Effectiveness and Safety in Administrating CNU® Capsule to Refractory Functional Dyspepsia Patients
Effectiveness and Safety in Administrating CNU® Capsule to Refractory Functional Dyspepsia Patients
Refractory Functional Dyspepsia (FD) means a state that no symptom was improved in spite of
 appropriate treatment for the FD.

 It may be challenging to discriminate the symptoms of FD from the symptoms of bile dyspepsia
 resulting from the biliary system. As the bile dyspepsia may induce epigastralgia as with
 functional dyspepsia and both imaging medical tests and blood tests show normal findings, it
 is difficult to discriminate it from the FD with only these tests.

 Thus this study intends to perform a therapeutic use clinical study for efficacy and safety
 on symptom improvement by administrating CNU capsule to the patients with RFD.
Functional Dyspepsia means a pain or discomfort of epigastrium originated from the stomach or
 duodenum without any causative organic or metabolic disease. For its standard criteria, "Rome
 IV diagnosis criteria" was used, where more than on symptoms including bothersome
 postprandial fullness, early satiation, epigastric pain, and epigastric soreness should have
 been elicited at least 6 months before and continued for at least 3 months in total.

 Refractory Functional Dyspepsia means a state that no symptom was improved in spite of
 appropriate treatment for the functional dyspepsia.

 The pathogenesis of Functional Dyspepsia has not been fully identified yet. Its standard
 therapies include prokinetics, analgesics, H2-receptor antagonists, proton pump inhibitors,
 antacids, serotonin receptor antagonists, proton pump inhibitors, antacids, serotonin
 receptor antagonists, and antidepressants. As these therapies has lower efficacy and drug
 related adverse reactions, the RFD patients who do not respond to medication need another
 therapeutic option.

 It may be challenging to discriminate the symptoms of FD from the symptoms of bile dyspepsia
 resulting from the biliary system. As the bile dyspepsia may induce epigastralgia as with
 functional dyspepsia and both imaging medical tests and blood tests show normal findings, it
 is difficult to discriminate it from the FD with only these tests.

 Therefore even though the epigastralgia or upper abdominal discomfort met the Rome IV
 criteria for the FD, the possibility that it, in part was actually resulted from the bile
 dyspepsia cannot be eliminated.

 The CNU capsule is a choleretic used for bile dyspepsia as a complex agent of trihydrated
 magnesium salt of kenodeoxycholic acid and ursodeoxycholic acid, which are being marketed.

 Thus this study intends to perform a therapeutic use clinical study for efficacy and safety
 on symptom improvement by administrating CNU capsule to the patients with RFD.
Inclusion Criteria:

 1. Person over 19 years old as of the date of submission

 2. Among patients with FD diagnosed by the Rome IV criteria, patients with RFD

 -  Person who have had early satiation and bothersome postprandial fullness for
 minimum 3 days a week and epigastric pain and epigastric soreness for minimum 1
 day a week

 -  Person with above symptoms that started at least 6 months before and continused
 for minimum 3 months

 -  Person having no possible causes of above symptoms including organic disease,
 structural modification, systemic disease, and endocrinology-metabolic disease

 -  Person who do not respond to at least 2 general treatments for FD

 -  Dyspepsia symptoms that can disrupt daily life (global overall symptom scale
 score =>5)

 3. Persons who submitted written consent to participate in this study

 Exclusion Criteria:

 1. Patient with biliary disease other than bile stone, scraps in the gall and bile tract,
 and polyps of gallbladder

 2. Patient with structurally abnormal biliary system from congenital malformation or
 other reasons

 3. Patients with endocrinology-metabolic disease that can affect mobility of
 gastrointestinal tract and biliary system such as diabetes and abnormal thyroid
 function

 4. Patient who cannot discontinue any drug that can provoke abdominal symptoms

 5. Patient with disease or damage in central nervous system (cerebral hemorrhage and
 cerebral infarction with residual disorder) and autonomic nervous system (vertebrate)

 6. Patient with renal disorder and electrolyte imbalance

 7. Patient who received gastrointestinal surgery (excluding appendectomy and
 hemorrhoidectomy)

 8. Patient with frequent biliary colic or infection of biliary infection

 9. Obstructive jaundice patient

 10. Severe renal disease patient

 11. Patient with variceal bleeding, hepatic coma, ascites, and needs for acute liver
 transplantation

 12. Patient with severe pancreatic disease

 13. Person scheduled to receive combined administration of below drugs:

 -  Drug with considerable hepatic toxicity Antacid agent containing cholestyramine,
 medical charcoal, magnesium and aluminum hydroxide

 -  alpha-methydopa

 -  Drug to increase bile secretion of cholesterol ( estrogen, hormonal contraception
 agent, partial lipid lowering agent), drug to reduce blood cholesterol

 14. Patient with hypersensitivity to this drug or any component of this drug

 15. Patient with severe biliary obstruction

 16. Patient with radiopaque, calcificated bile stone

 17. Patient with acute cholecystitis

 18. Patient with peptic ulcer

 19. Patient with coloenteritis like Crohn disease

 20. Cholestasis patient

 21. Patient with abnormality in gallbladder contraction (below 40% of GB ejection
 fraction)

 22. Person relevant to below criteria, as results of tests conducted in screening

 -  Person with BUN exceeding 3 times of normal upper limit

 -  Person with blood creatinine exceeding 3 times of normal upper limit

 -  Person with total bilirubin exceeding 3 times of normal upper limit

 -  Person with direct bilirubin exceeding 3 times of normal upper limit

 -  Person with AST(sGOT) and ALT(sGPT) exceeding 3 times of normal upper limit

 -  Person with ALP(alkaline phosphatase) exceeding 3 times of normal upper limit

 -  Person with GGT(gamma-glutamyl transferase) exceeding 3 times of normal upper
 limit

 23. Woman who is pregnant or lactating and women in childbearing age who uses no reliable
 contraceptive measure or doesn't agree to keep contraception during pregnancy period

 24. Person who cannot understand purpose and methods of this study such as mental patients
 or patients with drug and alcohol abuse

 25. Other persons considered by any investigator to have some difficulties in performing
 this study