Trial Outcomes & Findings for Clinical Trial of Efficacy and Safety of Raphamin in the Treatment of Coronavirus Disease 2019 in Outpatients (NCT NCT05364671)

Last Updated: 2025-01-06

Results Overview

Severity of COVID-19 is assessed in accordance with criteria presented in the current edition of the clinical recommendations of the Ministry of Health of the Russian Federation "Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19)".

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

771 participants

Primary outcome timeframe

28 days

Results posted on

2025-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	Raphamin Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Overall Study STARTED	382	389
Overall Study COMPLETED	356	358
Overall Study NOT COMPLETED	26	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Raphamin Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Overall Study Negative PCR result for SARS-CoV-2	20	26
Overall Study Patient's inability or refusal to comply with protocol requirements	3	1
Overall Study Need to prescribe prohibited drugs in this study	1	3
Overall Study Patient's desire to complete the study early due to treatment failure or any other reason	2	0
Overall Study Deviation from the schedule of face-to-face visits on more than 1 day	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.	Total n=771 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=382 Participants	2 Participants n=389 Participants	5 Participants n=771 Participants
Age, Categorical Between 18 and 65 years	336 Participants n=382 Participants	352 Participants n=389 Participants	688 Participants n=771 Participants
Age, Categorical >=65 years	43 Participants n=382 Participants	35 Participants n=389 Participants	78 Participants n=771 Participants
Age, Continuous	43.3 years STANDARD_DEVIATION 15.3 • n=382 Participants	43.4 years STANDARD_DEVIATION 14.3 • n=389 Participants	43.4 years STANDARD_DEVIATION 14.8 • n=771 Participants
Sex: Female, Male Female	233 Participants n=382 Participants	249 Participants n=389 Participants	482 Participants n=771 Participants
Sex: Female, Male Male	149 Participants n=382 Participants	140 Participants n=389 Participants	289 Participants n=771 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	382 participants n=382 Participants	389 participants n=389 Participants	771 participants n=771 Participants

PRIMARY outcome

Timeframe: 28 days

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Number of Participants With COVID-19 Progression to a More Severe Form	59 Participants	89 Participants

SECONDARY outcome

Timeframe: 28 days

Sustained clinical recovery is a sustained improvement of clinical symptoms for at least 4 consecutive days. The day of improvement is considered the first of these 4 days. Criteria for improvement of clinical symptoms (according to the scoring system "Assessment of 14 Common COVID-19-Related Symptoms") are defined as follows: * a score of 1 or 0 (for stuffy or runny nose, sore throat, low energy or tiredness, muscle or body aches, headache, chills or shivering, feeling hot or feverish, nausea, diarrhea); * a score 0 (for shortness of breath/difficulty breathing and vomiting); * a score no more than 2 (for cough); * no new symptoms with a score of 1 or 0; * axillary temperature ≤37.3°С.

Outcome measures

Outcome measures
Measure	Raphamin n=381 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Time to Sustained Clinical Recovery After New Coronavirus Disease COVID-19.	4.5 day Standard Deviation 2.4	5.8 day Standard Deviation 4.7

SECONDARY outcome

Timeframe: 28 days

Based on the medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Percentage of Hospitalized Patients	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Severity of COVID-19 will be assessed in accordance with the criteria presented in the current edition of the clinical recommendations of the Ministry of Health of the Russian Federation "Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19)".

Outcome measures

Outcome measures
Measure	Raphamin n=59 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=89 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Time to COVID-19 Progression to a More Severe Form	1.6 day Standard Deviation 0.8	2.4 day Standard Deviation 3.9

OTHER_PRE_SPECIFIED outcome

Timeframe: On days 6 and 10

Population: In accordance with protocol only PCR positive participants were analyzed

Number of patients with a negative PCR test result for SARS-CoV-2 on days 6 and 10 of observation. Based on the medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=102 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=95 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Percentage of Patients With Negative PCR Test for SARS-CoV-2 Day 6	68 Participants	66 Participants
Percentage of Patients With Negative PCR Test for SARS-CoV-2 Day 10	93 Participants	89 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to day 6

The presence of adverse events. Based on medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Number of Participants With Adverse Events (AEs)	29 Participants	46 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to day 6

The intensity (severity) of adverse events. Based on medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=29 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=46 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Severity of AEs Mild	25 Number of AE	43 Number of AE
Severity of AEs Moderate	14 Number of AE	18 Number of AE
Severity of AEs Severe	2 Number of AE	0 Number of AE

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to day 6

The causal relationship to the study drug of adverse events. Based on medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=29 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=46 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Causal Relationship of AEs to the Sudy Drug Certain	0 Number of AEs	1 Number of AEs
Causal Relationship of AEs to the Sudy Drug Probable	1 Number of AEs	0 Number of AEs
Causal Relationship of AEs to the Sudy Drug Possible	1 Number of AEs	2 Number of AEs
Causal Relationship of AEs to the Sudy Drug Doubtful	0 Number of AEs	6 Number of AEs
Causal Relationship of AEs to the Sudy Drug No relation	39 Number of AEs	52 Number of AEs

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to day 6

The outcome of adverse events. Based on medical records.

Outcome measures

Outcome measures
Measure	Raphamin n=29 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=46 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Outcome of AEs Recovery/resolution	23 Number of AEs	40 Number of AEs
Outcome of AEs Incomplete recovery/ resolution	5 Number of AEs	6 Number of AEs
Outcome of AEs No recovery/resolution	1 Number of AEs	0 Number of AEs
Outcome of AEs Unknown	12 Number of AEs	15 Number of AEs

OTHER_PRE_SPECIFIED outcome

Timeframe: On Visit 1 (day 1), Visit 3 (day 6), Visit 4 (day10)

The outcome measure is based on the medical records. The patient's heart rate (heart rate) is measured by the physician in visits 1, 3 and 4 (on days 1 and 6).

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm) Visit 1	81.7 Bpm Standard Deviation 10.4	81.9 Bpm Standard Deviation 10.5
Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm) Visit 3	73.9 Bpm Standard Deviation 6.3	74.4 Bpm Standard Deviation 6.4
Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm) Visit 4	72.6 Bpm Standard Deviation 6.0	73.2 Bpm Standard Deviation 5.8

OTHER_PRE_SPECIFIED outcome

Timeframe: On Visit 1 (day 1), Visit 3 (day 6), Visit 4 (day10)

Outcome Measure is based on the medical records. The patient's respiration rate (breathing rate) is measured by physician in visits 1, 3 and 4 (on days 1 and 6).

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute Visit 1	17.1 Breaths per minute Standard Deviation 1.4	17.2 Breaths per minute Standard Deviation 1.5
Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute Visit 3	16.6 Breaths per minute Standard Deviation 1.2	16.5 Breaths per minute Standard Deviation 1.4
Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute Visit 4	16.4 Breaths per minute Standard Deviation 1.3	16.4 Breaths per minute Standard Deviation 1.3

OTHER_PRE_SPECIFIED outcome

Timeframe: On Visit 1 (day 1), Visit 3 (day 6), Visit 4 (day10)

Outcome Measure is based on the medical records. The patient's capillary blood oxygen saturation (SpO2) is measured by physician in visits 1, 3 and 4 (on days 1 and 6).

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Changes in Vital Signs: Capillary Blood Oxygen Saturation (SpO2) Visit 1	97.8 percentage of oxygen Standard Deviation 0.9	97.8 percentage of oxygen Standard Deviation 0.8
Changes in Vital Signs: Capillary Blood Oxygen Saturation (SpO2) Visit 3	98.3 percentage of oxygen Standard Deviation 0.8	98.3 percentage of oxygen Standard Deviation 0.8
Changes in Vital Signs: Capillary Blood Oxygen Saturation (SpO2) Visit 4	98.4 percentage of oxygen Standard Deviation 0.8	98.5 percentage of oxygen Standard Deviation 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: On Visit 1 (day 1), Visit 3 (day 6), Visit 4 (day10)

Outcome Measure is based on the medical records. The patient's blood pressure is measured by the physician in visits 1, 3 and 4 (on days 1 and 6).

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) SBP/Visit 1	122.1 mmHg Standard Deviation 9.5	122.1 mmHg Standard Deviation 9.9
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) SBP/Visit 3	121.8 mmHg Standard Deviation 8.3	121.2 mmHg Standard Deviation 8.2
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) SBP/Visit 4	121.1 mmHg Standard Deviation 7.6	121.2 mmHg Standard Deviation 7.9
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) DBP/Visit 1	76.9 mmHg Standard Deviation 6.8	76.8 mmHg Standard Deviation 7.4
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) DBP/Visit 3	76.5 mmHg Standard Deviation 6.2	76.3 mmHg Standard Deviation 6.2
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg) DBP/Visit 4	76.2 mmHg Standard Deviation 6.0	76.1 mmHg Standard Deviation 6.3

OTHER_PRE_SPECIFIED outcome

Timeframe: On Visit 1 (day 1) and Visit 3 (day 6)

Measure is based on the Hematology, blood chemistry, and urinalysis parameters, which are beyond the reference values at the end of treatment.

Outcome measures

Outcome measures
Measure	Raphamin n=382 Participants Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 Participants Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Percentage of Patients With Clinically Significant Abnormal Laboratory Tests	13 Participants	16 Participants

Adverse Events

Raphamin

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Raphamin n=382 participants at risk Tablet for oral use. Raphamin: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. On the first day, 8 tablets should be administered using the following regimen: 1 tablet every 30 minutes in the first 2 hours (5 tablets in total within 2 hours), then additionally one tablet 3 times with regular time intervals. From day 2 onwards, 1 tablet taken 3 times daily. The treatment period is 5 days.	Placebo n=389 participants at risk Tablet for oral use. Placebo: Tablet for oral use. The drug is administered not during meals. The tablet should be held in mouth until complete dissolution. Placebo is administered according to the Raphamin regimen.
Cardiac disorders Worsening of atrial fibrillation	0.26% 1/382 • Number of events 1 • Registration of AEs begins after the first dose of study drug and continues throughout the entire period of study therapy - 28 days.	0.00% 0/389 • Registration of AEs begins after the first dose of study drug and continues throughout the entire period of study therapy - 28 days.
Injury, poisoning and procedural complications Complicated fracture	0.26% 1/382 • Number of events 1 • Registration of AEs begins after the first dose of study drug and continues throughout the entire period of study therapy - 28 days.	0.00% 0/389 • Registration of AEs begins after the first dose of study drug and continues throughout the entire period of study therapy - 28 days.

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