 2, using a pH and pressure sensitive probe and ambulatory pH recording system. A pH recording was taken every second. The pH scale ranges from 0 to 14 with values below 7 being more acidic and values above 7 being more basic. Normal gastric pH is between 1.5 and 3.5.
Calculated using the Linear Trapezoidal with Linear Interpolation Method. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Calculated as the area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) + (Clast/Kel) where Clast is the last observed/measured concentration and Kel is the apparent first-order terminal elimination rate constant. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Cmax was taken directly from bioanalytical data. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Taken from the clinical database as the difference in the time of administration and the time of the blood draw which was associated with the Cmax. If the maximum value occurred at more than one time point, Tmax was defined as the first time point with this value. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Calculated using the Linear Trapezoidal with Linear Interpolation Method. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Cmax,ss was taken directly from bioanalytical data. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
Taken from the clinical database as the difference in the time of administration and the time of the blood draw which was associated with the Cmax,ss. The analyses of vonoprazan and lansoprazole in plasma samples was performed using validated liquid chromatography-mass spectrometry/mass spectrometry methods.
AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
AUC0-inf was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Cmax was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
| Arm | Type | Description |
|---|---|---|
| Vonoprazan 10 mg | EXPERIMENTAL | Participants will be administered vonoprazan at a dose of 10 mg QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to vonoprazan 10 mg in the Placebo-controlled Treatment Period will continue to take the same dose in the 20 week Extension Period. |
| Vonoprazan 20 mg | EXPERIMENTAL | Participants will be administered vonoprazan at a dose of 20 mg QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to vonoprazan 20 mg in the Placebo-controlled Treatment Period will continue to take the same dose in the 20 week Extension Period. |
| Placebo | PLACEBO_COMPARATOR | Participants will be administered the placebo QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to placebo in the Placebo-controlled Treatment Period will be re-randomized to receive either vonoprazan 10 mg QD or vonoprazan 20 mg QD in the 20 week Extension Period. |
| Vonoprazan dual therapy | EXPERIMENTAL | Participants will receive vonoprazan 20 mg twice daily (BID) in conjunction with amoxicillin 1 g, three times daily, for 14 days. |
| Vonoprazan triple therapy | EXPERIMENTAL | Participants will receive vonoprazan 20 mg twice daily (BID) in conjunction with amoxicillin 1 g BID and clarithromycin 500 mg, BID, for 14 days. |
| Lansoprazole triple therapy | ACTIVE_COMPARATOR | Participants will receive lansoprazole 30 mg twice daily (BID) in conjunction with amoxicillin 1 g BID and clarithromycin 500 mg BID, for 14 days. |
| Healing Phase: Vonoprazan 20 mg | EXPERIMENTAL | Participants will receive oral vonoprazan 20 mg once per day (QD) for a maximum of 8 weeks. |
| Healing Phase: Lansoprazole 30 mg | ACTIVE_COMPARATOR | Participants will receive oral lansoprazole 30 mg once per day (QD) for a maximum of 8 weeks. |
| Maintenance Phase: Vonoprazan 10 mg | EXPERIMENTAL | Participants will receive oral vonoprazan 10 mg once per day (QD) for a maximum of 24 weeks. |
| Maintenance Phase: Vonoprazan 20 mg | EXPERIMENTAL | Participants will receive oral vonoprazan 20 mg once per day (QD) for a maximum of 24 weeks. |
| Maintenance Phase: Lansoprazole 15 mg | ACTIVE_COMPARATOR | Participants will receive oral lansoprazole 15 mg once per day (QD) for a maximum of 24 weeks. |
| Run-In Period | EXPERIMENTAL | Participants will receive vonoprazan 20 mg once daily for up to 4 weeks. |
| Vonoprazan 10 mg: On-Demand Treatment Period | EXPERIMENTAL | Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 10 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period. |
| Vonoprazan 20 mg: On-Demand Treatment Period | EXPERIMENTAL | Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 20 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period. |
| Vonoprazan 40 mg: On-Demand Treatment Period | EXPERIMENTAL | Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 40 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period. |
| Placebo: On-Demand Treatment Period | PLACEBO_COMPARATOR | Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take a placebo when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period. |
| Vonoprazan 20 mg Once Daily | EXPERIMENTAL | Participants will be administered once-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4). |
| Vonoprazan 20 mg Twice Daily | EXPERIMENTAL | Participants will be administered twice-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4). |
| Vonoprazan 10mg | EXPERIMENTAL | Participants will receive vonoprazan 10mg QD for 14 days. |
| Vonoprazan 20mg | EXPERIMENTAL | Participants will receive vonoprazan 20mg QD for 14 days. |
| Treatment Sequence 1 | EXPERIMENTAL | Participants assigned to Treatment Sequence 1 will receive vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 1, vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 2, and vonoprazan 20 mg as a tablet on Day 1 of Treatment Period 3. |
| Treatment Sequence 2 | EXPERIMENTAL | Participants assigned to Treatment Sequence 2 will receive vonoprazan 20 mg as a tablet on Day 1 of Treatment Period 1, vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 2, and vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 3. |
| Treatment Sequence 3 | EXPERIMENTAL | Participants assigned to Treatment Sequence 3 will receive vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of applesauce on Day 1 of Treatment Period 1, vonoprazan 20 mg as a tablet on Day 1 of Treatment Period 2, and vonoprazan 20 mg as a sprinkle capsule on 1 tablespoon of pudding on Day 1 of Treatment Period 3. |
| Treatment A (vonoprazan) | EXPERIMENTAL | Participants will be randomized to receive vonoprazan (treatment A) and lansoprazole (treatment B) in a two period sequence, following either treatment sequence AB or BA. There will be a washout period of at least 7 days between Period 1 and Period 2. Vonoprazan will be administered via 20 mg oral tablet once daily on Day 1 through to Day 7 in a period, where each period is up to 8 days. |
| Treatment B (lansoprazole) | ACTIVE_COMPARATOR | Participants will be randomized to receive vonoprazan (treatment A) and lansoprazole (treatment B) in a two period sequence, following either treatment sequence AB or BA. There will be a washout period of at least 7 days between Period 1 and Period 2. Lansoprazole will be administered via 30 mg oral capsule once daily on Day 1 through to Day 7 in a period, where each period is up to 8 days. |
| Midazolam single doses / Vonoprazan multiple doses | EXPERIMENTAL | Single oral doses of 2 mg of midazolam syrup on Day 1 and Day 9 and twice daily (BID) doses of 20 mg vonoprazan oral tablets on Days 2 through 10 |
| Name | Type | Description |
|---|---|---|
| Vonoprazan | DRUG | Orally via capsule |
| Placebo | DRUG | Orally via capsule |
| Amoxicillin | DRUG | Capsules administered orally. |
| Clarithromycin | DRUG | Tablets administered orally. |
| Lansoprazole | DRUG | Over-encapsulated capsules administered orally. |
| Midazolam | DRUG | 2 mg syrup administered orally |
Inclusion Criteria: 1. The participant is ≥18 years of age at the time of informed consent signing. 2. In the opinion of the investigator or subinvestigators, the participant is capable of understanding and complying with protocol requirements, including compliance with the electronic diary. 3. The...