Clinical trial NCT02388724: Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Participants With Erosive Esophagitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Erosive Esophagitis
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase
timeFrame: 8 weeks
Secondary outcomes:
measure: Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment
timeFrame: Week 2 and Week 4
measure: Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)
timeFrame: On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks)
measure: Number of Participants With Markedly Abnormal Clinical Laboratory Findings
timeFrame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
measure: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
timeFrame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
measure: Number of Participants With Markedly Abnormal Vital Sign Measurements
timeFrame: From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
measure: Change From Baseline in Serum Gastrin
timeFrame: Baseline and Weeks 2, 4, and 8
measure: Change From Baseline in Serum Pepsinogen I
timeFrame: Baseline and Weeks 2, 4, and 8
measure: Change From Baseline in Serum Pepsinogen II
timeFrame: Baseline and Weeks 2, 4, and 8
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical Univeristy
state: Beijing
city: Beijing
country: China
facility: PLA.The Military General Hospital of Beijing
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Military Command
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College of Huazhong Science and Techology University
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Techology
state: Hubei
city: Changsha
country: China
facility: The 2nd Xiangya Hospital Central South University
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou No.1 People's Hospital
state: Hunan
city: Changzhou City
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province People's Hospital
state: Jiangsu
city: Changchun
country: China
facility: No.2 Hospital Affiliated to Jilin University
state: Jilin
city: Jilin
country: China
facility: Jilin central Hospital
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: TongJi Hospital of Tongji University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: The 2nd Hospital of Tianjin Medical University
state: Tianjin
city: Kunming
country: China
facility: The First Affiated Hospital of Kunming Medical College
state: Yunnan
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, Zhejiang Univ. School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
state: Zhejiang
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Hangzhou
country: China
facility: 1st Affiliated Hospital of Zhejiang University
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
city: Nanjing
country: China
facility: The Affiliated DrumTower Hospital of Nanjing University
city: Tianjin
country: China
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
state: Gyeongsangbuk-do
city: Iksan-si
country: Korea, Republic of
facility: Wonkwang University School Of Medicine & Hospital
state: Jeollabuk-do
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital
city: Alor Setar
country: Malaysia
facility: Hospital Sultana Bahiyah
state: Kedah
city: Kota Bahru
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
state: Kelantan
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
state: Sabah
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Selangor
city: Kelantan
country: Malaysia
facility: Hospital Universiti Sains Malaysia
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Cheng Ching General Hospital-Chung Kang Branch
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Xiao Y, Zhang S, Dai N, Fei G, Goh KL, Chun HJ, Sheu BS, Chong CF, Funao N, Zhou W, Chen M. Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis. Gut. 2020 Feb;69(2):224-230. doi: 10.1136/gutjnl-2019-318365. Epub 2019 Aug 13.