Study of M5049 in Participants With COVID-19 Pneumonia (ANEMONE)

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04448756
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 149
• Locations: 21
• Arms: 3
• Actual Duration (Months): 12.6
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The study will evaluate the safety and efficacy of orally-administered M5049 in Coronavirus disease 2019 (COVID-19) pneumonia participants who are hospitalized but not on mechanical ventilation.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Disease 2019	Drug: M5049; Drug: M5049; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia (ANEMONE)
• Actual Study Start Date: Jul 29, 2020
• Actual Primary Completion Date: Aug 16, 2021
• Actual Study Completion Date: Aug 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: M5049 50 mg	Drug: M5049; Participants received M5049 50 milligram (mg) orally twice daily for 14 days.
Experimental: M5049 100 mg	Drug: M5049; Participants received M5049 100 mg orally twice daily for 14 days.
Placebo Comparator: Placebo	Drug: Placebo; Participants received placebo tablets matched to M5049 daily for 14 days.

Outcome Measures

Primary Outcome Measures

1. Time to Recovery [Day 1 through Day 28]

   Time to recovery was defined as the time from first dose (Day 1) to first occurrence of World Health Organization (WHO) 9-point ordinal scale 3 or less. The scoring is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or Extracorporeal membrane oxygenation (ECMO); 8. Death.

2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious TEAEs (SAEs) According to NCI-CTCAE Version 5.0 [Day 1 through Day 60]

   Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs.

3. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters [Day 1 through Day 28]

   Laboratory investigation included hematology and biochemistry. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.

4. Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements [Day 1 through Day 28]

   12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.

Secondary Outcome Measures

1. Percentage of Participants Alive and Not Requiring Supplemental Oxygenation [Day 3, Day 7, Day 14, Day 21 and Day 28]

   The percentage of participants who were alive and did not require supplemental oxygenation or ventilatory support (including noninvasive or mechanical ventilation and Extra Corporeal Membrane Oxygenation [ECMO]) reported.

2. Number of Participants in Each Clinical Status Category Based on 9-Point Ordinal Scale [Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60]

   Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or ECMO; 8. Death.

3. Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours in Room Air [Day 1 through Day 28]

   SpO2 is an estimate of the amount of oxygen in the blood. It is the percentage of hemoglobin containing oxygen compared to the total amount of hemoglobin in the blood (that is, oxygenated hemoglobin versus oxygenated and non-oxygenated hemoglobin). SpO2 measured by pulse oximetry. The time to SPO2 greater than or equal to (>=) 94 percent (%) sustained for at least 24 hours in room air is reported in days.

4. Percentage of Participants With All-Cause Mortality [Day 1 through Day 60]

   Percentage of Participants who died for any reason reported.

5. Time to Intensive Care Unit (ICU) Admission [Day 1 through Day 28]

   Time to ICU admission was defined as the time from first dose (Day 1) to the date/time of ICU admission, or death, whichever occurs first, in days. Event-free survival function for time to event (ICU admission or death) estimated via Kaplan-Meier method.

6. Time to Non-Invasive Mechanical Ventilation [Day 1 through Day 28]

   Time to non-invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status >= 5, in days. Event-free survival function for time to event (Non-invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death

7. Time to Invasive Mechanical Ventilation [Day 1 through Day 28]

   Time to invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status >= 6, in days. Event-free survival function for time to event (invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death.

8. Total Length of Stay in Intensive Care Unit (ICU) [Day 1 through Day 60]

   Total days in the ICU was defined as the sum, for all ICU admissions, of the time from ICU admission to the date of ICU discharge, in days.

9. Total Length of Hospitalization Stay [Day 1 through Day 60]

   Total days in the hospital was defined as the sum, for all hospitalization events, of the time from first dose to the date of hospital discharge in days.

10. Time to Hospital Discharge [Day 1 through Day 60]

    The time to hospital discharge, defined as the time from first dose (Day 1) to the date of first hospitalization discharge, in days.

11. Percent Change From Baseline in Inflammatory Biomarkers Over Time [Baseline, Day 3, Day7, Day 10, Day 14 and Day 28]

    C-Reactive Protein, D-Dimer and Ferritin inflammatory biomarkers were analyzed for this study. Percent Change From Baseline in Inflammatory Biomarkers Over Time were reported here.

12. Percent Change From Baseline in Serum Cytokine Biomarkers [Baseline, Day 3, Day7, Day 14 and Day 28]

    Interleukin 6 and Interleukin 8 serum cytokine biomarkers were analyzed. Percent Change From Baseline in Serum Cytokine Biomarkers were reported.

13. Percentage of Participants With Relapse [Day 5 through Day 60]

    Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.

14. Percentage of Participants Who Are Re-Hospitalized [Day 5 through Day 60]

    Percentage or participants who are re-hospitalized due to coronavirus disease 2019 (Covid-19) complications were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant provides signed informed consent prior to the initiation of any study assessments

• Has laboratory-confirmed SARS-CoV-2 Infection as determined by nucleic acid amplification test, polymerase chain reaction, antigen test or other commercial or public health assay (based on locally acceptable accepted guidelines) in a sample collected less than (<)10 days prior to randomization

• Has chest imaging consistent with COVID-19 pneumonia (as per locally accepted guidelines) If chest imaging is not available during Screening, please discuss with Medical Monitor or designee regarding evidence of probable COVID-19 pneumonia for study participant eligibility

• Not on mechanical ventilation or ECMO

• Has an SpO2 less than (<) 94 percent in room air And able to maintain a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) greater than or equal to (>=) 150 (Or equivalent SpO2/FiO2 >=190) with a maximum FiO2 0.4 if participant is on chronic low oxygen therapy (less than or equal to 2 Liter), assess their current baseline oxygen requirements for eligibility

• Requires hospitalization

• Other protocol defined inclusion criteria may apply

Exclusion Criteria:

• Any condition that could interfere with the study objectives, conduct or evaluation in the opinion of the Investigator or Sponsor or designee

• Significantly uncontrolled medical illness (eg, cardiovascular disease, hypertension, diabetes mellitus, obstructive lung disease, neurological associated with seizures (example: cerebrovascular accident/stroke, acute brain infection, traumatic brain injury, progressive brain disease, congenital brain disease or neuropsychiatric disorder)

• Known active infection other than COVID-19

• Pregnancy or Breastfeeding

• Other protocol defined exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LAC-USC Medical Center	Los Angeles	California	United States	90033
2	Sharp Chula Vista Medical Center	San Diego	California	United States	92123
3	Henry Ford Medical Center	Detroit	Michigan	United States	48202
4	Holy Name Hospital - Dept of Multiple Sclerosis Comp Care Center	Teaneck	New Jersey	United States	07666
5	Christus Spohn Hospital Corpus Christi-Memorial	Corpus Christi	Texas	United States	78404
6	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte		Brazil
7	Hospital Dia do Pulmão	Blumenau		Brazil
8	Hospital São José - Sociedade Literária e Caritativa Santo Agostinho	Criciúma		Brazil
9	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil
10	HMCG - Hospital e Maternidade Dr. Christovão da Gama	Santo André		Brazil
11	Pesquisare	Santo André		Brazil
12	Hospital Leforte Morumbi	Sao Paulo		Brazil
13	Hospital Alemão Oswaldo Cruz	São Paulo		Brazil
14	Hospital Bandeirantes / Hospital Leforte Liberdade	São Paulo		Brazil
15	Instituto de Infectologia Emílio Ribas	São Paulo		Brazil
16	Manila Doctors Hospital	Manila		Philippines
17	Medical Center Manila - Medicine	Manila		Philippines
18	East Avenue Medical Center	Quezon City		Philippines
19	Lung Center of the Philippines - Medicine	Quezon		Philippines
20	Quirino Memorial Medical Center	Quezon		Philippines
21	Veterans Memorial Medical Center	Quezon		Philippines

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2021
• Statistical Analysis Plan - Apr 29, 2021

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT04448756
• Other Study ID Numbers: MS200569_0026; 2020-002248-22
• First Posted: Jun 26, 2020
• Last Update Posted: Jun 6, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMD Serono Research & Development Institute, Inc.: COVID-19; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
• Additional relevant MeSH terms: COVID-19; Pneumonia; Coronavirus Infections

Study Results

Participant Flow

Recruitment Details	Overall, 200 participants were screened for this study. Of which, 149 participants were randomized into the study.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Period Title: Overall Study
STARTED	49	54	46
COMPLETED	46	49	45
NOT COMPLETED	3	5	1

Baseline Characteristics

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg	Total
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.	Total of all reporting groups
Overall Participants	49	54	46	149
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.4 (14.09)	51.0 (12.25)	49.2 (12.35)	49.6 (12.87)
Sex: Female, Male (Count of Participants)
Female	18 36.7%	19 35.2%	14 30.4%	51 34.2%
Male	31 63.3%	35 64.8%	32 69.6%	98 65.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 59.2%	38 70.4%	29 63%	96 64.4%
Not Hispanic or Latino	20 40.8%	15 27.8%	15 32.6%	50 33.6%
Unknown or Not Reported	0 0%	1 1.9%	2 4.3%	3 2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	13 26.5%	16 29.6%	12 26.1%	41 27.5%
Native Hawaiian or Other Pacific Islander	1 2%	0 0%	0 0%	1 0.7%
Black or African American	3 6.1%	7 13%	4 8.7%	14 9.4%
White	22 44.9%	20 37%	25 54.3%	67 45%
More than one race	6 12.2%	7 13%	0 0%	13 8.7%
Unknown or Not Reported	4 8.2%	4 7.4%	5 10.9%	13 8.7%

Outcome Measures

1. Primary Outcome

Title	Time to Recovery
Description	Time to recovery was defined as the time from first dose (Day 1) to first occurrence of World Health Organization (WHO) 9-point ordinal scale 3 or less. The scoring is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or Extracorporeal membrane oxygenation (ECMO); 8. Death.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	3.4	3.7	3.9

2. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious TEAEs (SAEs) According to NCI-CTCAE Version 5.0
Description	Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Participants with any TEAE	28 57.1%	34 63%	26 56.5%
Participants with any AESIs	2 4.1%	2 3.7%	0 0%
Participants with TEAEs leading to discontinuation	4 8.2%	4 7.4%	1 2.2%
Participants with Serious TEAEs	9 18.4%	5 9.3%	1 2.2%

3. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Description	Laboratory investigation included hematology and biochemistry. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Count of Participants [Participants]	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements
Description	12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Count of Participants [Participants]	1 2%	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Alive and Not Requiring Supplemental Oxygenation
Description	The percentage of participants who were alive and did not require supplemental oxygenation or ventilatory support (including noninvasive or mechanical ventilation and Extra Corporeal Membrane Oxygenation [ECMO]) reported.
Time Frame	Day 3, Day 7, Day 14, Day 21 and Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	51	44
At Day 3	30.6 62.4%	27.5 50.9%	38.6 83.9%
At Day 7	76.6 156.3%	83.3 154.3%	83.3 181.1%
At Day 14	89.6 182.9%	89.8 166.3%	100.0 217.4%
At Day 21	93.0 189.8%	93.8 173.7%	100.0 217.4%
At Day 28	93.8 191.4%	98.0 181.5%	97.7 212.4%

6. Secondary Outcome

Title	Number of Participants in Each Clinical Status Category Based on 9-Point Ordinal Scale
Description	Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors or ECMO; 8. Death.
Time Frame	Baseline, Day 2, Day 3, Day 4, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 44, Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	53	46
Participants with Scale 0 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 1 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 2 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 3 at Baseline	1 2%	0 0%	0 0%
Participants with Scale 4 at Baseline	48 98%	52 96.3%	44 95.7%
Participants with Scale 5 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 6 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 7 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 8 at Baseline	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 2	0 0%	0 0%	0 0%
Participants with Scale 1 at Day 2	1 2%	0 0%	0 0%
Participants with Scale 2 at Day 2	0 0%	1 1.9%	2 4.3%
Participants with Scale 3 at Day 2	9 18.4%	12 22.2%	13 28.3%
Participants with Scale 4 at Day 2	35 71.4%	39 72.2%	30 65.2%
Participants with Scale 5 at Day 2	3 6.1%	0 0%	1 2.2%
Participants with Scale 6 at Day 2	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 2	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 2	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 3	0 0%	0 0%	0 0%
Participants with Scale 1 at Day 3	2 4.1%	2 3.7%	1 2.2%
Participants with Scale 2 at Day 3	1 2%	3 5.6%	2 4.3%
Participants with Scale 3 at Day 3	12 24.5%	9 16.7%	14 30.4%
Participants with Scale 4 at Day 3	29 59.2%	36 66.7%	26 56.5%
Participants with Scale 5 at Day 3	4 8.2%	0 0%	1 2.2%
Participants with Scale 6 at Day 3	1 2%	1 1.9%	0 0%
Participants with Scale 7 at Day 3	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 3	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 4	0 0%	0 0%	0 0%
Participants with Scale 1 at Day 4	0 0%	1 1.9%	0 0%
Participants with Scale 2 at Day 4	0 0%	1 1.9%	0 0%
Participants with Scale 3 at Day 4	14 28.6%	16 29.6%	11 23.9%
Participants with Scale 4 at Day 4	17 34.7%	22 40.7%	21 45.7%
Participants with Scale 5 at Day 4	5 10.2%	1 1.9%	0 0%
Participants with Scale 6 at Day 4	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 4	1 2%	0 0%	0 0%
Participants with Scale 8 at Day 4	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 5	0 0%	1 1.9%	0 0%
Participants with Scale 1 at Day 5	9 18.4%	6 11.1%	6 13%
Participants with Scale 2 at Day 5	4 8.2%	5 9.3%	4 8.7%
Participants with Scale 3 at Day 5	13 26.5%	18 33.3%	16 34.8%
Participants with Scale 4 at Day 5	11 22.4%	14 25.9%	14 30.4%
Participants with Scale 5 at Day 5	6 12.2%	3 5.6%	0 0%
Participants with Scale 6 at Day 5	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 5	2 4.1%	0 0%	0 0%
Participants with Scale 8 at Day 5	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 7	0 0%	1 1.9%	1 2.2%
Participants with Scale 1 at Day 7	15 30.6%	16 29.6%	15 32.6%
Participants with Scale 2 at Day 7	11 22.4%	9 16.7%	8 17.4%
Participants with Scale 3 at Day 7	10 20.4%	14 25.9%	11 23.9%
Participants with Scale 4 at Day 7	4 8.2%	5 9.3%	7 15.2%
Participants with Scale 5 at Day 7	5 10.2%	2 3.7%	0 0%
Participants with Scale 6 at Day 7	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 7	2 4.1%	0 0%	0 0%
Participants with Scale 8 at Day 7	0 0%	0 0%	0 0%
Participants with Scale 0 at Day 10	5 10.2%	2 3.7%	2 4.3%
Participants with Scale 1 at Day 10	16 32.7%	21 38.9%	18 39.1%
Participants with Scale 2 at Day 10	8 16.3%	4 7.4%	7 15.2%
Participants with Scale 3 at Day 10	5 10.2%	10 18.5%	7 15.2%
Participants with Scale 4 at Day 10	5 10.2%	2 3.7%	1 2.2%
Participants with Scale 5 at Day 10	2 4.1%	2 3.7%	0 0%
Participants with Scale 6 at Day 10	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 10	1 2%	0 0%	0 0%
Participants with Scale 8 at Day 10	1 2%	0 0%	0 0%
Participants with Scale 0 at Day 14	5 10.2%	5 9.3%	6 13%
Participants with Scale 1 at Day 14	26 53.1%	25 46.3%	23 50%
Participants with Scale 2 at Day 14	7 14.3%	8 14.8%	8 17.4%
Participants with Scale 3 at Day 14	5 10.2%	6 11.1%	7 15.2%
Participants with Scale 4 at Day 14	2 4.1%	3 5.6%	0 0%
Participants with Scale 5 at Day 14	0 0%	1 1.9%	0 0%
Participants with Scale 6 at Day 14	1 2%	1 1.9%	0 0%
Participants with Scale 7 at Day 14	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 14	2 4.1%	0 0%	0 0%
Participants with Scale 0 at Day 21	8 16.3%	8 14.8%	7 15.2%
Participants with Scale 1 at Day 21	22 44.9%	30 55.6%	35 76.1%
Participants with Scale 2 at Day 21	9 18.4%	7 13%	1 2.2%
Participants with Scale 3 at Day 21	1 2%	0 0%	0 0%
Participants with Scale 4 at Day 21	0 0%	2 3.7%	0 0%
Participants with Scale 5 at Day 21	0 0%	0 0%	0 0%
Participants with Scale 6 at Day 21	0 0%	1 1.9%	0 0%
Participants with Scale 7 at Day 21	1 2%	0 0%	0 0%
Participants with Scale 8 at Day 21	2 4.1%	0 0%	0 0%
Participants with Scale 0 at Day 28	14 28.6%	11 20.4%	15 32.6%
Participants with Scale 1 at Day 28	24 49%	35 64.8%	24 52.2%
Participants with Scale 2 at Day 28	5 10.2%	3 5.6%	4 8.7%
Participants with Scale 3 at Day 28	2 4.1%	1 1.9%	0 0%
Participants with Scale 4 at Day 28	1 2%	0 0%	1 2.2%
Participants with Scale 5 at Day 28	0 0%	0 0%	0 0%
Participants with Scale 6 at Day 28	0 0%	0 0%	0 0%
Participants with Scale 7 at Day 28	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 28	2 4.1%	1 1.9%	0 0%
Participants with Scale 0 at Day 44	17 34.7%	17 31.5%	22 47.8%
Participants with Scale 1 at Day 44	23 46.9%	30 55.6%	20 43.5%
Participants with Scale 2 at Day 44	4 8.2%	4 7.4%	1 2.2%
Participants with Scale 3 at Day 44	2 4.1%	0 0%	0 0%
Participants with Scale 4 at Day 44	0 0%	0 0%	0 0%
Participants with Scale 5 at Day 44	0 0%	0 0%	0 0%
Participants with Scale 6 at Day 44	0 0%	0 0%	0 0%
Participants with Scale 7 at Day 44	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 44	2 4.1%	1 1.9%	0 0%
Participants with Scale 0 at Day 60	18 36.7%	17 31.5%	22 47.8%
Participants with Scale 1 at Day 60	24 49%	31 57.4%	22 47.8%
Participants with Scale 2 at Day 60	3 6.1%	2 3.7%	1 2.2%
Participants with Scale 3 at Day 60	0 0%	0 0%	0 0%
Participants with Scale 4 at Day 60	0 0%	0 0%	0 0%
Participants with Scale 5 at Day 60	0 0%	0 0%	0 0%
Participants with Scale 6 at Day 60	0 0%	0 0%	0 0%
Participants with Scale 7 at Day 60	0 0%	0 0%	0 0%
Participants with Scale 8 at Day 60	2 4.1%	1 1.9%	0 0%

7. Secondary Outcome

Title	Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours in Room Air
Description	SpO2 is an estimate of the amount of oxygen in the blood. It is the percentage of hemoglobin containing oxygen compared to the total amount of hemoglobin in the blood (that is, oxygenated hemoglobin versus oxygenated and non-oxygenated hemoglobin). SpO2 measured by pulse oximetry. The time to SPO2 greater than or equal to (>=) 94 percent (%) sustained for at least 24 hours in room air is reported in days.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	4.7	4.8	5.0

8. Secondary Outcome

Title	Percentage of Participants With All-Cause Mortality
Description	Percentage of Participants who died for any reason reported.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Number (95% Confidence Interval) [Percentage of participants]	4.1 8.4%	1.9 3.5%	0.0 0%

9. Secondary Outcome

Title	Time to Intensive Care Unit (ICU) Admission
Description	Time to ICU admission was defined as the time from first dose (Day 1) to the date/time of ICU admission, or death, whichever occurs first, in days. Event-free survival function for time to event (ICU admission or death) estimated via Kaplan-Meier method.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	NA	NA	NA

10. Secondary Outcome

Title	Time to Non-Invasive Mechanical Ventilation
Description	Time to non-invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status >= 5, in days. Event-free survival function for time to event (Non-invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	NA	NA	NA

11. Secondary Outcome

Title	Time to Invasive Mechanical Ventilation
Description	Time to invasive mechanical ventilation was defined as the time from first dose (Day 1) to the date/time of clinical status >= 6, in days. Event-free survival function for time to event (invasive mechanical ventilation or death) estimated via Kaplan-Meier method. Clinical status was based on data collected on the 'Ordinal Scale for Clinical Status and is assessed with the following ordinal scale: 0. Uninfected: no clinical or virological evidence of infection; 1. Ambulatory: no limitation of activities; 2. Ambulatory: limitation of activities; 3. Hospitalized, mild disease: hospitalized, no oxygen therapy; 4. Hospitalized, mild disease: oxygen by mask or nasal prongs; 5. Hospitalized, severe disease: noninvasive ventilation or high-flow oxygen; 6. Hospitalized, severe disease: intubation and mechanical ventilation; 7. Hospitalized, severe disease: ventilation plus additional organ support for example: vasopressors, and ECMO; 8. Death.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	NA	NA	NA

12. Secondary Outcome

Title	Total Length of Stay in Intensive Care Unit (ICU)
Description	Total days in the ICU was defined as the sum, for all ICU admissions, of the time from ICU admission to the date of ICU discharge, in days.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (Full Range) [Days]	7.1	10.2	3.7

13. Secondary Outcome

Title	Total Length of Hospitalization Stay
Description	Total days in the hospital was defined as the sum, for all hospitalization events, of the time from first dose to the date of hospital discharge in days.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (Full Range) [Days]	7.0	6.0	6.0

14. Secondary Outcome

Title	Time to Hospital Discharge
Description	The time to hospital discharge, defined as the time from first dose (Day 1) to the date of first hospitalization discharge, in days.
Time Frame	Day 1 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Median (95% Confidence Interval) [Days]	5.1	5.1	4.7

15. Secondary Outcome

Title	Percent Change From Baseline in Inflammatory Biomarkers Over Time
Description	C-Reactive Protein, D-Dimer and Ferritin inflammatory biomarkers were analyzed for this study. Percent Change From Baseline in Inflammatory Biomarkers Over Time were reported here.
Time Frame	Baseline, Day 3, Day7, Day 10, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description

Pharmacodynamics (PD) analysis set included all participants who received atleast 1 dose of study intervention, for whom atleast 1 postbaseline serum biomarker was obtained without any relevant protocol deviations or events that may have an influence on PD. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	41	39	35
Percent change at Day 3 in C-Reactive Protein	-0.8 (113.57)	48.2 (399.18)	-45.1 (59.64)
Percent change at Day 7 in C-Reactive Protein	-48.1 (69.03)	-50.4 (133.43)	-74.3 (32.19)
Percent change at Day 10 in C-Reactive Protein	10.5 (182.35)	-58.2 (43.93)	-68.3 (81.09)
Percent change at Day 14 in C-Reactive Protein	-62.1 (39.95)	24.6 (543.06)	-51.2 (159.45)
Percent change at Day 28 in C-Reactive Protein	-62.0 (91.47)	-27.0 (253.69)	-72.4 (45.01)
Percent change at Day 3 in D-Dimer	62.5 (150.19)	2008.7 (11813.54)	2093.9 (11278.04)
Percent change at Day 7 in D-Dimer	184.5 (517.94)	35.4 (197.99)	1922.7 (9449.18)
Percent change at Day 10 in D-Dimer	2004.2 (5139.01)	62.6 (202.41)	171.3 (501.83)
Percent change at Day 14 in D-Dimer	1136.7 (6760.10)	0.7 (86.62)	15.1 (100.97)
Percent change at Day 28 in D-Dimer	893.4 (4731.82)	-5.9 (61.09)	1371.6 (6985.20)
Percent change at Day 3 in Ferritin	17.8 (83.23)	3.4 (43.05)	-7.2 (20.63)
Percent change at Day 7 in Ferritin	11.1 (151.34)	-22.7 (40.53)	-19.8 (27.64)
Percent change at Day 10 in Ferritin	21.4 (167.00)	-25.4 (31.52)	-39.7 (25.13)
Percent change at Day 14 in Ferritin	-29.4 (117.71)	-47.8 (31.56)	-49.9 (18.54)
Percent change at Day 28 in Ferritin	-61.3 (35.83)	-62.3 (25.83)	-63.2 (15.71)

16. Secondary Outcome

Title	Percent Change From Baseline in Serum Cytokine Biomarkers
Description	Interleukin 6 and Interleukin 8 serum cytokine biomarkers were analyzed. Percent Change From Baseline in Serum Cytokine Biomarkers were reported.
Time Frame	Baseline, Day 3, Day7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description

PD analysis set included all participants who received at least 1 dose of study intervention, for whom at least 1 postbaseline serum biomarker was obtained without any relevant protocol deviations or events that may have an influence on PD. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	38	38	35
Percent change at Day 3 in Interleukin 6	51.2 (257.64)	-17.8 (38.95)	1722.3 (10240.47)
Percent change at Day 7 in Interleukin 6	35.2 (167.99)	1.1 (159.45)	-25.5 (42.41)
Percent change at Day 14 in Interleukin 6	20.2 (164.19)	55.2 (476.42)	275.1 (1745.50)
Percent change at Day 28 in Interleukin 6	-21.0 (41.33)	-27.3 (37.78)	-30.1 (36.93)
Percent change at Day 3 in Interleukin 8	42.5 (165.56)	2.0 (77.66)	126.6 (574.74)
Percent change at Day 7 in Interleukin 8	923.4 (4432.63)	60.2 (253.12)	28.5 (113.48)
Percent change at Day 14 in Interleukin 8	408.9 (1776.87)	35.4 (147.85)	283.5 (1616.08)
Percent change at Day 28 in Interleukin 8	-4.3 (90.29)	-13.0 (59.00)	-1.8 (123.62)

17. Secondary Outcome

Title	Percentage of Participants With Relapse
Description	Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.
Time Frame	Day 5 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Number (95% Confidence Interval) [Percentage of participants]	0.0 0%	0.0 0%	0.0 0%

18. Secondary Outcome

Title	Percentage of Participants Who Are Re-Hospitalized
Description	Percentage or participants who are re-hospitalized due to coronavirus disease 2019 (Covid-19) complications were reported.
Time Frame	Day 5 through Day 60

Outcome Measure Data

Analysis Population Description

Intent-to-Treat analysis set included all participants who had received at least one dose of study intervention.

Arm/Group Title	Placebo	M5049 50 Milligram (mg)	M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.	Participants received M5049 50 milligram (mg) orally twice daily for 14 days.	Participants received M5049 100 mg orally twice daily for 14 days.
Measure Participants	49	54	46
Number (95% Confidence Interval) [Percentage of participants]	0.0 0%	0.0 0%	2.2 4.8%

Adverse Events

Time Frame	Baseline up to Day 60
Arm/Group Title	Placebo		M5049 50 Milligram (mg)		M5049 100 mg
Arm/Group Description	Participants received matched placebo tablets to M5049 daily for 14 days.		Participants received M5049 50 milligram (mg) orally twice daily for 14 days.		Participants received M5049 100 mg orally twice daily for 14 days.
All Cause Mortality
	Placebo		M5049 50 Milligram (mg)		M5049 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/49 (4.1%)		1/54 (1.9%)		0/46 (0%)
Serious Adverse Events
	Placebo		M5049 50 Milligram (mg)		M5049 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/49 (18.4%)		5/54 (9.3%)		1/46 (2.2%)
Blood and lymphatic system disorders
Anaemia	1/49 (2%)		0/54 (0%)		0/46 (0%)
Gastrointestinal disorders
Gastric ulcer	1/49 (2%)		0/54 (0%)		0/46 (0%)
Upper gastrointestinal haemorrhage	1/49 (2%)		0/54 (0%)		0/46 (0%)
Infections and infestations
Clostridium difficile infection	1/49 (2%)		0/54 (0%)		0/46 (0%)
COVID-19	3/49 (6.1%)		4/54 (7.4%)		0/46 (0%)
Sepsis	2/49 (4.1%)		0/54 (0%)		0/46 (0%)
Investigations
Oxygen saturation decreased	2/49 (4.1%)		0/54 (0%)		0/46 (0%)
Metabolism and nutrition disorders
Diabetic metabolic decompensation	0/49 (0%)		1/54 (1.9%)		0/46 (0%)
Nervous system disorders
Carpal tunnel syndrome	1/49 (2%)		0/54 (0%)		0/46 (0%)
Renal and urinary disorders
Acute kidney injury	1/49 (2%)		0/54 (0%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/49 (0%)		0/54 (0%)		1/46 (2.2%)
Respiratory failure	1/49 (2%)		0/54 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		M5049 50 Milligram (mg)		M5049 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/49 (24.5%)		15/54 (27.8%)		10/46 (21.7%)
Cardiac disorders
Sinus bradycardia	0/49 (0%)		1/54 (1.9%)		3/46 (6.5%)
Gastrointestinal disorders
Constipation	2/49 (4.1%)		6/54 (11.1%)		0/46 (0%)
Diarrhoea	0/49 (0%)		4/54 (7.4%)		0/46 (0%)
Investigations
Alanine aminotransferase increased	6/49 (12.2%)		1/54 (1.9%)		1/46 (2.2%)
Transaminases increased	1/49 (2%)		3/54 (5.6%)		1/46 (2.2%)
Metabolism and nutrition disorders
Hypokalaemia	1/49 (2%)		3/54 (5.6%)		4/46 (8.7%)
Psychiatric disorders
Insomnia	4/49 (8.2%)		1/54 (1.9%)		1/46 (2.2%)
Skin and subcutaneous tissue disorders
Rash	1/49 (2%)		0/54 (0%)		3/46 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.