Erosive Esophagitis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of the study is to demonstrate the efficacy of vonoprazan (TAK-438) versus lansoprazole in the treatment of erosive esophagitis classified as Los Angeles (LA) classification grades A to D at Week 8.
Detailed description
The drug being tested in this study is called vonoprazan. Vonoprazan is being tested to treat people who have erosive esophagitis. This study will look at mucosal healing of people who take vonoprazan versus lansoprazole. This study will enroll approximately 480 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Vonoprazan 20 mg * Lansoprazole 30 mg All participants will be asked to take one tablet and one capsule at the same time each day throughout the study. All participants will be asked to record daytime and nighttime (during sleep) subjective symptoms in a diary on a daily basis. This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 11 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 7-14 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGVonoprazan
Vonoprazan tablets
DRUGLansoprazole
Lansoprazole capsules
Vonoprazan placebo-matching tablets
Lansoprazole placebo-matching capsules
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Has been confirmed in an endoscopy to have erosive esophagitis, ie, the Los Angeles (LA) classification grades A to D within 7 days of the start of the Day 1 (Visit 2). Note: The recruitment goal is to ensure that those with LA classification grade C/D will account for more than 30% of all participants enrolled (144/480), with no further recruitment of those with grade A/B considered when they account for more than 70% (336/480) of all participants. 4. Is aged 18 years old or older (or the local age of consent if that is older), male or female, at the time of signing an informed consent, and is being treated on an outpatient basis for erosive esophagitis, including those admitted temporarily for examination. 5. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
Exclusion criteria
1. Has received any investigational compound within 84 days prior to the start of the Observation phase. 2. Has received TAK-438 in a previous clinical study or as a therapeutic agent. 3. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening. 5. Has a history or clinical manifestations of serious central nerve system (CNS), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine or hematological disease. 6. Has a history of hypersensitivity or allergies to TAK-438 (including its excipients\*) or to proton pump inhibitors (PPIs). \*D-mannitol, crystalline cellulose, hydroxypropyl cellulose, fumaric acid, croscarmellose sodium, magnesium stearate, hypromellose, macrogol 6000, titanium oxide, yellow iron sesquioxide and iron sesquioxide. 7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Observation Phase (Visit 1). 8. Is required to take excluded medications. 9. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. 10. Has participated in another clinical study within the past 30 days from Visit 1. 11. Has co-morbidities that could affect the esophagus (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal strictures), a history of radiotherapy or cryotherapy for the esophagus; those with corrosive or physiochemical injury (with the possible inclusion in the study of those with Schatzki's ring or Barrett's esophagus). 12. Has a history of surgical procedures that may affect the esophagus (eg, fundoplication and mechanical dilatation for esophageal strictures excluding Schatzki's ring) or a history of gastric or duodenal surgery excluding endoscopic removal of benign polyps. 13. Developed acute upper gastrointestinal bleeding, gastric ulcer (a mucosal defect with white coating) or duodenal ulcer (a mucosal defect with white coating), within 30 days before the start of the Observation Phase (Visit 1) (with the possible inclusion of those with gastric or duodenal erosion). 14. Has Zollinger-Ellison syndrome or gastric acid hypersecretion or a history of gastric acid hypersecretion. 15. Is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study. 16. Has a history of malignancy or was treated for malignancy within 5 years before the start of the Observation Phase (Visit 1) (the participant may be included in the study if he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ). 17. Has acquired immunodeficiency syndrome (AIDS) or hepatitis, including hepatitis virus carriers: hepatitis B surface antigen (HBsAg) positive, or hepatitis C virus (HCV)-antibody-positive (the participant may be included in the study if he/she is HCV-antigen or HCV-ribonucleic acid \[RNA\]-negative). 18. Laboratory tests performed at the start of the Early Observation Phase (visit 1) revealed any of the following abnormalities in the participant: 1. Creatinine levels: \>2 mg/dL (\>177 μmol/L). 2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total bilirubin levels: \> upper limit of normal (ULN). 19. Is active in the Screening Period after the closure of enrollment identified by the Sponsor or the number of participants randomized with LA classification A/B or C/D have reached the required sample size.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase | 8 weeks | Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) | On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. |
| Number of Participants With Markedly Abnormal Clinical Laboratory Findings | From Day 1 to 14 days after the last dose of study medication (up to 10 weeks) | Clinical Laboratory Safety tests included Chemistry, Hematology and Urinalysis. Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl transferase, CPK = creatine phosphokinase, BUN = blood urea nitrogen, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit, g/L = grams per liter, U/L = units per liter, mmol/L = millimoles per liter, pmol/L = picomoles per liter. |
| Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | From Day 1 to 14 days after the last dose of study medication (up to 10 weeks) | Number of participants with any markedly abnormal 12-lead ECG findings is reported. bpm = beats per minute, msec = milliseconds, CHG= change from baseline. |
| Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment | Week 2 and Week 4 | Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa. |
| Change From Baseline in Serum Gastrin | Baseline and Weeks 2, 4, and 8 | The change between the serum gastrin values collected at Weeks 2, 4, and 8 relative to baseline. |
| Change From Baseline in Serum Pepsinogen I | Baseline and Weeks 2, 4, and 8 | The change between the serum pepsinogen I values collected at Weeks 2, 4, and 8 relative to baseline. |
| Change From Baseline in Serum Pepsinogen II | Baseline and Weeks 2, 4, and 8 | The change between the serum pepsinogen II values collected at Weeks 2, 4, and 8 relative to baseline. |
| Number of Participants With Markedly Abnormal Vital Sign Measurements | From Day 1 to 14 days after the last dose of study medication (up to 10 weeks) | Number of participants with any markedly abnormal vital signs measurements is reported. Vital signs included body temperature (oral, tympanic, or infra-axillary measurement), sitting blood pressure (5 minutes), and pulse. °C = degrees Celsius, mmHg = millimeters of mercury, bpm = beats per minute. |
Countries
China, Malaysia, South Korea, Taiwan
Participant flow
Recruitment details
Participants took part in the study at 56 investigative sites in China, Korea, Taiwan, and Malaysia from 24 March 2015 to 27 July 2017.
Pre-assignment details
Participants with a diagnosis of erosive esophagitis were enrolled in a 1:1 ratio in one of two treatment groups, TAK-438 20 mg once daily (QD) or lansoprazole 30 mg QD.
Participants by arm
| Arm | Count |
|---|---|
| Vonoprazan 20 mg Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. | 244 |
| Lansoprazole 30 mg Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks. | 237 |
| Total | 481 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Major Protocol Deviation | 3 | 3 |
| Overall Study | Pretreatment Event/Adverse Event | 3 | 2 |
| Overall Study | Randomized but not Treated | 0 | 2 |
| Overall Study | Reason not Specified | 0 | 1 |
| Overall Study | Voluntary Withdrawal | 6 | 5 |
Baseline characteristics
| Characteristic | Total | Vonoprazan 20 mg | Lansoprazole 30 mg |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 12.84 | 54.1 years STANDARD_DEVIATION 13.16 | 53.8 years STANDARD_DEVIATION 12.53 |
| Barrett's Mucosa Absent | 428 Participants | 216 Participants | 212 Participants |
| Barrett's Mucosa Present (3 cm or Greater) | 14 Participants | 7 Participants | 7 Participants |
| Barrett's Mucosa Present (Less than 3 cm) | 25 Participants | 15 Participants | 10 Participants |
| Barrett's Mucosa Unknown | 12 Participants | 6 Participants | 6 Participants |
| Body Mass Index (BMI) | 25.00 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.419 | 24.70 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.389 | 25.31 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.43 |
| Consumption of Alcohol Drink a Couple of Days Per Month | 105 Participants | 57 Participants | 48 Participants |
| Consumption of Alcohol Drink a Couple of Days Per Week | 72 Participants | 32 Participants | 40 Participants |
| Consumption of Alcohol Drink Everyday | 25 Participants | 13 Participants | 12 Participants |
| Consumption of Alcohol Never Drink | 279 Participants | 142 Participants | 137 Participants |
| Consumption of Caffeine No | 370 Participants | 185 Participants | 185 Participants |
| Consumption of Caffeine Yes | 110 Participants | 58 Participants | 52 Participants |
| Diary for Gastrointestinal Symptoms: Mean Severity of Heartburn Symptoms | 0.782 score on a scale STANDARD_DEVIATION 0.6792 | 0.797 score on a scale STANDARD_DEVIATION 0.7153 | 0.767 score on a scale STANDARD_DEVIATION 0.6408 |
| Esophageal Hiatal Hernia Absent | 346 Participants | 180 Participants | 166 Participants |
| Esophageal Hiatal Hernia Present (2 cm or Greater) | 75 Participants | 36 Participants | 39 Participants |
| Esophageal Hiatal Hernia Present (Less than 2 cm) | 48 Participants | 24 Participants | 24 Participants |
| Esophageal Hiatal Hernia Unknown | 10 Participants | 4 Participants | 6 Participants |
| EuroQol-visual analogue scales (EQ VAS) Score | 85.4 score on a scale STANDARD_DEVIATION 11.21 | 85.7 score on a scale STANDARD_DEVIATION 10.88 | 85.2 score on a scale STANDARD_DEVIATION 11.56 |
| Health-Related Quality of Life (HRQoL) EQ-5D-5L Index Value | 0.9495 score on a scale STANDARD_DEVIATION 0.06885 | 0.9503 score on a scale STANDARD_DEVIATION 0.07278 | 0.9486 score on a scale STANDARD_DEVIATION 0.06466 |
| Height | 166.2 centimeters (cm) STANDARD_DEVIATION 8.52 | 166.1 centimeters (cm) STANDARD_DEVIATION 8.24 | 166.3 centimeters (cm) STANDARD_DEVIATION 8.8 |
| History of H. pylori Eradication Therapy No | 431 Participants | 220 Participants | 211 Participants |
| History of H. pylori Eradication Therapy Yes (End of Treatment: More than 1 Year) | 40 Participants | 18 Participants | 22 Participants |
| History of H. pylori Eradication Therapy Yes (End of Treatment: Within the Past 1 Year) | 10 Participants | 6 Participants | 4 Participants |
| H. pylori Infection Status Negative | 401 Participants | 205 Participants | 196 Participants |
| H. pylori Infection Status Positive | 74 Participants | 36 Participants | 38 Participants |
| LA Classification for Diagnosis and Grading of Erosive Esophagitis Grade A | 159 Participants | 76 Participants | 83 Participants |
| LA Classification for Diagnosis and Grading of Erosive Esophagitis Grade B | 176 Participants | 92 Participants | 84 Participants |
| LA Classification for Diagnosis and Grading of Erosive Esophagitis Grade C | 116 Participants | 58 Participants | 58 Participants |
| LA Classification for Diagnosis and Grading of Erosive Esophagitis Grade D | 28 Participants | 18 Participants | 10 Participants |
| LA Classification for Diagnosis and Grading of Erosive Esophagitis Grade O | 0 Participants | 0 Participants | 0 Participants |
| Mean Severity of Gastric Acid Regurgitation | 0.750 score on a scale STANDARD_DEVIATION 0.6745 | 0.772 score on a scale STANDARD_DEVIATION 0.6765 | 0.727 score on a scale STANDARD_DEVIATION 0.6731 |
| Race/Ethnicity, Customized Asian | 481 Participants | 244 Participants | 237 Participants |
| Region of Enrollment Asia China | 276 Participants | 143 Participants | 133 Participants |
| Region of Enrollment Asia Malaysia | 45 Participants | 21 Participants | 24 Participants |
| Region of Enrollment Asia South Korea | 107 Participants | 52 Participants | 55 Participants |
| Region of Enrollment Asia Taiwan | 53 Participants | 28 Participants | 25 Participants |
| Sex: Female, Male Female | 126 Participants | 68 Participants | 58 Participants |
| Sex: Female, Male Male | 355 Participants | 176 Participants | 179 Participants |
| Smoking Classification Current Smoker | 112 Participants | 48 Participants | 64 Participants |
| Smoking Classification Ex-Smoker | 75 Participants | 39 Participants | 36 Participants |
| Smoking Classification Never Smoked | 294 Participants | 157 Participants | 137 Participants |
| Weight | 69.35 kilograms (kg) STANDARD_DEVIATION 12.243 | 68.48 kilograms (kg) STANDARD_DEVIATION 12.311 | 70.26 kilograms (kg) STANDARD_DEVIATION 12.133 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 244 | 0 / 235 |
| other Total, other adverse events | 13 / 244 | 4 / 235 |
| serious Total, serious adverse events | 3 / 244 | 3 / 235 |
Outcome results
Primary
Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase
Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa.
Time frame: 8 weeks
Population: The full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline endoscopy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase | 92.4 percentage of participants |
| Lansoprazole 30 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase | 91.3 percentage of participants |
95% CI: [-3.822, 6.087]
Secondary
Change From Baseline in Serum Gastrin
The change between the serum gastrin values collected at Weeks 2, 4, and 8 relative to baseline.
Time frame: Baseline and Weeks 2, 4, and 8
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vonoprazan 20 mg | Change From Baseline in Serum Gastrin | Baseline | 2.77 pmol/L | Standard Deviation 4.084 |
| Vonoprazan 20 mg | Change From Baseline in Serum Gastrin | Change at Week 2 | 31.45 pmol/L | Standard Deviation 28.995 |
| Vonoprazan 20 mg | Change From Baseline in Serum Gastrin | Change at Week 4 | 29.68 pmol/L | Standard Deviation 29.189 |
| Vonoprazan 20 mg | Change From Baseline in Serum Gastrin | Change at Week 8 | 36.53 pmol/L | Standard Deviation 37.108 |
| Lansoprazole 30 mg | Change From Baseline in Serum Gastrin | Change at Week 8 | 4.71 pmol/L | Standard Deviation 7.727 |
| Lansoprazole 30 mg | Change From Baseline in Serum Gastrin | Baseline | 3.65 pmol/L | Standard Deviation 8.622 |
| Lansoprazole 30 mg | Change From Baseline in Serum Gastrin | Change at Week 4 | 6.81 pmol/L | Standard Deviation 9.969 |
| Lansoprazole 30 mg | Change From Baseline in Serum Gastrin | Change at Week 2 | 8.33 pmol/L | Standard Deviation 10.19 |
Secondary
Change From Baseline in Serum Pepsinogen I
The change between the serum pepsinogen I values collected at Weeks 2, 4, and 8 relative to baseline.
Time frame: Baseline and Weeks 2, 4, and 8
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen I | Baseline | 97.6 micrograms per liter (ug/L) | Standard Deviation 53.54 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 2 | 456.5 micrograms per liter (ug/L) | Standard Deviation 308.22 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 4 | 421.8 micrograms per liter (ug/L) | Standard Deviation 324.06 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 8 | 326.8 micrograms per liter (ug/L) | Standard Deviation 233.8 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 8 | 117.8 micrograms per liter (ug/L) | Standard Deviation 98.03 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen I | Baseline | 99.8 micrograms per liter (ug/L) | Standard Deviation 61.99 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 4 | 118.3 micrograms per liter (ug/L) | Standard Deviation 113.24 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen I | Change at Week 2 | 129.3 micrograms per liter (ug/L) | Standard Deviation 138.24 |
Secondary
Change From Baseline in Serum Pepsinogen II
The change between the serum pepsinogen II values collected at Weeks 2, 4, and 8 relative to baseline.
Time frame: Baseline and Weeks 2, 4, and 8
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 8 | 31.0 ug/L | Standard Deviation 20.03 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 2 | 44.9 ug/L | Standard Deviation 31.31 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen II | Baseline | 7.5 ug/L | Standard Deviation 5.5 |
| Vonoprazan 20 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 4 | 40.7 ug/L | Standard Deviation 26.1 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen II | Baseline | 7.8 ug/L | Standard Deviation 5.77 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 8 | 8.0 ug/L | Standard Deviation 8.46 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 4 | 7.2 ug/L | Standard Deviation 5.99 |
| Lansoprazole 30 mg | Change From Baseline in Serum Pepsinogen II | Change at Week 2 | 8.8 ug/L | Standard Deviation 9.63 |
Secondary
Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug.
Time frame: On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks)
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vonoprazan 20 mg | Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) | 93 Participants |
| Lansoprazole 30 mg | Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) | 86 Participants |
Secondary
Number of Participants With Markedly Abnormal Clinical Laboratory Findings
Clinical Laboratory Safety tests included Chemistry, Hematology and Urinalysis. Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl transferase, CPK = creatine phosphokinase, BUN = blood urea nitrogen, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit, g/L = grams per liter, U/L = units per liter, mmol/L = millimoles per liter, pmol/L = picomoles per liter.
Time frame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Eosinophils (>2 x ULN %) | 1 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | CPK (>5 x ULN U/L) | 1 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | ALT (>3 x ULN U/L) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Total Protein (>1.2 x ULN g/L) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Neutrophils (<0.5 x LLN %) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | BUN (>10.7 mmol/L) | 1 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | AST (>3 x ULN U/L) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Total Cholesterol (>7.72 mmol/L) | 3 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Lymphocytes (>1.5 x ULN %) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Triglycerides (>2.5 x ULN mmol/L) | 6 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | GGT (>3 x ULN U/L) | 4 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Vitamin B12 (<92 pmol/L) | 0 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Hemoglobin (<0.8 x LLN g/L) | 0 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Vitamin B12 (<92 pmol/L) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Hemoglobin (<0.8 x LLN g/L) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Neutrophils (<0.5 x LLN %) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Eosinophils (>2 x ULN %) | 0 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Lymphocytes (>1.5 x ULN %) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | ALT (>3 x ULN U/L) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | AST (>3 x ULN U/L) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | GGT (>3 x ULN U/L) | 3 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | CPK (>5 x ULN U/L) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Total Protein (>1.2 x ULN g/L) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | BUN (>10.7 mmol/L) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Total Cholesterol (>7.72 mmol/L) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Clinical Laboratory Findings | Triglycerides (>2.5 x ULN mmol/L) | 3 Participants |
Secondary
Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
Number of participants with any markedly abnormal 12-lead ECG findings is reported. bpm = beats per minute, msec = milliseconds, CHG= change from baseline.
Time frame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | Heart Rate (<50 bpm) | 6 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | QT Interval (≥460 msec) | 7 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | QTcF Interval (≥500, or ≥450 with CHG ≥30 msec) | 3 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | Heart Rate (<50 bpm) | 7 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | QT Interval (≥460 msec) | 10 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | QTcF Interval (≥500, or ≥450 with CHG ≥30 msec) | 5 Participants |
Secondary
Number of Participants With Markedly Abnormal Vital Sign Measurements
Number of participants with any markedly abnormal vital signs measurements is reported. Vital signs included body temperature (oral, tympanic, or infra-axillary measurement), sitting blood pressure (5 minutes), and pulse. °C = degrees Celsius, mmHg = millimeters of mercury, bpm = beats per minute.
Time frame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Population: The safety analysis set (SAF) included all participants who took at least 1 dose of study medication. The number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Body Temperature (>37.7 °C) | 2 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic Blood Pressure (>110 mmHg) | 1 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Systolic Blood Pressure (<85 mmHg) | 1 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (<50 bpm) | 2 Participants |
| Vonoprazan 20 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Body Temperature (<35.6 °C) | 10 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (<50 bpm) | 2 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Body Temperature (<35.6 °C) | 3 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Body Temperature (>37.7 °C) | 0 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Systolic Blood Pressure (<85 mmHg) | 1 Participants |
| Lansoprazole 30 mg | Number of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic Blood Pressure (>110 mmHg) | 0 Participants |
Secondary
Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment
Endoscopic healing is defined as participants endoscopically diagnosed as Los Angeles classification grade O during the treatment phase. Grade O indicates there are no mucosal breaks in the mucosa.
Time frame: Week 2 and Week 4
Population: The full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline endoscopy. Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vonoprazan 20 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment | 2 Weeks | 75.0 percentage of participants |
| Vonoprazan 20 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment | 4 Weeks | 85.3 percentage of participants |
| Lansoprazole 30 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment | 2 Weeks | 67.8 percentage of participants |
| Lansoprazole 30 mg | Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment | 4 Weeks | 83.5 percentage of participants |
Comparison: 2 Weeks95% CI: [-1.054, 15.371]
Comparison: 4 Weeks95% CI: [-4.763, 8.395]