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

Phase 4

Completed

• Conditions: Reflux Esophagitis
• Interventions: Drug: Vonoprazan

• Registration Number: NCT03116841
• Lead Sponsor: Takeda

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.

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 Timeline

• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-12
• Study First Posted: 2017-04-17
• Study Start: 2017-08-02
• Primary Completion: 2017-12-20
• Study Completion: 2017-12-20
• Status Verified: 2018-12
• Results First Submitted: 2018-12-20
• Results First Submitted QC: 2018-12-20
• Last Update Submitted: 2018-12-20
• Results First Posted: 2019-03-29
• Last Update Posted: 2019-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vonoprazan 20 mg	Vonoprazan	Vonoprazan 20 mg orally administered once daily

Primary Outcome Measures

Name	Time	Method
Changes From Start of Administration (Week 0) in Pittsburgh Sleep Quality Index (PSQI) Global Score at End of Study	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

Name	Time	Method
Changes From Start of Administration (Week 0) in C2: Sleep Latency of PSQI Global Score at Week 4 and End of Study	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).
Changes From Start of Administration (Week 0) in C3: Sleep Duration of PSQI Global Score at Week 4 and End of Study	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).
Changes From Start of Administration (Week 0) in C7: Daytime Dysfunction of PSQI Global Score at Week 4 and End of Study	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).
Number of Nocturnal Awakenings Assessed by a Question at Week 4, and End of Study	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).
Percent Changes From Start of Administration (Week 0) in Actigraph-Measured Sleep Efficiency at Week 4, and End of Study	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).
Changes From Start of Administration (Week 0) in Actigraph-Measured Number of Nocturnal Awakenings at Week 4, and End of Study	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).
Changes From Start of Administration (Week 0) in PSQI Global Score at Week 4	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).
Percentage of Participants With PSQI Global Score <6.0 at Week 4 and End of Study	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.
Changes From Start of Administration (Week 0) in C1: Sleep Quality of PSQI Global Score at Week 4 and End of Study	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).
Changes From Start of Administration (Week 0) in C4: Sleep Efficiency of PSQI Global Score at Week 4 and End of Study	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).
Changes From Start of Administration (Week 0) in C5: Sleep Disturbance of PSQI Global Score at Week 4 and End of Study	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).
Changes From Start of Administration (Week 0) in Actigraph-Measured Sleep Latency at Week 4, and End of Study	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).
Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)	Up to Week 8

Trial Locations

Locations (6)

Tokatsu Tsujinaka Hospital; 🇯🇵 Abiko, Chiba, Japan

Aoyama Clinic; 🇯🇵 Kobe, Hyogo, Japan

Saino Clinic; 🇯🇵 Tokorozawa, Saitama, Japan

Kashiwara Municipal Hospital; 🇯🇵 Kashiwara, Osaka, Japan

Amada Clinic; 🇯🇵 Koriyama, Fukushima, Japan

Masuyama Clinic; 🇯🇵 Otawara, Tochigi, Japan