Clinical Trial of Efficacy and Safety of Kolofort in Functional Dyspepsia Patients

Study Overview
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Brief Summary
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Purpose of the study: To obtain additional data on efficacy and safety of Kolofort in the treatment of patients with functional dyspepsia.

Detailed Description
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Design: a multicenter double-blind placebo-controlled randomized clinical trial to evaluate the efficacy and safety of the study treatment. The study will enroll the patients of both genders aged 18-45 years old with verified diagnosis of functional dyspepsia according to Rome-IV criteria and intensity of dyspeptic symptoms ≥ 6 according to GIS (Gastrointestinal symptom score). At the screening visit 1 (Visit 1, from -14 to -1 days), after signing patient information sheet (informed consent form) to participate in the clinical trial, complaints and medical history are collected, an objective examination is performed. The investigator evaluates intensity of dyspeptic symptoms according to GIS. The patient undergoes an abdomen ultrasound examination, esophagogastroduodenoscopy (EGDS) , and diagnostic tests for Helicobacter pylori (H. pylori) infection. In case of the previous use of proton pump inhibitors, prokinetics, antispasmodics, antacids, bismuth drugs the investigator evaluates the possibility of canceling these drugs at least 7 days before the patient is randomized. For women of reproductive age, a pregnancy test is performed. On the day of randomization (Visit 2, Day 0) collection of complaints and objective examination are carried out. The investigator evaluates the results of laboratory and instrumental research methods, the severity of dyspepsia symptoms on the GIS scale, registers changes in concomitant therapy. If a patient meets all inclusion criteria and does not have any exclusion criteria, he/she is randomized into one of two groups: patients in Group 1 receive Kolofort for 8 weeks; patients in Group 2 - Placebo on the study drug regimen. The patient completes the Nepean Dyspepsia Index (NDI) and Quality of Life (SF-36) questionnaires. The patient's treatment lasts for 8 weeks, during which 3 visits to the research center are carried out. At Visit 3 (Week 2 ± 3 days), complaints are collected, an objective examination of the patient is performed. The investigator monitors the prescribed and concomitant therapy, evaluates the safety of therapy and the degree of adherence to treatment (compliance). At visit 4 (week 4±3 days) and 5 (week 8±3 days) the investigator collects complaints, registers the physical examination data, monitors the prescribed and concomitant therapy, assesses the safety of the treatment and compliance. Questionnaires GIS, NDI are filled in. Additionally, at Visit 5 the patient fills out the SF-36 scale, the investigator fills out the Clinical Global Impression-Efficacy Index (CGI-EI). The patients will be allowed to take symptomatic therapy and medications for their co-morbidities during the study, except for the medicines listed in Prohibited Concomitant Treatment.

Official Title
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Multicenter Double-blind Placebo-controlled Randomized Clinical Trial of Efficacy and Safety of Kolofort in the Treatment of Patients With Functional Dyspepsia

Conditions
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Dyspepsia

Intervention / Treatment
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* Drug: Kolofort
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both genders aged 18-45 years old. Diagnosis of functional dyspepsia established according to Rome-IV criteria (2016). Severity of symptoms of dyspepsia ≥ 6 on the GIS scale. Negative test result for H. pylori infection . Availability of signed patient information sheet and informed consent form for participation in the clinical trial. Patients who gave their consent to use reliable contraception during the study Exclusion Criteria: Organic diseases of the gastrointestinal tract (gastroesophageal reflux disease (GERD), peptic ulcer, chronic pancreatitis, cholelithiasis, hepatosis, hepatitis, hepatic cirrhosis, etc.) Verified diagnosis of other functional GI diseases, i.e. biliary dyskinesia, irritable bowel syndrome, etc. Discontinuation of proton pump inhibitors, prokinetics, antispasmodics, antacids, bismuth preparations less than 7 days before randomization. H. pylori eradication within 2 months prior to enrollment. Intestinal infection within 2 months prior to enrollment. History/suspicion of oncology of any location. Previously diagnosed cardiovascular diseases with functional class IV (according to the classification of the New-York Heart Association, 1964), hypothyroidism, diabetes mellitus, chronic renal disease С3-5, hepatic diseases with portal hypertension and/or signs of severe decompensation of function (> 6 points according to the Child-Pugh classification). Any other severe comorbidity that, in the opinion of the investigator, may affect patient participation in the clinical trial. Allergy/intolerance intolerances to any of the components of the study drugs. Pregnancy, breast-feeding. Patients who, from the investigator's point of view, will not comply with the observation requirements of the study or adhere to study drug dosing regimens. Scheduled hospitalization during the study for any diagnostic or therapeutic procedures. Use of drugs or alcohol (more than 2 alcohol units daily), presence of mental diseases. Use of any medications specified in the Prohibited Concomitant Treatment within 1 month prior to inclusion in the study. Participation in other clinical trials in the previous 3 months. Patients who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted). Patients who work for MATERIA MEDICA HOLDING (i.e. the company's employees, temporary contract workers, appointed officials responsible for carrying out the research or immediate relatives of the aforementioned).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Experimental: Kolofort<br>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets per day). The tablets should be held in the mouth until complete dissolution, without meal. | Drug: Kolofort<br>* Oral administration<br>|
| Placebo Comparator: Placebo<br>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets per day). The tablets should be held in the mouth until complete dissolution, without meal. | Drug: Placebo<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Severity of Functional Dyspepsia Symptoms | Changes in severity of functional dyspepsia symptoms due to GIS score (Gastrointestinal symptom score) at week 8 from the start of study therapy. The GIS scale includes 10 subscales (symptoms), the severity of each one was evaluated from 0 to 4 points (by Lickert scale).For example, the absence of the mentioned symptom is classified as 0. The most severe is classified as 4. The all 10 subscales were combined to compute a total score. So the total range is a sum of all subscales.The total score is in range from 0 till 40. So the minimum value is 0, the maximum is 40. | On baseline, after 4 and 8 weeks of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a Decrease in the Severity of FD Symptoms | Percentage of patients with a decrease in the severity of FD symptoms on the GIS scale after 8 weeks from the start of study therapy. The GIS scale is composed of 10 points evaluating the extent of manifestation of a wide range of gastroenterological symptoms. The intensity of clinical symptoms will be evaluated based on a 5-point Likert scale from 0 to 4 where 0 = no, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe). | After 8 weeks of the treatment | 
| Change in the Severity of the Functional Dyspepsia Index NDI (Nepean Dyspepsia Index) | Change in the severity of the functional dyspepsia index NDI (Nepean dyspepsia index) after 8 weeks from the start of the study therapy. The NDI questionnaire involves the patient's self-assessment of various manifestations of the disease and how much FD affects his life. The range of possible fluctuations in the total score of the Nepean dyspepsia index is from 10 to 50. The scale consists of 10 questions. Each section corresponds to 5 answer options (the lower score is 1, the highest is 5), reflecting the gradation of the severity of the symptom and coded according to the increase in the severity of the symptom or the loss of the ability to perform a certain task in the framework of daily activities. The minimum value is 10, the maximum value is 50. The higher score represents the worst outcome. | On baseline, after 4 and 8 weeks of the treatment | 
| Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale | The scale reflects the general well-being of a person, which is affected by the state of health, and consists of 11 questions. In the composition of the SF-36 dedicated 8 sections:1. Physical functioning,2. Role (physical) functioning 3. Pain.4. General health.5. Vitality.6. Social functioning.7. Emotional functioning. 8. Psychological health.The sections of the scale are combined into 2 total dimensions - the physical component of health (1-4 questions) and mental (5-8 questions). Subscales (questions 1-4) were summed to provide the information about the physical component, subscales (questions 5-8) - about the mental component. Each scale ranges from 0 to 100 so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. | On baseline and after 8 weeks of the treatment | 
| Percentage of Patients Terminating the Study Early | Percentage of patients terminating the study early due to lack of efficacy of the study therapy. Lack of efficacy of the study therapy is defined as retention or progression of the symptoms of functional dyspepsia resulting in prescription of the products for FD therapy (proton pump inhibitors, prokinetics, spasmolytics). | in 8 weeks of the treatment | 
| Indicators of Therapeutic and Side Effects, Efficacy Index on CGI-EI (Clinical Global Impression-Efficacy Index) Scale | Indicators of therapeutic and side effects, efficacy index on the scale of the general clinical impression CGI-EI (Clinical Global Impression Scale - Efficacy Index) after 8 weeks from the start of study therapy. Clinical Global Impression Efficacy Index (CGI-EI) will be filled by the investigator at the final Visit 5 (Week 8±3 days). Evaluation of the response to treatment should take into account both therapeutic efficacy and treatment-related side effects. Side effects value from 1 to 4. Therapeutic effect value as 0,4,8 or 12 points. The efficacy index is a sum. The minimum value is 1, the maximum value is 16. A lower score on the scales is the best outcome. | After 8 weeks of the treatment |