Effectiveness and Safety in Administrating CNU® Capsule to Refractory Functional Dyspepsia Patients

Multi-center Single Sided Preliminary Study to Evaluate 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.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Biliary Dysplasia
• Intervention / Treatment: Drug: efficacy and safety of CNU® Capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bundang-gu
    • Seongnam, Bundang-gu, Korea, Republic of, 13496
      • CHA Bundang Medical Center
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06229
      • Gangnam Severance Hospital
  • Gyeonggi-do
    • Hwaseong-si, Gyeonggi-do, Korea, Republic of, 18450
      • Dongtan Sacred Heart Hospital
  • Jung-gu
    • Incheon, Jung-gu, Korea, Republic of, 22332
      • In Ha University Hospital
  • Namdong-gu
    • Cheonan, Namdong-gu, Korea, Republic of, 31151
      • Soon Chun Hyang University Hospital, Cheonan
    • Incheon, Namdong-gu, Korea, Republic of, 21565
      • Gachon University Gil Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with Refractory Functional Dyspepsia; Patients with FD diagnosed by the Rome IV criteria, patients with Refractory Functional Dyspepsia; 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)

Drug: efficacy and safety of CNU® Capsule; All subjects take 250mg CNU capsule orally 1 capsule per time, 2 times a day (morning, evening / at meal or after meal) for 12 weeks.; Other Names: CNU® Capsule (Trihydrated magnesium salt of kenodeoxycholic acid and ursodeoxycholic acid, 250 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of symptoms	The primary outcome variable will be the percentage of subjects to report that they are improved or unchanged or deteriorated or No assessable in overall symptoms compared to baseline on a 7-point Global Overall Symptom Scale (GOS). The GOS is assessed on a 7-point scale, with the severity scale from 1 (Normal, not at all ill) through to 7 (Among the most severely ill patients).	12weeks after CNU capsules

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Total Number of subjects Experiencing at Least one Adverse Event During the study	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	for 12 weeks

Collaborators and Investigators

• Sponsor: Gangnam Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): August 4, 2021
• Study Completion (Actual): August 4, 2021

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Refractory Functional Dyspepsia
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: 3-2018-0300

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: The data will become available untill all patients are enrolled and be open to all researchers for 1 year
• IPD Sharing Access Criteria: Only researchers.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No