Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis
Conditions
Brief summary
The purpose of this survey is to evaluate the safety and effectiveness of vonoprazan tablets in patients with gastric ulcer, duodenal ulcer, and reflux esophagitis in the routine clinical setting.
Detailed description
The drug being tested in this survey is called vonoprazan. Vonoprazan is being tested to treat patients who have gastric ulcer, duodenal ulcer, and reflux esophagitis. This survey will look at the safety and effectiveness of vonoprazan in patients with gastric ulcer, duodenal ulcer, and reflux esophagitis in the routine clinical setting. The survey will enroll approximately 3000 participants. \- Vonoprazan 20 mg This multi-center survey will be conducted in Japan.
Interventions
DRUGVonoprazan
Vonoprazan tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
\- Participants with gastric ulcer, duodenal ulcer, and reflux esophagitis
Exclusion criteria
* Participants with previous history of hypersensitivity to ingredients in Takecab tablets * Participants taking atazanavir sulfate or rilpivirine hydrochloride * Participants meeting the criteria of scarring stage (S1, S2) of endoscopic classification defined by Sakita and Miwa at the start of the treatment with Takecab tablets, in the case that the target disease is gastric ulcer or duodenal ulcer * Participants meeting the criteria of Grade N or Grade M of Los Angeles classification (Hoshihara's modification) at the start of the treatment with Takecab tablets, in the case that the target disease is reflux esophagitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Gastric Ulcer Who Had One or More Adverse Drug Reactions | Up to 8 weeks | An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug. |
| Percentage of Participants With Duodenal Ulcer Who Had One or More Adverse Drug Reactions | Up to 6 weeks | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug. |
| Percentage of Participants With Reflux Esophagitis Who Had One or More Adverse Drug Reactions | Up to 8 weeks | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Baseline and at the end of the survey (up to 8 weeks) | Percentage of participants who treated for gastric ulcer and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved. |
| Endoscopic Cure Rate in Participants With Gastric Ulcer | Up to 8 weeks | Endoscopic cure rate was defined as a percentage of participants treated for gastric ulcer who classified as Scarring stage at the end of survey per Sakita-Miwa Classification. Endoscopic findings of ulcer were classified per Sakita-Miwa Classification as follows; Active stage: A1 and A2, Healing stage: H1 and H2, Scarring stage: S1 and S2. |
| Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Baseline and at the end of the survey (up to 8 weeks) | Percentage of participants who treated for reflux esophagitis and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved. |
| Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Baseline and at the end of the survey (up to 6 weeks) | Percentage of participants who treated for duodenal ulcer and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved. |
| Endoscopic Cure Rate in Participants With Duodenal Ulcer | Up to 6 weeks | Endoscopic cure rate was defined as a percentage of participants treated for duodenal ulcer who classified as Scarring stage at the end of survey per Sakita-Miwa Classification. Endoscopic findings of ulcer were classified per Sakita-Miwa Classification as follows; Active stage: A1 and A2, Healing stage: H1 and H2, Scarring stage: S1 and S2. |
| Endoscopic Cure Rate in Participants With Reflux Esophagitis | Up to 8 weeks | Endoscopic cure rate was defined as a percentage of participants who treated for reflux esophagitis and met the criteria of Grade N or M in the modified Los Angeles (LA) classification at the end of survey. Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the survey at 291 investigative sites in Japan, from 01 March 2016 to 31 October 2018.
Pre-assignment details
Participants with a historical diagnosis of gastric ulcer, duodenal ulcer, and reflux esophagitis were enrolled. Participants received vonoprazan as part of a routine medical care.
Participants by arm
| Arm | Count |
|---|---|
| Vonoprazan 20 mg The usual adult dosage for oral use is 20 mg of vonoprazan administered orally once daily. An 8-week treatment for gastric ulcer and a 6-week treatment for duodenal ulcer. For reflux esophagitis, the usual adult dosage for oral use was administered for a total of 4 weeks of treatment, and if that dosing proved insufficient, the administration may have been extended, but for no longer than 8 weeks of treatment. Participants received vonoprazan as part of a routine medical care. | 3,125 |
| Total | 3,125 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case Report Forms Uncollected | 13 |
| Overall Study | Protocol Deviation | 45 |
Baseline characteristics
| Characteristic | Vonoprazan 20 mg | — |
|---|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 16.42 | — |
| BMI | 23.15 Kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 3.798 | — |
| Drinking Habits No | 1704 Participants | — |
| Drinking Habits Unknown | 637 Participants | — |
| Drinking Habits Yes | 784 Participants | — |
| Duration of Diagnosis of Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis | 38.3 Days STANDARD_DEVIATION 281.47 | — |
| Duration of Prior Treatment < 1 month | 436 Participants | — |
| Duration of Prior Treatment >= 1 month and < 2 months | 56 Participants | — |
| Duration of Prior Treatment >= 2 months | 299 Participants | — |
| Endoscopic Findings; Duodenal Ulcer Active stage, A1 and A2 | 370 Participants | — |
| Endoscopic Findings; Duodenal Ulcer Healing stage, H1 and H2 | 165 Participants | — |
| Endoscopic Findings; Gastric Ulcer Active stage, A1 and A2 | 784 Participants | — |
| Endoscopic Findings; Gastric Ulcer Healing stage, H1 and H2 | 247 Participants | — |
| Endoscopic Findings; Reflux Esophagitis Grade A | 626 Participants | — |
| Endoscopic Findings; Reflux Esophagitis Grade B | 389 Participants | — |
| Endoscopic Findings; Reflux Esophagitis Grade C | 171 Participants | — |
| Endoscopic Findings; Reflux Esophagitis Grade D | 90 Participants | — |
| Healthcare Category Inpatient | 381 Participants | — |
| Healthcare Category Outpatient | 2744 Participants | — |
| Height | 161.01 Centimeters (cm) STANDARD_DEVIATION 10.142 | — |
| Helicobacter Pylori Infection Negative | 1492 Participants | — |
| Helicobacter Pylori Infection Positive | 862 Participants | — |
| Helicobacter Pylori Infection Unknown | 771 Participants | — |
| Medical Complications Had Medical Complications | 1473 Participants | — |
| Medical Complications Had No Medical Complications | 1652 Participants | — |
| Medical History of Esophageal Hiatal Hernia Had Esophageal Hiatal Hernia | 1034 Participants | — |
| Medical History of Esophageal Hiatal Hernia Had No Esophageal Hiatal Hernia | 1920 Participants | — |
| Medical History of Esophageal Hiatal Hernia Unknown | 171 Participants | — |
| Medical History of Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Had Medical History | 590 Participants | — |
| Medical History of Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Had No Medical History | 2256 Participants | — |
| Medical History of Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Unknown | 279 Participants | — |
| Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity | 2893 Participants | — |
| Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity | 117 Participants | — |
| Predisposition to Hypersensitivity Unknown | 115 Participants | — |
| Prior Treatment for Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Had No Prior Treatment | 2280 Participants | — |
| Prior Treatment for Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Had Prior Treatment | 791 Participants | — |
| Prior Treatment for Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis Unknown | 54 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Japan | 3125 Participants | — |
| Sex: Female, Male Female | 1375 Participants | — |
| Sex: Female, Male Male | 1750 Participants | — |
| Smoking Classification Current Smoker | 626 Participants | — |
| Smoking Classification Ex-Smoker | 429 Participants | — |
| Smoking Classification Never Smoked | 1258 Participants | — |
| Smoking Classification Unknown | 812 Participants | — |
| Target Conditions of Study Treatment Duodenal Ulcer | 578 Participants | — |
| Target Conditions of Study Treatment Gastric Ulcer | 1097 Participants | — |
| Target Conditions of Study Treatment Reflux Esophagitis | 1540 Participants | — |
| Weight | 60.46 Kilograms (kg) STANDARD_DEVIATION 13.377 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 3,125 |
| other Total, other adverse events | 10 / 3,125 |
| serious Total, serious adverse events | 20 / 3,125 |
Outcome results
Primary
Percentage of Participants With Duodenal Ulcer Who Had One or More Adverse Drug Reactions
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug.
Time frame: Up to 6 weeks
Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey. Participants who treated for duodenal ulcer within the Safety Analysis Set were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Who Had One or More Adverse Drug Reactions | 1.21 Percentage of Participants |
Primary
Percentage of Participants With Gastric Ulcer Who Had One or More Adverse Drug Reactions
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug.
Time frame: Up to 8 weeks
Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey. Participants who treated for gastric ulcer within the Safety Analysis Set were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Who Had One or More Adverse Drug Reactions | 1.00 Percentage of Participants |
Primary
Percentage of Participants With Reflux Esophagitis Who Had One or More Adverse Drug Reactions
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction refers to AE related to the administered drug.
Time frame: Up to 8 weeks
Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey. Participants who treated for reflux esophagitis within the Safety Analysis Set were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Who Had One or More Adverse Drug Reactions | 0.78 Percentage of Participants |
Secondary
Endoscopic Cure Rate in Participants With Duodenal Ulcer
Endoscopic cure rate was defined as a percentage of participants treated for duodenal ulcer who classified as Scarring stage at the end of survey per Sakita-Miwa Classification. Endoscopic findings of ulcer were classified per Sakita-Miwa Classification as follows; Active stage: A1 and A2, Healing stage: H1 and H2, Scarring stage: S1 and S2.
Time frame: Up to 6 weeks
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for duodenal ulcer within Efficacy assessment population and evaluable for endoscopic cure rate were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Endoscopic Cure Rate in Participants With Duodenal Ulcer | 88.46 Percentage of Participants |
Secondary
Endoscopic Cure Rate in Participants With Gastric Ulcer
Endoscopic cure rate was defined as a percentage of participants treated for gastric ulcer who classified as Scarring stage at the end of survey per Sakita-Miwa Classification. Endoscopic findings of ulcer were classified per Sakita-Miwa Classification as follows; Active stage: A1 and A2, Healing stage: H1 and H2, Scarring stage: S1 and S2.
Time frame: Up to 8 weeks
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for gastric ulcer within Efficacy assessment population and evaluable for endoscopic cure rate were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Endoscopic Cure Rate in Participants With Gastric Ulcer | 78.72 Percentage of Participants |
Secondary
Endoscopic Cure Rate in Participants With Reflux Esophagitis
Endoscopic cure rate was defined as a percentage of participants who treated for reflux esophagitis and met the criteria of Grade N or M in the modified Los Angeles (LA) classification at the end of survey. Grade N: normal mucosa; Grade M: minimal changes to the mucosa, such as erythema and/or whitish turbidity.
Time frame: Up to 8 weeks
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for reflux esophagitis within Efficacy assessment population and evaluable for endoscopic cure rate were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Endoscopic Cure Rate in Participants With Reflux Esophagitis | 65.04 Percentage of Participants |
Secondary
Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved
Percentage of participants who treated for duodenal ulcer and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved.
Time frame: Baseline and at the end of the survey (up to 6 weeks)
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for duodenal ulcer within Efficacy assessment population and evaluable for subjective symptoms were analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Heartburn | 96.94 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Acid Reflux | 97.22 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Postprandial Fullness | 95.65 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Early Satiation | 98.78 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Epigastric Pain | 98.58 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Epigastric Burning | 100.00 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Abdominal Bloating | 93.81 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Nausea/Vomiting | 96.92 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Belching | 93.55 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Duodenal Ulcer Whose Subjective Symptoms Improved | Anorexia | 99.30 Percentage of Participants |
Secondary
Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved
Percentage of participants who treated for gastric ulcer and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved.
Time frame: Baseline and at the end of the survey (up to 8 weeks)
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for gastric ulcer within Efficacy assessment population and evaluable for subjective symptoms were analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Heartburn | 96.68 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Acid Reflux | 96.86 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Postprandial Fullness | 96.09 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Early Satiation | 97.08 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Epigastric Pain | 98.78 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Epigastric Burning | 97.62 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Abdominal Bloating | 95.65 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Nausea/Vomiting | 97.52 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Belching | 91.67 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Gastric Ulcer Whose Subjective Symptoms Improved | Anorexia | 98.22 Percentage of Participants |
Secondary
Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved
Percentage of participants who treated for reflux esophagitis and whose subjective symptoms, including heartburn, acid reflux, postprandial fullness, early satiation, epigastric pain, epigastric burning, abdominal bloating, nausea/vomiting, belching and anorexia, were improved was reported. Presence or absence and severity of subjective symptoms were graded as asymptomatic, mild (occasionally or slightly symptomatic), moderate (considerably symptomatic), and severe (unendurably symptomatic). Participants with whose subjective symptom was improved by one grade or better were defined as Improved.
Time frame: Baseline and at the end of the survey (up to 8 weeks)
Population: Efficacy assessment population, participants who completed the survey and evaluable for efficacy; Participants who treated for reflux esophagitis within Efficacy assessment population and evaluable for subjective symptoms were analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Heartburn | 96.20 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Acid Reflux | 94.33 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Postprandial Fullness | 93.22 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Early Satiation | 92.37 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Epigastric Pain | 95.79 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Epigastric Burning | 96.72 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Abdominal Bloating | 90.04 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Nausea/Vomiting | 95.47 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Belching | 89.38 Percentage of Participants |
| Vonoprazan 20 mg | Percentage of Participants With Reflux Esophagitis Whose Subjective Symptoms Improved | Anorexia | 93.96 Percentage of Participants |