Efficacy and Safety of Vonoprazan Compared to Lansoprazole in the Maintenance Treatment of Erosive Esophagitis

Erosive Esophagitis Clinical Trial

Official title:

A Randomized, Double-Blind, Double-Dummy, Parallel-group Phase 3 Study to Evaluate the Efficacy and Safety of Oral Once-Daily Administration of TAK-438 10 or 20 mg Compared to Lansoprazole 15 mg in the Maintenance Treatment of Subjects With Endoscopic Healing of Erosive Esophagitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02388737
• Other study ID #: TAK-438_305
• Secondary ID: U1111-1136-5706C
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2015
• Est. completion date: December 31, 2018

Study information

• Verified date: February 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 703
• Est. completion date: December 31, 2018
• Est. primary completion date: December 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 on endoscopy to have had erosive esophagitis [Los Angeles (LA) classification grades A to D] within 84 days of Day 1.

4. 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.

5. 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.

6. 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.

7. 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.

Exclusion Criteria:

1. Has received any investigational compound (other than study TAK-438_303) within 84 days prior to screening phase.

2. Has received TAK-438 in a previous clinical study (other than study TAK-438_303) or as a therapeutic agent.

3. 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.

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 significant central nervous system (CNS), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine or hematological disease.

6. Has a history of hypersensitivity or allergies to TAK-438 or to proton pump inhibitors (PPIs) including any associated excipients.

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 start the screening phase.

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 (other than study TAK-438_303) 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 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.

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 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).

17. 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).

18. Laboratory tests performed on 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).

Related Conditions & MeSH terms

• Erosive Esophagitis
• Esophagitis

Intervention

Drug:
• Vonoprazan
Vonoprazan tablets
• Lansoprazole
Lansoprazole capsules or tablets
• Vonoprazan Placebo
Vonoprazan placebo-matching tablets
• Lansoprazole Placebo
Lansoprazole placebo-matching capsules

Locations

Country	Name	City	State
China	Beijing Chao Yang Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing
China	Beijing Tongren Hospital, Capital Medical Univeristy	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	PLA.The Military General Hospital of Beijing	Beijing
China	The General Hospital of Peoples Armed Police Forces China	Beijing	Beijing
China	No.2 Hospital Affiliated to Jilin University	Changchun	Jilin
China	The 2nd Xiangya Hospital Central South University	Changsha	Hunan
China	The First People's Hospital of Changzhou	Changzhou City	Jiangsu
China	Chenzhou No.1 People's Hospital	Chenzhou	Hunan
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	Fuzhou General Hospital of Nanjing Military Command	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou
China	The Sixth Affiliated Hospital of Sun Yat- Sen University	Guangzhou	Guangdong
China	1st Affiliated Hospital of Zhejiang University	Hangzhou
China	2nd Affiliated Hospital, Zhejiang Univ. School of Medicine	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	China-Japan Union Hospital of Jilin University	Jilin	Jilin
China	Jilin central Hospital	Jilin	Jilin
China	The First Affiated Hospital of Kunming Medical College	Kunming	Yunnan
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Jiangsu Province People's Hospital	Nanjing	Jiangsu
China	The Affiliated DrumTower Hospital of Nanjing University	Nanjing
China	Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.	Shanghai	Shanghai
China	Sixth Peoples Hospital of Shanghai	Shanghai	Shanghai
China	TongJi Hospital of Tongji University	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Jilin Siping Central Hospital	Siping	Jilin
China	The 2nd Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjing	Tianjin
China	Peoples Hospital of Wuhan University	Wuhan	Hubei
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	Xiangtan Central Hospital	Xiangtan	Hunan
China	Yangzhou 1st Hospital	Yangzhou	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Medical Center	Daegu	Gyeongsangbuk-do
Korea, Republic of	Yeungnam University Hospital	Daegu
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	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul
Malaysia	Hospital Sultana Bahiyah	Alor Setar	Kedah
Malaysia	Hospital Ampang	Ampang	Selangor
Malaysia	Hospital Universiti Sains Malaysia	Kelantan
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bahru	Kelantan
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu	Sabah
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Taiwan	E-Da Hospital	Kaohsiung
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan County

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

China,  Korea, Republic of,  Malaysia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Recurrence of Erosive Esophagitis as Confirmed on Endoscopy After the 24-week Maintenance Phase	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	24 weeks
Secondary	Percentage of Participants With Recurrence of Erosive Esophagitis After 12 Weeks of Treatment in the Maintenance Phase	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	12 weeks
Secondary	Number of Participants With Adverse Events (AEs)	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.	From Day 1 to 14 days after the last dose of study medication (up to 26 weeks)
Secondary	Number of Participants With 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.	From Day 1 to 14 days after the last dose of study medication (up to 26 weeks)
Secondary	Number of Participants With 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.	From Day 1 to 14 days after the last dose of study medication (up to 26 weeks)
Secondary	Number of Participants With Abnormal Vital Sign Measurements	The percentage of participants with any markedly abnormal vital sign measurements including (body temperature, blood pressure and pulse), mmHg = millimeters of mercury.	From Day 1 to 14 days after the last dose of study medication (up to 26 weeks)
Secondary	Change From Baseline in Serum Gastrin		Baseline and Weeks 4, 12 and 24
Secondary	Change From Baseline in Serum Pepsinogen I		Baseline and Weeks 4, 12 and 24
Secondary	Change From Baseline in Serum Pepsinogen II		Baseline and Weeks 4, 12 and 24