Trial Outcomes & Findings for Сlinical Trial of Efficacy and Safety of Prospekta in the Treatment of Post-COVID-19 Asthenia. (NCT NCT05074888)

Last Updated: 2024-09-23

Results Overview

Fatigue Severity Scale (FSS). Change in the mean FSS score after 4 weeks of treatment. The total score of the scale, which consists of 9 questions, varies between 9-63. This scale consists of a 7-point Likert scale. 1 point means strongly disagree, 7 means strongly agree. People are asked to mark the appropriate options for each question taking into account their status in the last 1 month period. A total of 36 points and above indicate fatigue. A higher score is indicated high level of fatigue.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

676 participants

Primary outcome timeframe

after 4 weeks of treatment

Results posted on

2024-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	Prospekta Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Overall Study STARTED	330	346
Overall Study COMPLETED	330	346
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	Prospekta n=330 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.	Total n=676 Participants Total of all reporting groups
Age, Continuous	44.3 years STANDARD_DEVIATION 12.5 • n=330 Participants	42.8 years STANDARD_DEVIATION 12.6 • n=346 Participants	43.5 years STANDARD_DEVIATION 12.6 • n=676 Participants
Sex: Female, Male Female	216 Participants n=330 Participants	236 Participants n=346 Participants	452 Participants n=676 Participants
Sex: Female, Male Male	114 Participants n=330 Participants	110 Participants n=346 Participants	224 Participants n=676 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	330 participants n=330 Participants	346 participants n=346 Participants	676 participants n=676 Participants

PRIMARY outcome

Timeframe: after 4 weeks of treatment

Population: Six patients were excluded from the trial before 4 week therefore no data was collected on 4 weeks timepoint (3 patients from Prospekta group and 3 patients from Placebo group).

Outcome measures

Outcome measures
Measure	Prospekta n=327 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Mean FSS Score. After 4 weeks	29.9 score on a scale Standard Deviation 9.2	31.9 score on a scale Standard Deviation 9.9
Change in the Mean FSS Score. Baseline	46.4 score on a scale Standard Deviation 6.9	45.9 score on a scale Standard Deviation 6.6
Change in the Mean FSS Score. ∆ between baseline and 4 weeks later	16.5 score on a scale Standard Deviation 9.5	14.0 score on a scale Standard Deviation 9.4

SECONDARY outcome

Timeframe: after 4 weeks of treatment

Change in distance when performing the 6-minute walk test after 4 weeks of treatment. The test is carried out with the aim of objectively assessing the patient's physical tolerance. The patient should walk the maximum possible distance for himself at his own pace on a flat surface in 6 minutes.

Outcome measures

Outcome measures
Measure	Prospekta n=328 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in Distance of the 6-minute Walk Test. Baseline	426.4 meters Standard Deviation 119.2	416.9 meters Standard Deviation 112.8
Change in Distance of the 6-minute Walk Test. After 4 weeks	457.8 meters Standard Deviation 118.2	444.7 meters Standard Deviation 110.7
Change in Distance of the 6-minute Walk Test. ∆ between baseline and 4 weeks later	31.4 meters Standard Deviation 44.5	27.8 meters Standard Deviation 38.1

SECONDARY outcome

Timeframe: after 4 weeks of treatment

Hospital Anxiety and Depression Scale (HADS). Change in the severity of anxiety and depression on the HADS subscales after 4 weeks of treatment. The scale is composed of 14 statements serving 2 subscales: "anxiety" (odd items - 1, 3, 5, 7, 9, 11, 13) and "depression" (even items - 2, 4, 6, 8, 10, 12 , 14). Each statement corresponds to 4 answer options, reflecting the gradation of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values: 0-7 - "norm" (absence of reliably expressed symptoms of anxiety and depression); 8-10 - "subclinical anxiety / depression"; 11 and above - "clinical anxiety / depression". The anxiety subscale ranges from 0 to 21, with higher values reflecting a worse outcome.

Outcome measures

Outcome measures
Measure	Prospekta n=326 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Severity of Anxiety on the HADS Subscale. Baseline	8.5 score on a scale Standard Deviation 4.1	8.8 score on a scale Standard Deviation 3.9
Change in the Severity of Anxiety on the HADS Subscale. After 4 weeks	5.5 score on a scale Standard Deviation 3.2	6.0 score on a scale Standard Deviation 3.3
Change in the Severity of Anxiety on the HADS Subscale. ∆ between baseline and 4 weeks later	3.0 score on a scale Standard Deviation 3.2	2.8 score on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: after 4 weeks of treatment

Hospital Anxiety and Depression Scale (HADS). Change in the severity of depression on the HADS subscale after 4 weeks of treatment. The scale is composed of 14 statements serving 2 subscales: "anxiety" (odd items - 1, 3, 5, 7, 9, 11, 13) and "depression" (even items - 2, 4, 6, 8, 10, 12 , 14). Each statement corresponds to 4 answer options, reflecting the gradation of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values: 0-7 - "norm" (absence of reliably expressed symptoms of anxiety and depression); 8-10 - "subclinical anxiety / depression"; 11 and above - "clinical anxiety / depression". The depression subscale ranges from 0 to 21, with higher values reflecting a worse outcome.

Outcome measures

Outcome measures
Measure	Prospekta n=327 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Severity of Depression on the HADS Subscale. Baseline	8.1 score on a scale Standard Deviation 3.7	8.3 score on a scale Standard Deviation 3.8
Change in the Severity of Depression on the HADS Subscale. After 4 weeks	4.7 score on a scale Standard Deviation 2.9	5.2 score on a scale Standard Deviation 3.0
Change in the Severity of Depression on the HADS Subscale. ∆ between baseline and 4 weeks later	3.4 score on a scale Standard Deviation 3.0	3.1 score on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: after 4 weeks of treatment and after 4 weeks of follow-up at week 8

Population: One patient in Prospekta group was excluded from the trial before finishing follow-up period therefore no data was collected within 4 weeks of follow-up.

Change in mean FSS score over 4 weeks of follow-up period at the end of treatment. The total score of the scale, which consists of 9 questions, varies between 9-63. This scale consists of a 7-point Likert scale. 1 point means strongly disagree, 7 means strongly agree. People are asked to mark the appropriate options for each question taking into account their status in the last 1 month period. A total of 36 points and above indicate fatigue. A higher score is indicated high level of fatigue.

Outcome measures

Outcome measures
Measure	Prospekta n=327 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Mean FSS Score Within Follow-up Period. ∆ between value after 4 weeks and after 8 weeks	7.1 score on a scale Standard Deviation 6.3	7.0 score on a scale Standard Deviation 6.9
Change in the Mean FSS Score Within Follow-up Period. After 4 weeks	29.9 score on a scale Standard Deviation 9.2	31.9 score on a scale Standard Deviation 9.9
Change in the Mean FSS Score Within Follow-up Period. After 8 weeks	22.9 score on a scale Standard Deviation 9.0	25.0 score on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: after 4 weeks of treatment and after 4 weeks of follow-up at week 8

Population: One patient in Prospekta group and three patients in Placebo group were excluded from the trial before finishing follow-up period therefore no data was collected within 4 weeks of follow-up.

Change in distance when performing the 6-minute walk test over a 4-week follow-up period at the end of treatment. The test is carried out with the aim of objectively assessing the patient's physical tolerance. The patient should walk the maximum possible distance for himself at his own pace on a flat surface in 6 minutes.

Outcome measures

Outcome measures
Measure	Prospekta n=328 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in Distance of the 6-minute Walk Test Within Follow-up Period. After 4 weeks	457.8 meter Standard Deviation 118.2	444.7 meter Standard Deviation 110.7
Change in Distance of the 6-minute Walk Test Within Follow-up Period. After 8 weeks	472.9 meter Standard Deviation 116.5	462.7 meter Standard Deviation 110.1
Change in Distance of the 6-minute Walk Test Within Follow-up Period. ∆ between value after 4 weeks and after 8 weeks	15.9 meter Standard Deviation 32.1	18.8 meter Standard Deviation 32.0

SECONDARY outcome

Timeframe: after 4 weeks of treatment and after 4 weeks of follow-up at week 8

Change in the severity of anxiety on the HADS subscales over a 4-week follow-up period at the end of treatment. The scale is composed of 14 statements serving 2 subscales: "anxiety" (odd items - 1, 3, 5, 7, 9, 11, 13) and "depression" (even items - 2, 4, 6, 8, 10, 12 , 14). Each statement corresponds to 4 answer options, reflecting the gradation of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values: 0-7 - "norm" (absence of reliably expressed symptoms of anxiety and depression); 8-10 - "subclinical anxiety / depression"; 11 and above - "clinical anxiety / depression". The anxiety subscale ranges from 0 to 21, with higher values reflecting a worse outcome.

Outcome measures

Outcome measures
Measure	Prospekta n=327 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Severity of Anxiety on the HADS Subscales Within Follow-up Period. After 4 weeks	5.5 score on a scale Standard Deviation 3.2	6.0 score on a scale Standard Deviation 3.3
Change in the Severity of Anxiety on the HADS Subscales Within Follow-up Period. After 8 weeks	4.0 score on a scale Standard Deviation 2.8	4.4 score on a scale Standard Deviation 3.0
Change in the Severity of Anxiety on the HADS Subscales Within Follow-up Period. ∆ between value after 4 weeks and after 8 weeks	1.5 score on a scale Standard Deviation 2.3	1.6 score on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: after 4 weeks of treatment and after 4 weeks of follow-up at week 8

Change in the severity of depression on the HADS subscales over a 4-week follow-up period at the end of treatment. The scale is composed of 14 statements serving 2 subscales: "anxiety" (odd items - 1, 3, 5, 7, 9, 11, 13) and "depression" (even items - 2, 4, 6, 8, 10, 12 , 14). Each statement corresponds to 4 answer options, reflecting the gradation of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values: 0-7 - "norm" (absence of reliably expressed symptoms of anxiety and depression); 8-10 - "subclinical anxiety / depression"; 11 and above - "clinical anxiety / depression". The depression subscale ranges from 0 to 21, with higher values reflecting a worse outcome.

Outcome measures

Outcome measures
Measure	Prospekta n=327 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=343 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Change in the Severity of Depression on the HADS Subscales Within Follow-up Period. After 4 weeks	4.7 score on a scale Standard Deviation 2.9	5.2 score on a scale Standard Deviation 3.0
Change in the Severity of Depression on the HADS Subscales Within Follow-up Period. After 8 weeks	3.4 score on a scale Standard Deviation 2.6	3.7 score on a scale Standard Deviation 2.8
Change in the Severity of Depression on the HADS Subscales Within Follow-up Period. ∆ between value after 4 weeks and after 8 weeks	1.4 score on a scale Standard Deviation 2.1	1.5 score on a scale Standard Deviation 2.1

SECONDARY outcome

Timeframe: after 4 weeks of treatment and within 4 weeks of the follow-up period at the end of the treatment.

Population: Lower patient count is due to missing data on visits 2 and 3.

Based on medical records. Vital signs will be measured in a medical setting.

Outcome measures

Outcome measures
Measure	Prospekta n=330 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Changes in Vital Signs (Pulse Rate (Heart Rate)). Visit 1: baseline	73.0 beats per minute Standard Deviation 6.9	73.4 beats per minute Standard Deviation 6.9
Changes in Vital Signs (Pulse Rate (Heart Rate)). Visit 2: after 4 weeks of treatment	71.8 beats per minute Standard Deviation 5.8	71.9 beats per minute Standard Deviation 5.6
Changes in Vital Signs (Pulse Rate (Heart Rate)). Visit 3: after 4 weeks of follow-up at week 8	71.6 beats per minute Standard Deviation 5.3	71.4 beats per minute Standard Deviation 5.5

SECONDARY outcome

Timeframe: after 4 weeks of treatment and within 4 weeks of the follow-up period at the end of the treatment (Visit 1: baseline, Visit 2: after 4 weeks of treatment, and Visit 3: after 4 weeks of follow-up at week 8)

Population: Lower patient count is due to missing data on visits 2 and 3.

Based on medical records. Vital signs will be measured in a medical setting.

Outcome measures

Outcome measures
Measure	Prospekta n=330 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Changes in Vital Signs (Respiration Rate (Breathing Rate)). Visit 1	16.3 breaths per minute Standard Deviation 1.3	16.4 breaths per minute Standard Deviation 1.3
Changes in Vital Signs (Respiration Rate (Breathing Rate)). Visit 2	16.2 breaths per minute Standard Deviation 1.2	16.2 breaths per minute Standard Deviation 1.2
Changes in Vital Signs (Respiration Rate (Breathing Rate)). Visit 3	16.2 breaths per minute Standard Deviation 1.2	16.2 breaths per minute Standard Deviation 1.2

SECONDARY outcome

Population: Lower patient count is due to missing data on visits 2 and 3.

Based on medical records. Vital signs will be measured in a medical setting.

Outcome measures

Outcome measures
Measure	Prospekta n=330 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Changes in Vital Signs (Blood Pressure). SBP/Visit 1	121.3 mmHg Standard Deviation 8.6	120.9 mmHg Standard Deviation 8.3
Changes in Vital Signs (Blood Pressure). SBP/Visit 2	121.1 mmHg Standard Deviation 8.4	120.6 mmHg Standard Deviation 8.1
Changes in Vital Signs (Blood Pressure). SBP/Visit 3	121.1 mmHg Standard Deviation 8.2	120.4 mmHg Standard Deviation 7.4
Changes in Vital Signs (Blood Pressure). DBP/Visit 1	75.8 mmHg Standard Deviation 6.5	75.8 mmHg Standard Deviation 6.5
Changes in Vital Signs (Blood Pressure). DBP/Visit 2	75.8 mmHg Standard Deviation 6.3	75.9 mmHg Standard Deviation 6.3
Changes in Vital Signs (Blood Pressure). DBP/Visit 3	76.0 mmHg Standard Deviation 6.1	75.4 mmHg Standard Deviation 5.9

SECONDARY outcome

Timeframe: 8 weeks

The number of participants with adverse events (AEs). Based on medical records.

Outcome measures

Outcome measures
Measure	Prospekta n=330 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Presence of Adverse Events (AEs).	20 Participants	20 Participants

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Outcome measures
Measure	Prospekta n=20 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=20 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
The Severity of AEs. Mild	13 number of AEs	15 number of AEs
The Severity of AEs. Moderate	11 number of AEs	13 number of AEs

SECONDARY outcome

Timeframe: 8 weeks

The outcome of adverse events. Based on medical records.

Outcome measures

Outcome measures
Measure	Prospekta n=20 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=20 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
The Outcome of AEs. Recovery/resolution	22 number of AEs	26 number of AEs
The Outcome of AEs. No recovery/resolution	2 number of AEs	0 number of AEs
The Outcome of AEs. Unknown	0 number of AEs	2 number of AEs

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Outcome measures
Measure	Prospekta n=20 Participants Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=20 Participants Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
AEs Causal Relationship to the Study Drug. Possible	1 number of AEs	0 number of AEs
AEs Causal Relationship to the Study Drug. Doubtful	0 number of AEs	9 number of AEs
AEs Causal Relationship to the Study Drug. No relation	20 number of AEs	15 number of AEs
AEs Causal Relationship to the Study Drug. Probable	3 number of AEs	4 number of AEs

Adverse Events

Prospekta

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 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	Prospekta n=330 participants at risk Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. Prospekta: Oral administration.	Placebo n=346 participants at risk Tablet for oral use. Placebo using Prospekta scheme. Placebo: Oral administration.
Gastrointestinal disorders Abdominal pain	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Epigastric pain	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Diarrhea	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Epigastric discomfort	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Stomach cramps	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Dry mouth	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Gastrointestinal disorders Nausea	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Viral infection of the respiratory tract	0.61% 2/330 • Number of events 2 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Herpes	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Laboratory confirmed coronavirus infection COVID-19	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.58% 2/346 • Number of events 2 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Acute respiratory tract infection	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Acute rhinitis	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Infections and infestations Rhinitis	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Investigations BP above normal	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Immune system disorders Food allergy	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Musculoskeletal and connective tissue disorders Lumbar spine pain	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Musculoskeletal and connective tissue disorders Back pain	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Musculoskeletal and connective tissue disorders Dorsopathy	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Headache	0.91% 3/330 • Number of events 3 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	1.2% 4/346 • Number of events 4 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Dizziness	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.87% 3/346 • Number of events 3 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Root lumbar pain	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Upper limb numbness	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Sensory disorder	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Drowsiness	0.61% 2/330 • Number of events 2 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Nervous system disorders Cephalalgia	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Reproductive system and breast disorders Ovarian hemorrhage	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Vascular disorders Hypertensive crisis	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Vascular disorders Worsening of hypertension	0.61% 2/330 • Number of events 2 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
General disorders Flu-like symptoms	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
General disorders Precardial pain	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
General disorders Mucosal dryness	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Product Issues Residual taste after drug administration	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Psychiatric disorders Insomnia	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Psychiatric disorders Nightmares	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Psychiatric disorders Tearfulness	0.30% 1/330 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.00% 0/346 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.
Injury, poisoning and procedural complications Back contusion	0.00% 0/330 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.	0.29% 1/346 • Number of events 1 • Reporting of AEs begins after the first dose of IP, continues throughout the study treatment period, and for 4 weeks after the last dose of IP during the follow-up period, up to 8 weeks.