Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Participants With Erosive Esophagitis
- Conditions
- Erosive Esophagitis
- Interventions
- Registration Number
- NCT02388724
- Lead Sponsor
- Takeda
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 481
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In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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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.
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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.
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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.
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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.
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Has received any investigational compound within 84 days prior to the start of the Observation phase.
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Has received TAK-438 in a previous clinical study or as a therapeutic agent.
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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.
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Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening.
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Has a history or clinical manifestations of serious central nerve system (CNS), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine or hematological disease.
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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.
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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).
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Is required to take excluded medications.
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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.
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Has participated in another clinical study within the past 30 days from Visit 1.
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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).
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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.
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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).
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Has Zollinger-Ellison syndrome or gastric acid hypersecretion or a history of gastric acid hypersecretion.
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Is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study.
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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).
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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).
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Laboratory tests performed at the start of the Early Observation Phase (visit 1) revealed any of the following abnormalities in the participant:
- Creatinine levels: >2 mg/dL (>177 μmol/L).
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total bilirubin levels: > upper limit of normal (ULN).
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vonoprazan 20 mg Vonoprazan Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. Vonoprazan 20 mg Lansoprazole Placebo Vonoprazan 20 mg, tablet, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily for up to 8 weeks. Lansoprazole 30 mg Vonoprazan Placebo Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks. Lansoprazole 30 mg Lansoprazole Lansoprazole 30 mg, capsule, orally, once daily and vonoprazan placebo-matching tablet, orally, once daily for up to 8 weeks.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
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 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.
Trial Locations
- Locations (62)
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Beijing Tongren Hospital, Capital Medical Univeristy
🇨🇳Beijing, Beijing, China
Kyungpook National University Medical Center
🇰🇷Daegu, Gyeongsangbuk-do, Korea, Republic of
Wonkwang University School Of Medicine & Hospital
🇰🇷Iksan-si, Jeollabuk-do, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Sabah, Malaysia
Seoul National University Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Fuzhou General Hospital of Nanjing Military Command
🇨🇳Fuzhou, Fujian, China
The 2nd Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Beijing Chao Yang Hospital
🇨🇳Beijing, Beijing, China
China-Japan Friendship hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Techology
🇨🇳Wuhan, Hubei, China
Chenzhou No.1 People's Hospital
🇨🇳Chenzhou, Hunan, China
No.2 Hospital Affiliated to Jilin University
🇨🇳Changchun, Jilin, China
Jilin central Hospital
🇨🇳Jilin, Jilin, China
Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
The Second Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
1st Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China
The First Affiliated Hospital of NanChang University
🇨🇳Nanchang, China
The Affiliated DrumTower Hospital of Nanjing University
🇨🇳Nanjing, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
PLA.The Military General Hospital of Beijing
🇨🇳Beijing, Beijing, China
Union Hospital of Tongji Medical College of Huazhong Science and Techology University
🇨🇳Wuhan, Hubei, China
Jiangsu Province People's Hospital
🇨🇳Nanjing, Jiangsu, China
The First People's Hospital of Changzhou
🇨🇳Changzhou City, Jiangsu, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
The 2nd Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
The First Affiated Hospital of Kunming Medical College
🇨🇳Kunming, Yunnan, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Taipei Medical University Hospital
🇨🇳Taipei City, Taiwan
Hospital Raja Perempuan Zainab II
🇲🇾Kota Bahru, Kelantan, Malaysia
Hospital Universiti Sains Malaysia
🇲🇾Kelantan, Malaysia
E-Da Hospital
🇨🇳Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Cheng Ching General Hospital-Chung Kang Branch
🇨🇳Taichung, Taiwan
Hospital Sultana Bahiyah
🇲🇾Alor Setar, Kedah, Malaysia
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Hospital Ampang
🇲🇾Ampang, Selangor, Malaysia
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan County, Taiwan
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
TongJi Hospital of Tongji University
🇨🇳Shanghai, Shanghai, China
2nd Affiliated Hospital, Zhejiang Univ. School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China