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

Erosive Esophagitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02388724
• Other study ID #: TAK-438_303
• Secondary ID: U1111-1138-4788C
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2015
• Est. completion date: July 27, 2017

Study information

• Verified date: February 2019
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 481
• Est. completion date: July 27, 2017
• Est. primary completion date: July 27, 2017
• 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 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.

Related Conditions & MeSH terms

• Erosive Esophagitis
• Esophagitis

Intervention

Drug:
• Vonoprazan
Vonoprazan tablets
• Lansoprazole
Lansoprazole capsules
• 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	China-Japan Friendship hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	PLA.The Military General Hospital of Beijing	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	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	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	TongJi Hospital of Tongji University	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	The 2nd Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
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	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	Cheng Ching General Hospital-Chung Kang Branch	Taichung
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 Endoscopic Healing of Erosive Esophagitis During the 8-Week Treatment Phase	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.	8 weeks
Secondary	Percentage of Participants With Endoscopic Healing of Erosive Esophagitis After 2 Weeks and 4 Weeks of Treatment	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.	Week 2 and Week 4
Secondary	Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)	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.	On or after the start of study drug (Day 1) to 14 days after the last dose of study medication (up to 10 weeks)
Secondary	Number of Participants With Markedly 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 10 weeks)
Secondary	Number of Participants With Markedly 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 10 weeks)
Secondary	Number of Participants With Markedly Abnormal Vital Sign Measurements	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.	From Day 1 to 14 days after the last dose of study medication (up to 10 weeks)
Secondary	Change From Baseline in Serum Gastrin	The change between the serum gastrin values collected at Weeks 2, 4, and 8 relative to baseline.	Baseline and Weeks 2, 4, and 8
Secondary	Change From Baseline in Serum Pepsinogen I	The change between the serum pepsinogen I values collected at Weeks 2, 4, and 8 relative to baseline.	Baseline and Weeks 2, 4, and 8
Secondary	Change From Baseline in Serum Pepsinogen II	The change between the serum pepsinogen II values collected at Weeks 2, 4, and 8 relative to baseline.	Baseline and Weeks 2, 4, and 8