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Vonoprazan Study in Patients With Erosive Esophagitis to Evaluate Long-term Safety

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ClinicalTrials.gov Identifier: NCT02679508
Recruitment Status : Active, not recruiting
First Posted : February 10, 2016
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration (260 weeks: 5 years) of vonoprazan 10 mg or 20 mg in patients receiving maintenance treatment after healed erosive esophagitis (EE), and the curative effect of vonoprazan 20 mg versus lansoprazole in patients with EE.

Condition or disease Intervention/treatment Phase
Erosive Esophagitis Drug: Vonoprazan Drug: Lansoprazole Phase 4

Detailed Description:

This is a multicenter, open-label, randomized, parallel-group study to exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration of vonoprazan in maintenance treatment after healed EE, and the curative effect of vonoprazan versus lansoprazole in participants with EE.

Participants endoscopically diagnosed with EE of Los Angeles (LA) Classification Grades A to D at the start of treatment (Week 0 of the healing phase) will be randomly assigned to receive either vonoprazan 20 mg or lansoprazole 30 mg to be taken once daily for up to 8 weeks. Subjects with healed EE as confirmed endoscopically at Week 4 or 8 in the healing phase will enter the maintenance phase.

In the maintenance phase, the vonoprazan group and the lansoprazole group will be administered a starting dose of 10 mg and 15 mg, respectively, once daily up to 260 weeks.

If the principal investigator or investigator judged the effect of vonoprazan 10 mg or lansoprazole 15 mg to be insufficient as the maintenance treatment of EE, vonoprazan and lansoprazole may be increased to 20 mg and 30 mg, respectively.

The research period will consist of two subperiods: healing phase in which participants with EE will receive treatment (for 4 or 8 weeks) and maintenance phase in which participants will receive maintenance treatment (for 260 weeks), and thus, a total of up to 268 weeks. The number of visits will be a maximum of 18 visits. Planned number of research subjects, as the number of research subjects for entry to the maintenance phase, will be 130 participants in the vonoprazan group and 65 participants in the lansoprazole group.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Vonoprazan Study In Patients With Erosive Esophagitis to Evaluate Long-term Safety: A Study to Evaluate the Safety of Long-term Administration of Vonoprazan in Maintenance Treatment in Patients With Erosive Esophagitis (EE)
Actual Study Start Date : March 29, 2016
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vonoprazan group
Vonoprazan 20 mg administered orally once daily in the healing phase + vonoprazan 10 mg (as the initial dose and adjusted to vonoprazan 10 mg or 20 mg) administered orally once daily in the maintenance phase
Drug: Vonoprazan
Vonoprazan fumarate 10 mg or 20 mg capsules

Active Comparator: Lansoprazole group
Lansoprazole 30 mg administered orally once daily in the healing phase + lansoprazole 15 mg (as the initial dose and adjusted to lansoprazole 15 mg or 30 mg) administered orally once daily in the maintenance phase
Drug: Lansoprazole
Lansoprazole 15 mg or 30 mg capsules




Primary Outcome Measures :
  1. Percentage of participants with clinically significant Gastric mucosa histopathology findings [ Time Frame: Up to Week 268 ]
    For each gastric mucosa histopathological endpoint (presence or absence of malignant alteration of epithelial cells, presence or absence of prominence/hyperplasia of wall cells, presence or absence of hyperplasia of crypt epithelial cells, presence or absence of proliferation of endocrine cells, and presence or absence of hyperplasia of G cells), the proportion of research participants who have the events for assessment in maintenance phase shall be calculated for each treatment group.


Secondary Outcome Measures :
  1. Endoscopic erosive esophagitis (EE) recurrence rate [ Time Frame: Up to Week 268 ]
  2. EE healing rate at the end of the healing phase [ Time Frame: Up to Week 8 ]
  3. Number of Participants Reporting One or More Treatment-emergent Adverse Events [ Time Frame: Up to Week 268 ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; 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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  4. Percentage of participants with clinically significant endoscopic findings [ Time Frame: Up to Week 268 ]
    For each endoscopic endpoint (presence or absence of fundic gland polyp, presence or absence of hyperplastic polyp, presence or absence of cobblestone mucosa, presence or absence of multiple white flat elevation, and presence or absence of black spots), the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.

  5. Percentage of participants with clinically significant histological evaluation of gastritis according to the Sydney classification [ Time Frame: Up to Week 268 ]
    For each histological endpoint of gastritis according to the Sydney classification [inflammation (mononuclear infiltration), activity (neutrophilic infiltration), atrophy, intestinal metaplasia, and H. pylori], the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.

  6. Percentage of participants who have gastric polyp in maintenance phase [ Time Frame: Up to Week 268 ]
    For gastric polyp, the proportion of research participants who have gastric polyp in maintenance phase of this study shall be calculated for each treatment group.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Healing Phase:

  1. Participants endoscopically diagnosed with EE of grades A to D by the LA Classification Grading System at the start of treatment (Week 0 of the healing phase)
  2. Participants with H. pylori negative
  3. Participants who, in the opinion of the principal investigator or investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements.
  4. Participants who can sign and date an informed consent form and information sheet prior to the conduction of the clinical research procedures.
  5. Male or female participants aged 20 years or older at the time of informed consent
  6. Therapeutic category: Ambulatory

    Maintenance Phase:

  7. Participants who have endoscopically confirmed EE healing* (mucous membrane disorder is not observed) at completion of the healing phase (Week 4 or 8 of the healing phase)

    * Participants who are classified as grade 0 according to severity classification of EE (See Table 9.b)

  8. Participants who have been determined to be appropriate as subjects for maintenance treatment of EE by the principal investigator or investigator

Exclusion Criteria:

Healing Phase:

  1. Participants with concurrent peptic ulcer (except scarred stage) or Zollinger-Ellison syndrome
  2. Participants who received treatment with PPIs (including vonoprazan) within 4 weeks (Week -4 to Week 0) prior to the start of healing phase (Week 0 of the healing phase)
  3. Participants with a history of H. pylori eradication.
  4. Participants who have received surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [excluding Schatzki's ring], etc.)
  5. Participants with an esophagus-related complication (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis, etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or Barrett's esophagus are allowed to be included.
  6. Participants with clinically apparent hepatic impairment (e.g., AST or ALT levels at the time of informed consent: >1.5 times the upper limit of normal (ULN).
  7. Participants with renal impairment or renal failure [creatinine clearance (CCr) ˂30 mL/min, etc.]
  8. Participants with a history of hypersensitivity or allergy for PPIs.
  9. Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy
  10. Participants with a malignant tumor
  11. Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant
  12. Participants with one of the diseases listed under administration contraindication in the vonoprazan or lansoprazole package insert
  13. Participants planning to take prohibited concomitant medications during the research period
  14. Participants participating in other clinical studies
  15. Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

    Maintenance Phase:

  16. Participants who have taken PPIs other than the study drug or the control drug during the healing phase
  17. Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02679508


Locations
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Japan
Tokatsu Tsujinaka Hospital
Abiko, Chiba, Japan
Hohnodai Hospital National Center For Global Health and Medicine
Ichikawa, Chiba, Japan
Red Cross Matsuyama Hospital
Matsuyama, Ehime, Japan
Kawakubo Clinic
Kama, Fukuoka, Japan
Hakodate Hospital
Hakodate, Hokkaido, Japan
Aoyama Medical Clinic
Kobe, Hyogo, Japan
Hyogo College Of Medicine
Nishinomiya, Hyogo, Japan
KKR Takamatsu Hospital
Takamatsu, Kagawa, Japan
Shirane Clinic
Sendai, Miyagi, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
Shin-Beppu Hospital
Beppu, Oita, Japan
Kawasaki Medical University
Kurashiki, Okayama, Japan
Shiga Hospital
Otsu, Shiga, Japan
Shiga University Of Medical Science Hospital
Otsu, Shiga, Japan
Shimane University Hospital
Izumo, Shimane, Japan
Juntendo University Shizuoka Hospital
Izunokuni, Shizuoka, Japan
Kohga Hospital
Yaizu, Shizuoka, Japan
Masuyama Clinic
Otawara, Tochigi, Japan
Juntendo University Hospital
Bunkyo-ku, Tokyo, Japan
Banno Clinic
Ota-ku, Tokyo, Japan
Shimokitazawa Tomo Clinic
Setagaya-ku, Tokyo, Japan
National Center For Global Health and Medicine
Shinjyuku-ku, Tokyo, Japan
Nippon Medical School Hospital
Shinjyuku-ku, Tokyo, Japan
Chihaya Hospital
Fukuoka, Japan
Harada Hospital
Fukuoka, Japan
Kimura Shiro Clinic
Fukuoka, Japan
Kyushu University Hospital
Fukuoka, Japan
Mori Clinic
Fukuoka, Japan
Hanabata Clinic
Kumamoto, Japan
Morinaga Ueno Clinic
Kumamoto, Japan
Oki Hospital
Kyoto, Japan
Arita Hospital
Oita, Japan
Asahigaoka Hospital
Okayama, Japan
Kawasaki Hospital
Okayama, Japan
Matsuki Clinic
Shizuoka, Japan
Oizumi Medical Clinic
Yamagata, Japan
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Takeda Pharmaceuticals Limited

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02679508     History of Changes
Other Study ID Numbers: Vonoprazan-4003
U1111-1178-8948 ( Registry Identifier: WHO )
JapicCTI-163153 ( Registry Identifier: JapicCTI )
First Posted: February 10, 2016    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Keywords provided by Takeda:
Esophagitis
Additional relevant MeSH terms:
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Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Lansoprazole
Dexlansoprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action