Trial Outcomes & Findings for Clinical Trial of Efficacy and Safety of Kolofort in Functional Dyspepsia Patients (NCT NCT03119766)

NCT ID: NCT03119766

Last Updated: 2022-06-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

370 participants

Primary outcome timeframe

On baseline, after 4 and 8 weeks of the treatment

Results posted on

2022-06-07

Participant Flow

A total of 370 patients were enrolled in the study and signed informed consent. After undergoing screening procedures, 61 patients were excluded by the investigators because they did not meet the inclusion criteria, or they had non-inclusion criteria. 309 patients were randomized into two groups - 151 into Kolofort group and 158 into Placebo group.

Participant milestones

Participant milestones
Measure	Kolofort 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. Kolofort: Oral administration	Placebo 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. Placebo: Oral administration
Overall Study STARTED	151	158
Overall Study COMPLETED	151	158
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration	Total n=309 Participants Total of all reporting groups
Age, Continuous	30.5 years STANDARD_DEVIATION 7.7 • n=151 Participants	29.7 years STANDARD_DEVIATION 7.9 • n=158 Participants	30.1 years STANDARD_DEVIATION 7.8 • n=309 Participants
Sex: Female, Male Female	105 Participants n=151 Participants	110 Participants n=158 Participants	215 Participants n=309 Participants
Sex: Female, Male Male	46 Participants n=151 Participants	48 Participants n=158 Participants	94 Participants n=309 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	151 participants n=151 Participants	158 participants n=158 Participants	309 participants n=309 Participants

PRIMARY outcome

Timeframe: On baseline, after 4 and 8 weeks of the treatment

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Changes in Severity of Functional Dyspepsia Symptoms Baseline score	10.1 score on a scale Standard Deviation 3.1	10.0 score on a scale Standard Deviation 3.9
Changes in Severity of Functional Dyspepsia Symptoms Score after 4 weeks	5.1 score on a scale Standard Deviation 3.0	5.2 score on a scale Standard Deviation 3.0
Changes in Severity of Functional Dyspepsia Symptoms Score after 8 weeks	2.9 score on a scale Standard Deviation 2.5	3.7 score on a scale Standard Deviation 3.6
Changes in Severity of Functional Dyspepsia Symptoms "Baseline minus 8 weeks" score difference	7.2 score on a scale Standard Deviation 3.3	6.3 score on a scale Standard Deviation 4.6

SECONDARY outcome

Timeframe: After 8 weeks of the treatment

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).

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Percentage of Patients With a Decrease in the Severity of FD Symptoms Reduction ≥ 5 points	121 Participants	114 Participants
Percentage of Patients With a Decrease in the Severity of FD Symptoms Reduction ≥ 1 point	150 Participants	151 Participants
Percentage of Patients With a Decrease in the Severity of FD Symptoms Reduction ≥ 2 points	145 Participants	141 Participants
Percentage of Patients With a Decrease in the Severity of FD Symptoms Reduction ≥ 3 points	138 Participants	134 Participants
Percentage of Patients With a Decrease in the Severity of FD Symptoms Reduction ≥ 4 points	133 Participants	125 Participants

SECONDARY outcome

Timeframe: On baseline, after 4 and 8 weeks of the treatment

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.

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Change in the Severity of the Functional Dyspepsia Index NDI (Nepean Dyspepsia Index) Baseline	23.5 units on a scale Standard Deviation 7.0	23.5 units on a scale Standard Deviation 6.9
Change in the Severity of the Functional Dyspepsia Index NDI (Nepean Dyspepsia Index) After 4 weeks	17.1 units on a scale Standard Deviation 5.6	17.0 units on a scale Standard Deviation 6.0
Change in the Severity of the Functional Dyspepsia Index NDI (Nepean Dyspepsia Index) After 8 weeks	14.4 units on a scale Standard Deviation 5.1	14.9 units on a scale Standard Deviation 6.0
Change in the Severity of the Functional Dyspepsia Index NDI (Nepean Dyspepsia Index) "Baseline minus 8 weeks" score difference	9.1 units on a scale Standard Deviation 7.1	8.5 units on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: On baseline and after 8 weeks of the treatment

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.

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale Baseline (physical score)	49.9 score on a scale Standard Deviation 7.8	49.4 score on a scale Standard Deviation 7.7
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale After 8 weeks (physical score)	56.3 score on a scale Standard Deviation 6.5	56.2 score on a scale Standard Deviation 6.3
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale "Baseline minus 8 weeks" score difference (physical score)	6.4 score on a scale Standard Deviation 7.5	6.8 score on a scale Standard Deviation 7.0
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale Baseline (mental score)	33.6 score on a scale Standard Deviation 5.7	34.0 score on a scale Standard Deviation 6.1
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale After 8 weeks (mental score)	37.1 score on a scale Standard Deviation 4.5	36.9 score on a scale Standard Deviation 4.9
Changes in the Quality of Life of Patients on the SF-36 (Short Form-36) Health Survey Scale "Baseline minus 8 weeks" score difference (mental score)	3.5 score on a scale Standard Deviation 6.3	2.9 score on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: in 8 weeks of the treatment

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).

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Percentage of Patients Terminating the Study Early	0 Participants	1 Participants

SECONDARY outcome

Timeframe: After 8 weeks of the treatment

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.

Outcome measures

Outcome measures
Measure	Kolofort n=151 Participants 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. Kolofort: Oral administration	Placebo n=158 Participants 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. Placebo: Oral administration
Indicators of Therapeutic and Side Effects, Efficacy Index on CGI-EI (Clinical Global Impression-Efficacy Index) Scale Side effects	1.09 units on a scale Standard Deviation 0.31	1.04 units on a scale Standard Deviation 0.19
Indicators of Therapeutic and Side Effects, Efficacy Index on CGI-EI (Clinical Global Impression-Efficacy Index) Scale Therapeutic effect	2.67 units on a scale Standard Deviation 2.96	3.33 units on a scale Standard Deviation 3.49
Indicators of Therapeutic and Side Effects, Efficacy Index on CGI-EI (Clinical Global Impression-Efficacy Index) Scale Efficacy index	3.76 units on a scale Standard Deviation 2.98	4.37 units on a scale Standard Deviation 3.51

Adverse Events

Kolofort

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Mikhail Putilovskiy, MD, PhD, Clinical and Medical Department Director

MATERIA MEDICA HOLDING

Phone: +74952761571

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Kolofort n=151 participants at risk 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. Kolofort: Oral administration	Placebo n=158 participants at risk 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. Placebo: Oral administration
Gastrointestinal disorders Hyperkinesia gastrointestinal intestinal tract	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Gastrointestinal disorders Diarrhea	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Gastrointestinal disorders Dyspepsia	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Gastrointestinal disorders Constipation	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	1.3% 2/158 • Number of events 2 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Gastrointestinal disorders Dry mouth	1.3% 2/151 • Number of events 2 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Gastrointestinal disorders Nausea	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Infections and infestations ARVI	1.3% 2/151 • Number of events 2 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Infections and infestations Nasopharyngitis	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Infections and infestations Rhinitis	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Infections and infestations Tonsillitis	0.00% 0/151 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Infections and infestations Cystitis	0.00% 0/151 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Respiratory, thoracic and mediastinal disorders Sore throat	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Respiratory, thoracic and mediastinal disorders Vasomotor rhinitis	0.00% 0/151 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Nervous system disorders Headache	1.3% 2/151 • Number of events 2 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	1.3% 2/158 • Number of events 2 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Nervous system disorders Dizziness	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Vascular disorders Hypertension	0.00% 0/151 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
General disorders Asthenia	0.66% 1/151 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.00% 0/158 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
Surgical and medical procedures Tooth extraction	0.00% 0/151 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).	0.63% 1/158 • Number of events 1 • During the treatment period - 8 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).