Vonoprazan Study of Investigating the Effect on Sleep Disturbance Associated With Reflux Esophagitis- Exploratory Evaluation (VISTAEXE)

• ClinicalTrials.gov Identifier: NCT03116841
• Recruitment Status: Completed
• First Posted: April 17, 2017
• Results First Posted: March 29, 2019
• Last Update Posted: March 29, 2019
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to exploratorily evaluate the effect of vonoprazan 20 mg on sleep disturbance of patients with reflux esophagitis, who have heartburn and/or regurgitation and ≥ 6.0 in the Pittsburgh Sleep Quality Index (PSQI) global score despite the maintenance treatment with PPI other than vonoprazan.

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

Detailed Description:

The purpose of this study is to evaluate the effect of vonoprazan on sleep disturbance in the participants under maintenance treatment for reflux esophagitis with proton pump inhibitor (PPI) other than vonoprazan after initial treatment.

Participants who have been diagnosed as reflux esophagitis based on Los Angeles (LA) Classification Grades A to D, undergoing maintenance treatment with PPI other than vonoprazan after initial treatment, and with Pittsburgh Sleep Quality Index (PSQI) global score >= 6.0 at enrolment (VISIT 1) will be eligible for study entry and will be administered vonoprazan 20 mg once daily for 8 weeks.

Planned number of participants is 25. The study period is 9 weeks. The number of visits is 6visits.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Vonoprazan Study of Investigating the Effect on Sleep Disturbance Associated With Reflux Esophagitis- Exploratory Evaluation (VISTAEXE)
• Actual Study Start Date: August 2, 2017
• Actual Primary Completion Date: December 20, 2017
• Actual Study Completion Date: December 20, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vonoprazan 20 mg; Vonoprazan 20 mg orally administered once daily	Drug: Vonoprazan; Vonoprazan 20 mg

Outcome Measures

Primary Outcome Measures :

1. Changes From Start of Administration (Week 0) in Pittsburgh Sleep Quality Index (PSQI) Global Score at End of Study [ Time Frame: Week 0 to End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participant (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).

Secondary Outcome Measures :

1. Changes From Start of Administration (Week 0) in PSQI Global Score at Week 4 [ Time Frame: From Week 0 to Week 4 ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
2. Percentage of Participants With PSQI Global Score <6.0 at Week 4 and End of Study [ Time Frame: Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality.
3. Changes From Start of Administration (Week 0) in C1: Sleep Quality of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
4. Changes From Start of Administration (Week 0) in C2: Sleep Latency of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
5. Changes From Start of Administration (Week 0) in C3: Sleep Duration of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
6. Changes From Start of Administration (Week 0) in C4: Sleep Efficiency of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
7. Changes From Start of Administration (Week 0) in C5: Sleep Disturbance of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
8. Changes From Start of Administration (Week 0) in C7: Daytime Dysfunction of PSQI Global Score at Week 4 and End of Study [ Time Frame: Week 0, Week 4 and End of study (up to Week 8) ]
   PSQI is a self-rated questionnaire for sleep quality. It includes 18 items across 7 components; C1: Sleep quality, C2: Sleep latency, C3: Sleep duration, C4: Sleep efficiency, C5: Sleep disturbance, C6: Use of sleep medication, C7: Daytime dysfunction. Each component is scored 0-3 (0 = no difficulty, 3=severe difficulty), and total score ranging from 0 to 21. Higher scores are representing worse sleep quality. Reported data were individual scores for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
9. Number of Nocturnal Awakenings Assessed by a Question at Week 4, and End of Study [ Time Frame: Week 4 and End of study (up to Week 8) ]
   Number of nocturnal awakenings was assessed by a question about nocturnal awakenings, "How Many Times Wake Up?" which was asked to each participants by investigator. Reported data were individual times for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
10. Percent Changes From Start of Administration (Week 0) in Actigraph-Measured Sleep Efficiency at Week 4, and End of Study [ Time Frame: Week 4 and End of study (up to Week 8) ]
    Actigraph is a small device usually that records the activity level of the body by sensing physical movement and that is used especially to measure the amount and quality of sleep. Mean value from the past 7 days at each time point was used for calculation. Reported data were individual values for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
11. Changes From Start of Administration (Week 0) in Actigraph-Measured Sleep Latency at Week 4, and End of Study [ Time Frame: Week 4 and End of study (up to Week 8) ]
    Actigraph is a small device usually that records the activity level of the body by sensing physical movement and that is used especially to measure the amount and quality of sleep. Reported data were individual values for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
12. Changes From Start of Administration (Week 0) in Actigraph-Measured Number of Nocturnal Awakenings at Week 4, and End of Study [ Time Frame: Week 4 and End of study (up to Week 8) ]
    Actigraph is a small device usually that records the activity level of the body by sensing physical movement and that is used especially to measure the amount and quality of sleep. Mean value from the past 7 days at each time point was used for calculation. Reported data were individual times for each participants (Participant A to C) since descriptive statistics value was not calculated due to small size population (totally 3 participants).
13. Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to Week 8 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Participants who completed the initial treatment with PPIs (esomeprazole, omeprazole, rabeprazole, or lansoprazole) and have received high dose PPIs (esomeprazole 20 mg, omeprazole 20 mg, rabeprazole 10 mg, or lansoprazole 30 mg) for more than 8 weeks at the time of informed consent as maintenance treatment for LA Classification Grades A to D reflux esophagitis.
2. Participants who have heartburn and/or regurgitation.

3. Participants with reflux esophagitis related sleep disturbance, fulfilling at least one of following in a week before the baseline/start of administration.

   • Difficulty in falling asleep for > = 3 nights
   • Nocturnal awaking or early morning awaking for > = 3 nights
4. Participants whose heartburn and/or regurgitation at the time of informed consent were alleviated from initial treatment.
5. Participants with PSQI global score > = 6.0
6. Participants who, in the opinion of the investigator, are capable of understanding the content of the study and complying with the protocol requirements.
7. Participants who can sign and date an informed consent form and information sheet prior to the initiation of the study procedures.
8. Male or female participants aged 20 years or older at the time of informed consent.
9. Therapeutic category: Ambulatory

Exclusion Criteria:

1. Participants with Zollinger-Ellison syndrome.
2. Participants with diseases that affect sleep (chronic obstructive pulmonary disease, bronchitis asthma, sleep apnea syndrome, mental disorder, etc.)
3. Nightshift workers.
4. Participants who have a plan to travel beyond three time zones during the study.
5. Participants with a history of, concurrent, or suspicious functional dyspepsia or functional heartburn based on Rome IV criteria.
6. Participants with history of surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [except for Schatzki's ring], etc.).
7. 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.
8. Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy.
9. Participants who took antidepressant agents or anti-anxiety agents within 8 weeks before the time of informed consent.
10. Participants who took H2 receptor antagonist within 8 weeks before the time of informed consent.
11. Participants planning to take prohibited concomitant medications during the study period.

12. Participants who have any of the following abnormal clinical laboratory test values at the screening (VISIT 1):

    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN)
    • Bilirubin (Total bilirubin) > ULN
13. Participants with a malignant tumor.
14. Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant.
15. Participants who have serious renal diseases.
16. Participants with the conditions listed under administration contraindication in the vonoprazan package insert.
17. Participants participating in other clinical studies.
18. Participants who have been determined as inappropriate participants by the investigator.

Contacts and Locations

Locations

Japan

Tokatsu Tsujinaka Hospital

Abiko, Chiba, Japan

Amada Clinic

Koriyama, Fukushima, Japan

Aoyama Clinic

Kobe, Hyogo, Japan

Kashiwara Municipal Hospital

Kashiwara, Osaka, Japan

Saino Clinic

Tokorozawa, Saitama, Japan

Masuyama Clinic

Otawara, Tochigi, Japan

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Study Director; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Study Protocol  [PDF] March 28, 2017

Statistical Analysis Plan  [PDF] February 15, 2018

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03116841
• Other Study ID Numbers: Vonoprazan-4006; U1111-1192-9760 ( Registry Identifier: WHO ); JapicCTI-173538 ( Registry Identifier: Japic-CTI )
• First Posted: April 17, 2017
• Results First Posted: March 29, 2019
• Last Update Posted: March 29, 2019
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastroesophageal Reflux; Esophagitis; Esophagitis, Peptic; Dyssomnias; Parasomnias; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases