Efficacy and Safety of Vonoprazan Compared to Lansoprazole in the Maintenance Treatment of Erosive Esophagitis
- Conditions
- Erosive Esophagitis
- Interventions
- Registration Number
- NCT02388737
- Lead Sponsor
- Takeda
- Brief Summary
This is a comparative study of vonoprazan (TAK-438) (10 mg or 20 mg) in participants in whom endoscopic healing of erosive esophagitis has been confirmed with vonoprazan or adequate treatment with a proton pump inhibitor (PPI), to demonstrate the non-inferiority of vonoprazan to lansoprazole in their maintenance treatment (6 months or 24 weeks) as well as to determine the clinically recommended dose for vonoprazan for maintenance therapy in erosive esophagitis.
- Detailed Description
The drug being tested in this study is called vonoprazan. Vonoprazan is being tested as a maintenance treatment for people with healed erosive esophagitis (EE). This study will look at participants in whom endoscopic healing of erosive esophagitis has been confirmed with vonoprazan or adequate treatment with a proton pump inhibitor (PPI), to demonstrate the non-inferiority of vonoprazan to Lansoprazole in their maintenance treatment (6 months or 24 weeks) as well as to determine the clinically recommended dose for vonoprazan for maintenance therapy in erosive esophagitis.
The study will enroll approximately 693 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
* TAK-438 10 mg
* TAK-438 20 mg
* Lansoprazole 15 mg
Participants with ongoing erosive esophagitis (EE) will receive lansoprazole 30 mg once daily for 4 or 8 weeks (the Healing phase) until healing of EE is confirmed by endoscopy performed at either Week -4 and/or Day 1 before eligible for randomization to maintenance phase. In Maintenance phase, participants with confirming EE healing will be asked to take 2 tablets and a capsule at the same time each morning after breakfast 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-centre trial will be conducted worldwide. The overall time to participate in this study is 8 months. 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
- 703
- In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- 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.
- Has been confirmed on endoscopy to have had erosive esophagitis [Los Angeles (LA) classification grades A to D] within 84 days of Day 1.
- If the participant is not rolled over from TAK-438_303 study, he/she has undergone an open-label Proton pump inhibitor (PPI) treatment (Lansoprazole 30 mg, once daily) of 4 or 8 weeks within the TAK-438_305 protocol.
- Has been confirmed on endoscopy to have healing of erosive esophagitis. This endoscopy, if not part of the TAK-438_303 study, must have been within the last 14 days prior to randomization, otherwise the endoscopy must be repeated to confirm healing before randomization in the TAK-438_305 study.
- 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 temporarily admitted for examination.
- 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 and for 4 weeks after last dose of study medication.
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Has received any investigational compound (other than study TAK-438_303) within 84 days prior to screening phase.
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Has received TAK-438 in a previous clinical study (other than study TAK-438_303) or as a therapeutic agent.
-
Is an immediate family member, study site employee, or is in a dependent 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 significant central nervous 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 or to proton pump inhibitors (PPIs) including any associated excipients.
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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 start the screening phase.
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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 (other than study TAK-438_303) 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 Screening Phase (Visit 1) (with the possible inclusion of those with gastric or duodenal erosion). Participants requiring non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin treatment along with the concomitant PPI therapy to prevent gastrointestinal (GI) bleeding should not be enrolled.
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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 Screening 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] 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 on 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vonoprazan 10 mg Lansoprazole Placebo Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 10 mg, tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg placebo-matching, capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Vonoprazan 20 mg Vonoprazan Placebo Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 20 mg, tablets, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg, placebo-matching capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing Vonoprazan 20 mg Lansoprazole Placebo Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 20 mg, tablets, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg, placebo-matching capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing Vonoprazan 10 mg Vonoprazan Placebo Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 10 mg, tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg placebo-matching, capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Lansoprazole 15 mg Vonoprazan Placebo Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Lansoprazole 15 mg, capsules, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Vonoprazan 10 mg Lansoprazole Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 10 mg, tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg placebo-matching, capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Vonoprazan 10 mg Vonoprazan Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 10 mg, tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg placebo-matching, capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Vonoprazan 20 mg Vonoprazan Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 20 mg, tablets, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg, placebo-matching capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing Lansoprazole 15 mg Lansoprazole Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Lansoprazole 15 mg, capsules, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Vonoprazan 20 mg, placebo-matching tablets, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing. Vonoprazan 20 mg Lansoprazole Lansoprazole 30 mg, capsules or tablets, orally, once, daily, for up to 4 or 8 weeks or until confirmed healing of erosive esophagitis (EE) in healing phase for participants with ongoing EE. Vonoprazan 20 mg, tablets, orally, once, daily, and Vonoprazan 10 mg, placebo-matching tablets, orally, once, daily, and Lansoprazole 15 mg, placebo-matching capsules, orally, once, daily, for up to 24 weeks in maintenance phase for participants with confirmed EE healing
- Primary Outcome Measures
Name Time Method Percentage of Participants With Recurrence of Erosive Esophagitis as Confirmed on Endoscopy After the 24-week Maintenance Phase 24 weeks Erosive esophagitis recurrence is defined as participants endoscopically confirmed to have erosive esophagitis (Los Angeles \[LA\] classification grades A to D) during the Maintenance Phase (24 weeks). Grade A: \>/=1 mucosal breaks \</=5 mm, none of which extends between the tops of the mucosal folds; Grade B: \>/=1 mucosal breaks \>5 mm, none of which extends between the tops of two mucosal folds; Grade C: mucosal breaks that extend between the tops of two or more mucosal folds, but which involve \<75% of esophageal circumference; Grade D: mucosal breaks which involve \>/=75% of esophageal circumference.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) From Day 1 to 14 days after the last dose of study medication (up to 26 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 Abnormal Electrocardiogram (ECG) Findings From Day 1 to 14 days after the last dose of study medication (up to 26 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 With Abnormal Vital Sign Measurements From Day 1 to 14 days after the last dose of study medication (up to 26 weeks) The percentage of participants with any markedly abnormal vital sign measurements including (body temperature, blood pressure and pulse), mmHg = millimeters of mercury.
Change From Baseline in Serum Pepsinogen II Baseline and Weeks 4, 12 and 24 Percentage of Participants With Recurrence of Erosive Esophagitis After 12 Weeks of Treatment in the Maintenance Phase 12 weeks Erosive esophagitis recurrence is defined as endoscopically confirmed to have erosive esophagitis (LA classification grades A to D) during the Maintenance Phase (12 weeks). Grade A: \>/=1 mucosal breaks \</=5 mm, none of which extends between the tops of the mucosal folds; Grade B: \>/=1 mucosal breaks \>5 mm, none of which extends between the tops of two mucosal folds; Grade C: mucosal breaks that extend between the tops of two or more mucosal folds, but which involve \<75% of esophageal circumference; Grade D: mucosal breaks which involve \>/=75% of esophageal circumference.
Change From Baseline in Serum Pepsinogen I Baseline and Weeks 4, 12 and 24 Number of Participants With Abnormal Clinical Laboratory Findings From Day 1 to 14 days after the last dose of study medication (up to 26 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.
Change From Baseline in Serum Gastrin Baseline and Weeks 4, 12 and 24
Trial Locations
- Locations (70)
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Hospital Ampang
🇲🇾Ampang, Selangor, Malaysia
Beijing Chao Yang Hospital
🇨🇳Beijing, Beijing, China
Hospital Universiti Sains Malaysia
🇲🇾Kelantan, Malaysia
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan County, Taiwan
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
E-Da Hospital
🇨🇳Kaohsiung, Taiwan
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Fuzhou General Hospital of Nanjing Military Command
🇨🇳Fuzhou, Fujian, China
The Sixth Affiliated Hospital of Sun Yat- Sen University
🇨🇳Guangzhou, Guangdong, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
The General Hospital of Peoples Armed Police Forces China
🇨🇳Beijing, Beijing, China
Beijing Tongren Hospital, Capital Medical Univeristy
🇨🇳Beijing, Beijing, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Techology
🇨🇳Wuhan, Hubei, China
Union Hospital of Tongji Medical College of Huazhong Science and Techology University
🇨🇳Wuhan, Hubei, China
Peoples Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
The 2nd Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Chenzhou No.1 People's Hospital
🇨🇳Chenzhou, Hunan, China
Xiangtan Central Hospital
🇨🇳Xiangtan, Hunan, China
The First People's Hospital of Changzhou
🇨🇳Changzhou City, Jiangsu, China
Jiangsu Province People's Hospital
🇨🇳Nanjing, Jiangsu, China
No.2 Hospital Affiliated to Jilin University
🇨🇳Changchun, Jilin, China
Yangzhou 1st Hospital
🇨🇳Yangzhou, Jiangsu, China
China-Japan Union Hospital of Jilin University
🇨🇳Jilin, Jilin, China
Jilin central Hospital
🇨🇳Jilin, Jilin, China
Jilin Siping Central Hospital
🇨🇳Siping, Jilin, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
TongJi Hospital of Tongji University
🇨🇳Shanghai, Shanghai, China
Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University General Hospital
🇨🇳Tianjing, Tianjin, China
Sixth Peoples Hospital of Shanghai
🇨🇳Shanghai, Shanghai, China
The 2nd Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
The First Affiated Hospital of Kunming Medical College
🇨🇳Kunming, Yunnan, China
2nd Affiliated Hospital, Zhejiang Univ. School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
🇨🇳Hangzhou, Zhejiang, China
PLA.The Military General Hospital of Beijing
🇨🇳Beijing, China
The Second Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, China
1st Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China
The First Affiliated Hospital of NanChang University
🇨🇳Nanchang, China
Seoul National University Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
The Affiliated DrumTower Hospital of Nanjing University
🇨🇳Nanjing, 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
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Sultana Bahiyah
🇲🇾Alor Setar, Kedah, Malaysia
Hospital Raja Perempuan Zainab II
🇲🇾Kota Bahru, Kelantan, Malaysia
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Sabah, Malaysia
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of