The Efficacy and Safety Study of Rikkunshito in Patients With Functional Dyspepsia

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of Rikkunshito compared to placebo in Japanese subjects with Functional Dyspepsia (FD).

Official Title
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Double-blind Trial With Rikkunshito Versus Placebo on Efficacy and Safety in Patients With Functional Dyspepsia: Multi-center Study (DREAM Study)

Conditions
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Functional Dyspepsia

Intervention / Treatment
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* Drug: Rikkunshito
* Drug: Rikkunshito placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Patients diagnosed with FD according to the ROME III criteria i) Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to obtaining informed consent ii) Have not received upper endoscopy within the last 6 months prior to enrollment and do not have evidence of structural/organic disease iii) Must have one or more of the following symptoms: Bothersome postprandial fullness Early satiation Epigastric pain Epigastric burning At least one of the FD-related symptoms on the Global Overall Symptom (GOS) scale (bothersome postprandial fullness, early satiation, epigastric pain, epigastric burning) is ≥4, whereas heartburn is ≤3. Total score of depression-related symptoms on Hospital Anxiety and Depression Score (HAD) is ≤10. Type of visit: Outpatient Provides voluntary informed consent after receiving adequate explanation and demonstrates thorough understanding of the nature of the study. Exclusion Criteria: Confirmed ulcer (excluding scars) or malignant tumor in the upper GI Suspected organic lesions in the hepato-biliary-pancreatic regions such as cholelithiasis, hepatitis, pancreatitis History of upper GI resection Serious complications (liver, kidney, heart, or blood disease or metabolic disease) Less than a year since testing positive for H. pylori or have undergone a successful eradication therapy Use of prohibited medications Neuropsychiatric disorders Use of or planned use of any investigational drugs Unable to take drugs orally History of allergic reactions to Kampo medicines Pregnant or lactating women or those who are planning to conceive during the study period Deemed ineligible by principal investigator or sub-investigator

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Rikkunshito Placebo<br> | Drug: Rikkunshito placebo<br>* - Oral administration of rikkunshito placebo (2.5 g t.i.d) before meals for 8 weeks<br>|
| Active Comparator: Rikkunshito<br> | Drug: Rikkunshito<br>* - Oral administration of rikkunshito (2.5 g t.i.d) before meals for 8 weeks<br>* Other names: Tsumura Rikkunshito;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Evaluation of Symptomatic Improvement by Overall Treatment Efficacy (OTE) | Patient's Evaluation of Symptomatic Improvement by OTE is classified into the following 7 categories: Significantly improved Improved Slightly improved No change Slightly worse Worse Much worse The numbers of patients at the final evaluation (i.e, the latest evaluable time point of the all patients including discontinued patients) are shown by category. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (GERD) (Modified FSSG) | The modified FSSG questionnaire is composed of 7 questions regarding GERD symptoms (Questions 1-7, scored from 0 to 4) ranging between 0-28, lower value represents a better outcome, and 7 questions regarding dyspeptic symptoms (Questions 8-14, each question scored from 0 to 4) ranging between 0-28, lower value represents a better outcome, and a total scores, ranging from 0 to 56, lower value represents a better outcome of the all questions (Questions 1-14). Each question was assigned a score based on the frequency of symptoms. The point scores of modified FSSG are calculated from changes from baseline in each score for all symptoms (sum of point scores from Questions 1-14), GERD symptoms, and dyspeptic symptoms at final evaluation. | Baseline and Week 8 | 
| Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) | PAGI-SYM questionnaire is composed of the following 6 categories that consisted of Questions 1 to 20 (each question composed of 6 subscales, i.e., point scores from 0 to 5, lower value represents a better outcome). Subscale scores are calculated by averaging across items in each category. A total score (lower value represents a better outcome, ranging from 0 to 5) is calculated as the mean of the subscale scores. Heartburn/Regurgitation, Nausea/Vomiting, Postprandial Fullness/Early satiety, Bloating, Upper Abdominal Pain, and Lower Abdominal Pain The point scores of PAGI-SYM are calculated from changes from baseline in total score and each category score at final evaluation. | Baseline and Week 8 | 
| Change From Baseline in Global Overall Symptom (GOS) | The GOS scale are calculated by a total score of a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem over 8 questions. The point scores of GOS are calculated from changes from baseline at final evaluation. | Baseline and Week 8 | 
| Change From Baseline in Short-form Health Survey-8 (SF-8) | The SF-8 scores comprised of Physical component summary (PCS) scores (ranging between 5.32-70.69, higher value represents a better outcome) and Mental component summary (MCS) scores (ranging between 10.11-74.51, higher value represents a better outcome), and a total scores of PCS and MCS using a formula specified in SF-8 Scoring Algorithm. The point scores of SF-8 are calculated from changes from baseline in PCS and MCS at final evaluation. | Baseline and week 8 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HAD) | The HAD is a 14-item scale with 2 subscales of depression (Question 1, 3, 5, 7, 9, 11, and 13) and anxiety (Question 2, 4, 6, 8, 10, 12, and 14). Each item on the questionnaire is scored from 0 to 3 (ranging from 0 to 21, lower value represents a better outcome). The point scores of HAD are calculated from changes from baseline in overall (sum of scores for depression and anxiety, i.e., total point score ranging from 0 to 42, lower value represents a better outcome), depression, and anxiety at final evaluation. | Baseline and week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rikkunshito, Double blind, Functional dyspepsia (FD)