Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Participants With Erosive Esophagitis

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02388724
• Collaborator: (none)
• Enrollment: 481
• Locations: 64
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Erosive Esophagitis	Drug: Vonoprazan; Drug: Lansoprazole; Drug: Vonoprazan Placebo; Drug: Lansoprazole Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 481 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Double-Dummy Phase 3 Study to Evaluate the Efficacy and Safety of Oral Once-Daily Administration of TAK-438 20 mg Compared to Lansoprazole 30 mg in the Treatment of Subjects With Erosive Esophagitis
• Actual Study Start Date: Mar 24, 2015
• Actual Primary Completion Date: Jul 27, 2017
• Actual Study Completion Date: Jul 27, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vonoprazan 20 mg Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Drug: Vonoprazan; Vonoprazan tablets; Other Names: TAK-438 ; Drug: Lansoprazole Placebo; Lansoprazole placebo-matching capsules
Active Comparator: Lansoprazole 30 mg Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.	Drug: Lansoprazole; Lansoprazole capsules; Other Names: Prevacid ; Drug: Vonoprazan Placebo; Vonoprazan placebo-matching tablets

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

1. 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.

2. 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.

1. 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).

2. Is required to take excluded medications.

3. 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.

4. Has participated in another clinical study within the past 30 days from Visit 1.

5. 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).

6. 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.

7. 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).

8. Has Zollinger-Ellison syndrome or gastric acid hypersecretion or a history of gastric acid hypersecretion.

9. Is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study.

10. 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).

11. 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).

12. Laboratory tests performed at the start of the Early Observation Phase (visit 1) revealed any of the following abnormalities in the participant:

13. Creatinine levels: >2 mg/dL (>177 μmol/L).

14. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total bilirubin levels: > upper limit of normal (ULN).

15. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chao Yang Hospital	Beijing	Beijing	China	100020
2	China-Japan Friendship hospital	Beijing	Beijing	China	100029
3	Peking Union Medical College Hospital	Beijing	Beijing	China	100032
4	Beijing Tongren Hospital, Capital Medical Univeristy	Beijing	Beijing	China	100370
5	PLA.The Military General Hospital of Beijing	Beijing	Beijing	China	100700
6	Fuzhou General Hospital of Nanjing Military Command	Fuzhou	Fujian	China	350100
7	Guangdong General Hospital	Guangzhou	Guangdong	China	510080
8	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510080
9	Union Hospital of Tongji Medical College of Huazhong Science and Techology University	Wuhan	Hubei	China	430022
10	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Techology	Wuhan	Hubei	China	430030
11	The 2nd Xiangya Hospital Central South University	Changsha	Hunan	China	410011
12	Chenzhou No.1 People's Hospital	Chenzhou	Hunan	China	432000
13	The First People's Hospital of Changzhou	Changzhou City	Jiangsu	China	213003
14	Jiangsu Province People's Hospital	Nanjing	Jiangsu	China	210029
15	No.2 Hospital Affiliated to Jilin University	Changchun	Jilin	China	130041
16	Jilin central Hospital	Jilin	Jilin	China	132011
17	General Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750004
18	Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.	Shanghai	Shanghai	China	200025
19	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
20	TongJi Hospital of Tongji University	Shanghai	Shanghai	China	200065
21	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
22	The 2nd Hospital of Tianjin Medical University	Tianjin	Tianjin	China	300211
23	The First Affiated Hospital of Kunming Medical College	Kunming	Yunnan	China	650032
24	2nd Affiliated Hospital, Zhejiang Univ. School of Medicine	Hangzhou	Zhejiang	China	310009
25	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang	China	310016
26	Beijing Friendship Hospital, Capital Medical University	Beijing		China	100050
27		Beijing		China
28	The Second Affiliated Hospital of Chongqing Medical University	Chongqing		China	0
29	1st Affiliated Hospital of Zhejiang University	Hangzhou		China
30	The First Affiliated Hospital of NanChang University	Nanchang		China
31	The Affiliated DrumTower Hospital of Nanjing University	Nanjing		China	210008
32		Tianjin		China
33	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
34	Seoul National University Hospital	Seoul	Gyeonggi-do	Korea, Republic of	03080
35	Kyungpook National University Medical Center	Daegu	Gyeongsangbuk-do	Korea, Republic of	41404
36	Wonkwang University School Of Medicine & Hospital	Iksan-si	Jeollabuk-do	Korea, Republic of	54538
37	Pusan National University Hospital	Busan		Korea, Republic of	49241
38	Yeungnam University Hospital	Daegu		Korea, Republic of	42415
39	Kyung Hee University Hospital	Seoul		Korea, Republic of	02447
40	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
41	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
42	Asan Medical Center	Seoul		Korea, Republic of	05505
43	Samsung Medical Center	Seoul		Korea, Republic of	06351
44	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul		Korea, Republic of	06591
45	Hospital Sultana Bahiyah	Alor Setar	Kedah	Malaysia	5460
46	Hospital Raja Perempuan Zainab II	Kota Bahru	Kelantan	Malaysia	15586
47	Hospital Tengku Ampuan Afzan	Kuantan	Pahang	Malaysia	25100
48	Hospital Queen Elizabeth	Kota Kinabalu	Sabah	Malaysia	88586
49	Hospital Ampang	Ampang	Selangor	Malaysia	68000
50	Hospital Universiti Sains Malaysia	Kelantan		Malaysia	16150
51	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia	50586
52	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
53	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
54	E-Da Hospital	Kaohsiung		Taiwan	824
55	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	833
56	China Medical University Hospital	Taichung		Taiwan	333
57	Chung Shan Medical University Hospital	Taichung		Taiwan	402
58	Cheng Ching General Hospital-Chung Kang Branch	Taichung		Taiwan	407
59	National Cheng Kung University Hospital	Tainan		Taiwan	704
60	Taipei Medical University Hospital	Taipei City		Taiwan	110
61	National Taiwan University Hospital	Taipei		Taiwan	100
62	Taipei Veterans General Hospital	Taipei		Taiwan	112
63	Tri-Service General Hospital	Taipei		Taiwan	114
64	Chang Gung Memorial Hospital, Linkou	Taoyuan County		Taiwan	333

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 23, 2017
• Study Protocol - Sep 1, 2016

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02388724
• Other Study ID Numbers: TAK-438_303; U1111-1138-4788; CTR20150040
• First Posted: Mar 17, 2015
• Last Update Posted: Jun 3, 2019
• Last Verified: Feb 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Esophagitis; Lansoprazole; Dexlansoprazole

Study Results

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 Detail	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.

Arm/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Period Title: Overall Study
STARTED	244	237
Safety Set: Randomized But Not Treated	0	2
COMPLETED	232	224
NOT COMPLETED	12	13

Baseline Characteristics

Arm/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg	Total
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.	Total of all reporting groups
Overall Participants	244	237	481
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.1 (13.16)	53.8 (12.53)	53.9 (12.84)
Sex: Female, Male (Count of Participants)
Female	68 27.9%	58 24.5%	126 26.2%
Male	176 72.1%	179 75.5%	355 73.8%
Race/Ethnicity, Customized (Count of Participants)
Asian	244 100%	237 100%	481 100%
Region of Enrollment (Count of Participants)
China	143 58.6%	133 56.1%	276 57.4%
Malaysia	21 8.6%	24 10.1%	45 9.4%
South Korea	52 21.3%	55 23.2%	107 22.2%
Taiwan	28 11.5%	25 10.5%	53 11%
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	166.1 (8.24)	166.3 (8.80)	166.2 (8.52)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	68.48 (12.311)	70.26 (12.133)	69.35 (12.243)
Body Mass Index (BMI) (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per square meter (kg/m^2)]	24.70 (3.389)	25.31 (3.430)	25.00 (3.419)
Smoking Classification (Count of Participants)
Never Smoked	157 64.3%	137 57.8%	294 61.1%
Current Smoker	48 19.7%	64 27%	112 23.3%
Ex-Smoker	39 16%	36 15.2%	75 15.6%
Consumption of Alcohol (Count of Participants)
Drink Everyday	13 5.3%	12 5.1%	25 5.2%
Drink a Couple of Days Per Week	32 13.1%	40 16.9%	72 15%
Drink a Couple of Days Per Month	57 23.4%	48 20.3%	105 21.8%
Never Drink	142 58.2%	137 57.8%	279 58%
Consumption of Caffeine (Count of Participants)
Yes	58 23.8%	52 21.9%	110 22.9%
No	185 75.8%	185 78.1%	370 76.9%
History of H. pylori Eradication Therapy (Count of Participants)
Yes (End of Treatment: Within the Past 1 Year)	6 2.5%	4 1.7%	10 2.1%
Yes (End of Treatment: More than 1 Year)	18 7.4%	22 9.3%	40 8.3%
No	220 90.2%	211 89%	431 89.6%
H. pylori Infection Status (Count of Participants)
Positive	36 14.8%	38 16%	74 15.4%
Negative	205 84%	196 82.7%	401 83.4%
LA Classification for Diagnosis and Grading of Erosive Esophagitis (Count of Participants)
Grade O	0 0%	0 0%	0 0%
Grade A	76 31.1%	83 35%	159 33.1%
Grade B	92 37.7%	84 35.4%	176 36.6%
Grade C	58 23.8%	58 24.5%	116 24.1%
Grade D	18 7.4%	10 4.2%	28 5.8%
Barrett's Mucosa (Count of Participants)
Present (3 cm or Greater)	7 2.9%	7 3%	14 2.9%
Present (Less than 3 cm)	15 6.1%	10 4.2%	25 5.2%
Absent	216 88.5%	212 89.5%	428 89%
Unknown	6 2.5%	6 2.5%	12 2.5%
Esophageal Hiatal Hernia (Count of Participants)
Present (2 cm or Greater)	36 14.8%	39 16.5%	75 15.6%
Present (Less than 2 cm)	24 9.8%	24 10.1%	48 10%
Absent	180 73.8%	166 70%	346 71.9%
Unknown	4 1.6%	6 2.5%	10 2.1%
Diary for Gastrointestinal Symptoms: Mean Severity of Heartburn Symptoms (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	0.797 (0.7153)	0.767 (0.6408)	0.782 (0.6792)
Mean Severity of Gastric Acid Regurgitation (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	0.772 (0.6765)	0.727 (0.6731)	0.750 (0.6745)
Health-Related Quality of Life (HRQoL) EQ-5D-5L Index Value (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	0.9503 (0.07278)	0.9486 (0.06466)	0.9495 (0.06885)
EuroQol-visual analogue scales (EQ VAS) Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	85.7 (10.88)	85.2 (11.56)	85.4 (11.21)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	238	230
Number (95% Confidence Interval) [percentage of participants]	92.4 37.9%	91.3 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonoprazan 20 mg, Lansoprazole 30 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% confidence intervals of the difference was more than -10% (non-inferiority margin), non-inferiority for Vonoprazan relative to Lansoprazole was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -3.822 to 6.087
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	238	230
2 Weeks	75.0 30.7%	67.8 28.6%
4 Weeks	85.3 35%	83.5 35.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonoprazan 20 mg, Lansoprazole 30 mg
	Comments	2 Weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 95%; -1.054 to 15.371
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vonoprazan 20 mg, Lansoprazole 30 mg
	Comments	4 Weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -4.763 to 8.395
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)
Description	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)

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) included all participants who took at least 1 dose of study medication.

Arm/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Count of Participants [Participants]	93 38.1%	86 36.3%

4. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Clinical Laboratory Findings
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Hemoglobin (<0.8 x LLN g/L)	0 0%	1 0.4%
Neutrophils (<0.5 x LLN %)	0 0%	2 0.8%
Eosinophils (>2 x ULN %)	1 0.4%	0 0%
Lymphocytes (>1.5 x ULN %)	0 0%	2 0.8%
ALT (>3 x ULN U/L)	0 0%	2 0.8%
AST (>3 x ULN U/L)	0 0%	1 0.4%
GGT (>3 x ULN U/L)	4 1.6%	3 1.3%
CPK (>5 x ULN U/L)	1 0.4%	2 0.8%
Total Protein (>1.2 x ULN g/L)	0 0%	1 0.4%
BUN (>10.7 mmol/L)	1 0.4%	1 0.4%
Total Cholesterol (>7.72 mmol/L)	3 1.2%	2 0.8%
Triglycerides (>2.5 x ULN mmol/L)	6 2.5%	3 1.3%
Vitamin B12 (<92 pmol/L)	0 0%	1 0.4%

5. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Heart Rate (<50 bpm)	6 2.5%	7 3%
QT Interval (≥460 msec)	7 2.9%	10 4.2%
QTcF Interval (≥500, or ≥450 with CHG ≥30 msec)	3 1.2%	5 2.1%

6. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Vital Sign Measurements
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Body Temperature (<35.6 °C)	10 4.1%	3 1.3%
Body Temperature (>37.7 °C)	2 0.8%	0 0%
Systolic Blood Pressure (<85 mmHg)	1 0.4%	1 0.4%
Diastolic Blood Pressure (>110 mmHg)	1 0.4%	0 0%
Pulse (<50 bpm)	2 0.8%	2 0.8%

7. Secondary Outcome

Title	Change From Baseline in Serum Gastrin
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Baseline	2.77 (4.084)	3.65 (8.622)
Change at Week 2	31.45 (28.995)	8.33 (10.190)
Change at Week 4	29.68 (29.189)	6.81 (9.969)
Change at Week 8	36.53 (37.108)	4.71 (7.727)

8. Secondary Outcome

Title	Change From Baseline in Serum Pepsinogen I
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Baseline	97.6 (53.54)	99.8 (61.99)
Change at Week 2	456.5 (308.22)	129.3 (138.24)
Change at Week 4	421.8 (324.06)	118.3 (113.24)
Change at Week 8	326.8 (233.80)	117.8 (98.03)

9. Secondary Outcome

Title	Change From Baseline in Serum Pepsinogen II
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Vonoprazan 20 mg	Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.	Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
Measure Participants	244	235
Baseline	7.5 (5.50)	7.8 (5.77)
Change at Week 2	44.9 (31.31)	8.8 (9.63)
Change at Week 4	40.7 (26.10)	7.2 (5.99)
Change at Week 8	31.0 (20.03)	8.0 (8.46)

Adverse Events

Time Frame	Up to 10 weeks (8 weeks of treatment and 2 weeks of post-treatment follow-up period)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal physical examination and laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Vonoprazan 20 mg		Lansoprazole 30 mg
Arm/Group Description	Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks.		Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
All Cause Mortality
	Vonoprazan 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/244 (0%)		0/235 (0%)
Serious Adverse Events
	Vonoprazan 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/244 (1.2%)		3/235 (1.3%)
Eye disorders
Glaucoma	0/244 (0%)		1/235 (0.4%)
Gastrointestinal disorders
Large intestine polyp	0/244 (0%)		1/235 (0.4%)
Hepatobiliary disorders
Bile duct stone	1/244 (0.4%)		0/235 (0%)
Infections and infestations
Gastroenteritis	0/244 (0%)		1/235 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma	1/244 (0.4%)		0/235 (0%)
Nervous system disorders
Cerebral infarction	1/244 (0.4%)		0/235 (0%)
Other (Not Including Serious) Adverse Events
	Vonoprazan 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/244 (5.3%)		4/235 (1.7%)
Investigations
Blood gastrin increased	13/244 (5.3%)		4/235 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study-related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.