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Clinical Trial Results:
A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19

Summary
EudraCT number	2020-003690-21
Trial protocol	RO
Global end of trial date	09 Jun 2022

Results information
Results version number	v1(current)
This version publication date	24 Dec 2022
First version publication date	24 Dec 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

R10933-10987-COV-2067

ISRCTN number

US NCT number

NCT04425629

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron

Sponsor organisation address

777 Old Saw Mill River Road, Tarrytown, United States, 10591

Public contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643,

Scientific contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002964-PIP01-21 EMEA-002965-PIP01-21

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

09 Jun 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Jun 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

This study is an adaptive phase 1/2/3, randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) in outpatient (ie, ambulatory) adults with COVID-19

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Council for Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Jun 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 9359

Country: Number of subjects enrolled

Romania: 103

Country: Number of subjects enrolled

Mexico: 603

Worldwide total number of subjects

10065

EEA total number of subjects

103

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

102

Adolescents (12-17 years)

103

Adults (18-64 years)

8874

From 65 to 84 years

940

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

10065 were randomized, 135 randomized but not treated

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Phase 1 Symptomatic: Placebo

Arm description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 1 Symptomatic: 2.4 IV

Arm description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg total (1200 mg of each mAb)

Phase 1 Symptomatic: 8.0 IV

Arm description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

8000 mg total (4000 mg of each mAb)

Phase 2 Symptomatic: Placebo

Arm description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 2 Symptomatic: 2.4 IV

Arm description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg total (1200 mg of each mAb)

Phase 2 Symptomatic: 8.0 IV

Arm description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

8000 mg total (4000 mg of each mAb)

Phase 2 Asymptomatic: Placebo

Arm description

Placebo of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 2 Asymptomatic: 2.4 IV

Arm description

2.4g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg total (1200 mg of each mAb)

Phase 2 Asymptomatic: 8.0 IV

Arm description

8.0g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

8000 mg total (4000 mg of each mAb)

Phase 3 Age>=18: Placebo

Arm description

Placebo of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 3 Age>=18: 1.2 IV

Arm description

1.2g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg total (600 mg of each mAb)

Phase 3 Age>=18: 2.4 IV

Arm description

2.4g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg total (1200 mg of each mAb)

Phase 3 Age>=18: 8.0 IV

Arm description

8.0g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

8000 mg total (4000 mg of each mAb)

Phase 3 Age <18: Placebo

Arm description

Placebo of R10933 + R10987 Participants <18 with COVID-19, not pregnant at randomization

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 3 Age <18: 1.2 IV

Arm description

1.2g of R10933 + R10987 Participants <18 with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

For patients <18 years, weight-tiered dosing was employed: 1200 mg IV treatment group ≥40 kg: 1200 mg total ≥20 kg to <40 kg: 450 mg total ≥10 kg to <20 kg: 224 mg total ≥5 kg to <10 kg: 120 mg total ≥2.5 kg to <5 kg: 60 mg total <2.5 kg: 30 mg total

Phase 3 Age <18: 2.4 IV

Arm description

2.4g of R10933 + R10987 Participants <18 with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

For patients <18 years, weight-tiered dosing was employed: 2400 mg IV treatment group ≥40 kg: 2400 mg total ≥20 kg to <40 kg: 900 mg total ≥10 kg to <20 kg: 450 mg total ≥5 kg to <10 kg: 240 mg total ≥2.5 kg to <5 kg: 120 mg total <2.5 kg: 60 mg total

Phase 3 Pregnant Placebo

Arm description

Placebo of R10933 + R10987 Participants who are pregnant with COVID-19

Arm type

Placebo

Investigational medicinal product name

Placebo for Casirivimab and Placebo for Imdevimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Single IV dose of placebo

Phase 3 Pregnant 1.2 IV

Arm description

1.2g of R10933 + R10987 Participants who are pregnant with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg total (600 mg of each mAb)

Phase 3 Pregnant: 2.4 IV

Arm description

2.4g of R10933 + R10987 Participants who are pregnant with COVID-19

Arm type

Experimental

Investigational medicinal product name

Casirivimab (R10933) + Imdevimab (R10987)

Investigational medicinal product code

R10933 + R10987

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg total (1200 mg of each mAb)

Number of subjects in period 1	Phase 1 Symptomatic: Placebo	Phase 1 Symptomatic: 2.4 IV	Phase 1 Symptomatic: 8.0 IV	Phase 2 Symptomatic: Placebo	Phase 2 Symptomatic: 2.4 IV	Phase 2 Symptomatic: 8.0 IV	Phase 2 Asymptomatic: Placebo	Phase 2 Asymptomatic: 2.4 IV	Phase 2 Asymptomatic: 8.0 IV	Phase 3 Age>=18: Placebo	Phase 3 Age>=18: 1.2 IV	Phase 3 Age>=18: 2.4 IV	Phase 3 Age>=18: 8.0 IV	Phase 3 Age <18: Placebo	Phase 3 Age <18: 1.2 IV	Phase 3 Age <18: 2.4 IV	Phase 3 Pregnant Placebo	Phase 3 Pregnant 1.2 IV	Phase 3 Pregnant: 2.4 IV
Started	24	24	24	242	242	243	76	76	76	2378	2156	3189	1027	2	129	75	3	43	36
Completed	23	19	22	230	232	233	71	73	74	2217	1974	2947	962	2	123	65	2	40	33
Not completed	1	5	2	12	10	10	5	3	2	161	182	242	65	0	6	10	1	3	3
Physician decision	-	-	-	-	-	-	-	-	-	4	3	5	1	-	-	1	-	-	-
Subject Decision	-	2	1	3	6	6	3	3	1	70	95	124	25	-	1	4	1	-	2
Adverse event, non-fatal	-	-	-	-	1	-	-	-	-	3	2	1	1	-	-	-	-	-	-
Death	-	-	-	-	-	-	-	-	-	11	2	4	-	-	-	-	-	-	-
Lost to follow-up	1	3	1	7	1	2	1	-	1	64	70	98	30	-	5	4	-	3	1
Sponsor Request	-	-	-	2	2	2	1	-	-	9	9	10	8	-	-	1	-	-	-
Lack of efficacy	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

Phase 1 Symptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Asymptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 3 Age>=18: Placebo

Reporting group description

Placebo of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age <18: Placebo

Reporting group description

Placebo of R10933 + R10987 Participants <18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age <18: 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Age <18: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Pregnant Placebo

Reporting group description

Placebo of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group values	Phase 1 Symptomatic: Placebo	Phase 1 Symptomatic: 2.4 IV	Phase 1 Symptomatic: 8.0 IV	Phase 2 Symptomatic: Placebo	Phase 2 Symptomatic: 2.4 IV	Phase 2 Symptomatic: 8.0 IV	Phase 2 Asymptomatic: Placebo	Phase 2 Asymptomatic: 2.4 IV	Phase 2 Asymptomatic: 8.0 IV	Phase 3 Age>=18: Placebo	Phase 3 Age>=18: 1.2 IV	Phase 3 Age>=18: 2.4 IV	Phase 3 Age>=18: 8.0 IV	Phase 3 Age <18: Placebo	Phase 3 Age <18: 1.2 IV	Phase 3 Age <18: 2.4 IV	Phase 3 Pregnant Placebo	Phase 3 Pregnant 1.2 IV	Phase 3 Pregnant: 2.4 IV	Total
Number of subjects	24	24	24	242	242	243	76	76	76	2378	2156	3189	1027	2	129	75	3	43	36	10065
Age Categorical
Units: Participants
<18	0	0	0	0	0	0	0	0	0	0	0	0	0	2	129	75	0	0	1	207
>=18, <65	22	23	23	226	223	228	71	62	65	2159	1937	2843	911	0	0	0	3	43	35	8874
>=65	2	1	1	16	19	15	5	14	11	219	219	346	116	0	0	0	0	0	0	984
Age Continuous
Units: years
median (full range (min-max))	40.5 (18 to 72)	39.5 (18 to 65)	39.0 (20 to 72)	42.0 (18 to 89)	43.0 (18 to 85)	42.0 (19 to 80)	43.5 (18 to 80)	44.5 (18 to 75)	44.5 (18 to 84)	46.0 (18 to 92)	48.0 (18 to 93)	46.0 (18 to 96)	44.0 (18 to 90)	14.0 (12 to 16)	11.0 (0 to 17)	12.0 (3 to 17)	33.0 (27 to 33)	30.0 (19 to 41)	28.0 (17 to 41)	-
Gender Categorical
Units: Subjects
Female	10	14	10	122	130	136	40	37	32	1227	1117	1635	518	2	69	22	3	43	36	5203
Male	14	10	14	120	112	107	36	39	44	1151	1039	1554	509	0	60	53	0	0	0	4862
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	8	11	17	129	121	117	34	43	35	1002	1140	1413	316	0	87	40	0	6	8	4527
Not Hispanic or Latino	16	12	6	112	121	126	40	33	39	1357	992	1740	701	2	42	33	2	37	28	5439
Not Reported	0	1	1	1	0	0	2	0	2	19	24	36	10	0	0	2	1	0	0	99
Race
Units: Subjects
White	20	16	23	207	208	207	65	69	65	2010	1704	2612	889	1	115	63	2	35	33	8344
Black or African American	3	7	0	21	20	23	6	3	5	110	112	172	46	1	8	7	1	4	2	551
Asian	0	0	0	4	6	4	1	4	3	89	71	96	45	0	1	1	0	0	0	325
American Indian or Alaska Native	1	0	0	2	1	1	0	0	0	30	72	84	5	0	0	0	0	1	0	197
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	3	7	6	0	0	0	0	0	1	0	17
Unknown	0	0	0	3	1	3	2	0	3	82	138	143	21	0	3	2	0	1	0	402
Not Reported	0	1	1	5	6	5	2	0	0	54	52	76	21	0	2	2	0	1	1	229
Age Continous
Units: years
arithmetic mean (standard deviation)	43.8 ± 14.42	38.9 ± 11.11	40.4 ± 11.83	42.5 ± 15.21	42.7 ± 15.59	41.7 ± 14.38	43.5 ± 15.51	44.8 ± 16.70	44.0 ± 17.43	45.4 ± 14.61	46.7 ± 14.59	46.1 ± 14.89	44.8 ± 15.09	14.0 ± 2.83	10.9 ± 4.14	12.2 ± 3.36	31.0 ± 3.46	28.9 ± 5.87	28.3 ± 6.02	-

End points

Top of page

Reporting group title

Phase 1 Symptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Asymptomatic: Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 3 Age>=18: Placebo

Reporting group description

Placebo of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18: 8.0 IV

Reporting group description

8.0g of R10933 + R10987 Participants >= 18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age <18: Placebo

Reporting group description

Placebo of R10933 + R10987 Participants <18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age <18: 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Age <18: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Pregnant Placebo

Reporting group description

Placebo of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant 1.2 IV

Reporting group description

1.2g of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant: 2.4 IV

Reporting group description

2.4g of R10933 + R10987 Participants who are pregnant with COVID-19

Subject analysis set title

Phase 1 + Phase 2 Symptomatic (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Combined Phase 1 + Phase 2 Symptomatic Placebo Participants

Subject analysis set title

Phase 1 + Phase 2 Symptomatic (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Combined Phase 1 + Phase 2 Symptomatic 2.4g IV Participants

Subject analysis set title

Phase 1 + Phase 2 Symptomatic (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Combined Phase 1 + Phase 2 Symptomatic 8.0g IV Participants

Subject analysis set title

Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pooled analysis of Phases 1, 2, & 3 Cohort 1 Symptomatic Participants for Placebo

Subject analysis set title

Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pooled analysis of Phases 1, 2, & 3 Cohort 1 Symptomatic Participants for dosage of 1.2g IV

Subject analysis set title

Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pooled analysis of Phases 1, 2, & 3 Cohort 1 Symptomatic Participants for dosage of 2.4g IV

Subject analysis set title

Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pooled analysis of Phases 1, 2, & 3 Cohort 1 Symptomatic Participants for dosage of 8.0g IV

Subject analysis set title

Phase 3 Cohort 2 Pediatric (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 Pediatric (Placebo)

Subject analysis set title

Phase 3 Cohort 2 Pediatric (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 Pediatric (1.2g IV)

Subject analysis set title

Phase 3 Cohort 2 Pediatric (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 Pediatric (2.4g IV)

Subject analysis set title

Phase 3 Cohort 3 Pregnant (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 Pregnant (Placebo)

Subject analysis set title

Phase 3 Cohort 3 Pregnant (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 Pregnant (1.2g IV)

Subject analysis set title

Phase 3 Cohort 3 Pregnant (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 Pregnant (2.4g IV)

Subject analysis set title

Phase 3 Cohort 1 (Placebo) >=18

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (Placebo)

Subject analysis set title

Phase 3 Cohort 1 (1.2g IV) >= 18

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (1.2g IV)

Subject analysis set title

Phase 3 Cohort 1 (2.4g IV) >= 18

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (2.4g IV)

Subject analysis set title

Phase 3 Cohort 1 (8.0g IV) >= 18

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (8.0g IV)

Subject analysis set title

Phase 3 Cohort 1 (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (Placebo) - Post PA6 mFAS

Subject analysis set title

Phase 3 Cohort 1 (1.2 g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (1.2 g IV) - Post PA6 mFAS

Subject analysis set title

Phase 1 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 1 (2.4g IV) - PK Analysis Set

Subject analysis set title

Phase 1 (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 1 (8.0g IV) - PK Analysis Set

Subject analysis set title

Phase 2 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 2 (2.4g IV) - PK Analysis Set

Subject analysis set title

Phase 2 (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 2 (8.0g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 1 (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (1.2g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 1 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (2.4g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 1 (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 1 (8.0g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 3 (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 (1.2g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 3 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 (2.4g IV) - PK Analysis Set

Subject analysis set title

Phase 3 Cohort 2 (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 (Placebo) - ADA Analysis Set

Subject analysis set title

Phase 3 Cohort 2 (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 (1.2g IV) - ADA Analysis Set

Subject analysis set title

Phase 3 Cohort 2 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 2 (2.4g IV) - ADA Analysis Set

Subject analysis set title

Phase 3 Cohort 3 (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 (Placebo) - ADA Analysis Set

Subject analysis set title

Phase 3 Cohort 3 (1.2g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 (1.2g IV) - ADA Analysis Set

Subject analysis set title

Phase 3 Cohort 3 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 3 Cohort 3 (2.4g IV) - ADA Analysis Set

Subject analysis set title

Next Phase 2 (Placebo)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Next Phase 2 Placebo Participants

Subject analysis set title

Next Phase 2 (2.4g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Next Phase 2 Participants 2.4g IV

Subject analysis set title

Next Phase 2 (8.0g IV)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Next Phase 2 Participants 8.0g IV

Subject analysis set title

Phase 1 PK-AS

Subject analysis set type

Sub-group analysis

Subject analysis set description

Phase 1 PK-AS (Pharmacokinetic Analysis Set)

Primary: Number of Participants with treatment-emergent serious adverse events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]

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End point title

Number of Participants with treatment-emergent serious adverse events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] ^[1]

End point description

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1) Pooled analysis of the symptomatic patients only, randomized up to 24-Feb with >= 1 risk factor

End point type

Primary

End point timeframe

Through Day 29

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point

End point values	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)	Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)	Phase 3 Cohort 2 Pediatric (Placebo)	Phase 3 Cohort 2 Pediatric (1.2g IV)	Phase 3 Cohort 2 Pediatric (2.4g IV)	Phase 3 Cohort 3 Pregnant (Placebo)	Phase 3 Cohort 3 Pregnant (1.2g IV)	Phase 3 Cohort 3 Pregnant (2.4g IV)
Number of subjects analysed	2609	1329	2614	1272	2	129	71	2	43	35
Units: Participant	97	14	31	19	0	2	0	0	2	2

No statistical analyses for this end point

Primary: Number of Participants with infusion-related reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

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End point title

Number of Participants with infusion-related reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) ^[2]

End point description

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

End point type

Primary

End point timeframe

Through Day 4

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point

End point values	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)	Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)	Phase 3 Cohort 2 Pediatric (Placebo)	Phase 3 Cohort 2 Pediatric (1.2g IV)	Phase 3 Cohort 2 Pediatric (2.4g IV)	Phase 3 Cohort 3 Pregnant (Placebo)	Phase 3 Cohort 3 Pregnant (1.2g IV)	Phase 3 Cohort 3 Pregnant (2.4g IV)
Number of subjects analysed	2609	1329	2614	1272	2	129	71	2	43	35
Units: Participants	2	1	4	7	0	0	1	0	0	0

No statistical analyses for this end point

Primary: Number of participants with hypersensitivity reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

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End point title

Number of participants with hypersensitivity reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) ^[3]

End point description

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

End point type

Primary

End point timeframe

Through Day 29

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point

End point values	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)	Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)	Phase 3 Cohort 2 Pediatric (Placebo)	Phase 3 Cohort 2 Pediatric (1.2g IV)	Phase 3 Cohort 2 Pediatric (2.4g IV)	Phase 3 Cohort 3 Pregnant (Placebo)	Phase 3 Cohort 3 Pregnant (1.2g IV)	Phase 3 Cohort 3 Pregnant (2.4g IV)
Number of subjects analysed	2609	1329	2614	1272	2	129	71	2	43	35
Units: Participants	3	1	1	0	0	1	0	0	0	0

No statistical analyses for this end point

Primary: Time-weighted average change from baseline in viral load (log10 copies/mL) from Day 1 to Day 7, as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples (Ph1, Ph2)

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End point title

Time-weighted average change from baseline in viral load (log10 copies/mL) from Day 1 to Day 7, as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples (Ph1, Ph2)

End point description

Primary: Phase 1, Phase 2 All randomized patients with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated;

End point type

Primary

End point timeframe

Baseline up to Day 7

End point values	Phase 1 + Phase 2 Symptomatic (Placebo)	Phase 1 + Phase 2 Symptomatic (2.4g IV)	Phase 1 + Phase 2 Symptomatic (8.0g IV)
Number of subjects analysed	224	211	214
Units: log10 copies/mL
arithmetic mean (standard deviation)	-1.32 ± 1.047	-1.65 ± 0.977	-1.67 ± 1.157

Difference vs. Placebo by Day 7

Comparison groups

Phase 1 + Phase 2 Symptomatic (Placebo) v Phase 1 + Phase 2 Symptomatic (2.4g IV)

Number of subjects included in analysis

435

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

ANCOVA

Parameter type

LS Mean

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.1

Difference vs. Placebo by Day 7

Comparison groups

Phase 1 + Phase 2 Symptomatic (Placebo) v Phase 1 + Phase 2 Symptomatic (8.0g IV)

Number of subjects included in analysis

438

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

0.1

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1- 1.2g vs Placebo)

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End point title

Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1- 1.2g vs Placebo)

End point description

Phase 3 Cohort 1

End point type

Primary

End point timeframe

Through Day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (1.2g IV) >= 18
Number of subjects analysed	748	736
Units: Percentage of Participants
number (confidence interval 95%)	3.2 (2.1 to 4.7)	1.0 (0.4 to 1.9)

1.2g IV vs. Placebo

Comparison groups

Phase 3 Cohort 1 (Placebo) >=18 v Phase 3 Cohort 1 (1.2g IV) >= 18

Number of subjects included in analysis

1484

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0024

Method

Cochran-Mantel-Haenszel

Confidence interval

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1 - 2.4g vs Placebo)

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End point title

Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1 - 2.4g vs Placebo)

End point description

Primary: Phase 3 (Cohort 1)

End point type

Primary

End point timeframe

Through Day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (2.4g IV) >= 18
Number of subjects analysed	1341	1355
Units: Percentage of Participants
number (confidence interval 95%)	4.6 (3.6 to 5.9)	1.3 (0.8 to 2.1)

2.4g IV vs. Placebo

Comparison groups

Phase 3 Cohort 1 (2.4g IV) >= 18 v Phase 3 Cohort 1 (Placebo) >=18

Number of subjects included in analysis

2696

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Confidence interval

Primary: Concentration of REGN10983 + REGN10987 in Serum over time (Ph3 Cohort 2)

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End point title

Concentration of REGN10983 + REGN10987 in Serum over time (Ph3 Cohort 2) ^[4]

End point description

Phase 3 Cohort 2 [Nominal Sampling Time] = [Clinical Study Time (Visit Day – 1)]

End point type

Primary

End point timeframe

Up to Nominal Sampling Day 28

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point

End point values	Phase 3 Cohort 2 Pediatric (1.2g IV)	Phase 3 Cohort 2 Pediatric (2.4g IV)
Number of subjects analysed	123	64
Units: mg/L
arithmetic mean (standard deviation)
Day 0: End of Infusion (n=107, 51)	402 ± 196	710 ± 275
Nominal Sampling Day 28 (n= 94, 48)	108 ± 60.1	198 ± 78.7

No statistical analyses for this end point

Secondary: Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

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End point title

Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

End point description

Phase 3 Cohort 1

End point type

Secondary

End point timeframe

Up to Day 29

End point values	Phase 3 Cohort 1 (Placebo)	Phase 3 Cohort 1 (1.2 g IV)
Number of subjects analysed	680	673
Units: Days
median (confidence interval 95%)	14.0 (13.0 to 16.0)	10.0 (9.0 to 12.0)

No statistical analyses for this end point

Secondary: Time to COVID-19 symptoms resolution (Ph3 Cohort 1 - 2.4g vs Placebo)

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End point title

Time to COVID-19 symptoms resolution (Ph3 Cohort 1 - 2.4g vs Placebo) ^[5]

End point description

Phase 3 (Cohort 1)

End point type

Secondary

End point timeframe

Through Day 29

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for the baseline portion for these arms

End point values	Phase 3 Age>=18: Placebo	Phase 3 Age>=18: 2.4 IV
Number of subjects analysed	1197	1214
Units: Days
median (confidence interval 95%)	14.0 (13.0 to 15.0)	10.0 (10.0 to 11.0)

No statistical analyses for this end point

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

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End point title

Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

End point description

Phase 3 (Cohort 1)

End point type

Secondary

End point timeframe

Day 4 thru Day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (1.2g IV) >= 18
Number of subjects analysed	735	748
Units: Number of Participants	5	18

No statistical analyses for this end point

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

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End point title

Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

End point description

Phase 3 (Cohort 1)

End point type

Secondary

End point timeframe

From Day 4 Through Day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (2.4g IV) >= 18
Number of subjects analysed	1340	1351
Units: Number of Participants	46	5

No statistical analyses for this end point

Secondary: Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs (Next Phase 2 Cohort)

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End point title

Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs (Next Phase 2 Cohort)

End point description

Next Phase 2 Symptomatic

End point type

Secondary

End point timeframe

Day 5, Day 7, Day 15, Day 29

End point values	Next Phase 2 (Placebo)	Next Phase 2 (2.4g IV)	Next Phase 2 (8.0g IV)
Number of subjects analysed	151	145	146
Units: log10 copies/mL
least squares mean (standard error)
Day 5 (n=141, 139, 137, 54, 45, 47)	-1.79 ± 0.14	-2.33 ± 0.14	-2.28 ± 0.14
Day 7 (n=141, 139, 134, 55, 48, 48)	-2.54 ± 0.13	-2.79 ± 0.13	-3.08 ± 0.13
Day 15 (n=138, 140, 134, 56, 47, 50)	-4.56 ± 0.14	-4.67 ± 0.14	-4.58 ± 0.14
Day 29 (n=139, 136, 140, 54, 46, 46)	-5.42 ± 0.10	-5.60 ± 0.10	-5.45 ± 0.10

Difference vs. Placebo at Day 29

Comparison groups

Next Phase 2 (Placebo) v Next Phase 2 (2.4g IV)

Number of subjects included in analysis

296

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1903

Method

Mixed models analysis

Confidence interval

Difference vs. Placebo at Day 29

Comparison groups

Next Phase 2 (Placebo) v Next Phase 2 (8.0g IV)

Number of subjects included in analysis

297

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8431

Method

Mixed models analysis

Confidence interval

Secondary: Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days (Ph1, Ph2)

Top of page

End point title

Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days (Ph1, Ph2)

End point description

Phase 1, Phase 2

End point type

Secondary

End point timeframe

Day 1 to Day 29

End point values	Phase 1 + Phase 2 Symptomatic (Placebo)	Phase 1 + Phase 2 Symptomatic (2.4g IV)	Phase 1 + Phase 2 Symptomatic (8.0g IV)
Number of subjects analysed	151	145	146
Units: log10 copies/mL
least squares mean (standard error)
TWA Change from BL: Day 1 to Day 5	-0.91 ± 0.09	-1.25 ± 0.09	-1.19 ± 0.09
TWA Change from BL: Day 1 to Day 7	-1.34 ± 0.09	-1.71 ± 0.09	-1.68 ± 0.09
TWA Change from BL: Day 1 to Day 15	-2.58 ± 0.09	-2.96 ± 0.09	-2.99 ± 0.09
TWA Change from BL: Day 1 to Day 29	-3.76 ± 0.08	-4.05 ± 0.08	-4.08 ± 0.08

No statistical analyses for this end point

Secondary: Proportion of participants with ≥1 COVID-19-related medically-attended visit through Day 29 (Ph1, Ph2)

Top of page

End point title

Proportion of participants with ≥1 COVID-19-related medically-attended visit through Day 29 (Ph1, Ph2)

End point description

Phase 1, Phase 2

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 1 + Phase 2 Symptomatic (Placebo)	Phase 1 + Phase 2 Symptomatic (2.4g IV)	Phase 1 + Phase 2 Symptomatic (8.0g IV)
Number of subjects analysed	232	219	220
Units: Number of Visits
number (confidence interval 95%)	7.8 (4.7 to 12.0)	3.2 (1.3 to 6.5)	2.7 (1.0 to 5.8)

No statistical analyses for this end point

Secondary: Proportion of Participants with ≥1 COVID-19 related Hospitalization, Emergency Room, or Urgent Care visit through Day 29 (Ph1, Ph2)

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End point title

Proportion of Participants with ≥1 COVID-19 related Hospitalization, Emergency Room, or Urgent Care visit through Day 29 (Ph1, Ph2)

End point description

Phase 1, Phase 2

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 1 + Phase 2 Symptomatic (Placebo)	Phase 1 + Phase 2 Symptomatic (2.4g IV)	Phase 1 + Phase 2 Symptomatic (8.0g IV)
Number of subjects analysed	232	219	220
Units: Percentage of Visits
number (confidence interval 95%)	4.7 (2.4 to 8.3)	2.7 (1.0 to 5.9)	2.3 (0.7 to 5.2)

No statistical analyses for this end point

Secondary: Time to first onset of symptoms consistent with COVID-19 (Phase 2 asymptomatic cohort only)

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End point title

Time to first onset of symptoms consistent with COVID-19 (Phase 2 asymptomatic cohort only) ^[6]

End point description

Phase 2 Only

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for the baseline portion for these arms

End point values	Phase 2 Asymptomatic: 2.4 IV	Phase 2 Asymptomatic: 8.0 IV
Number of subjects analysed	40	42
Units: Time to Onset
arithmetic mean (confidence interval 95%)	0.76 (0.41 to 1.41)	1.00 (0.57 to 1.77)

No statistical analyses for this end point

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 2.4g IV

Top of page

End point title

Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 2.4g IV

End point description

Phase 3 (Cohort 1)

End point type

Secondary

End point timeframe

Through day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (2.4g IV) >= 18
Number of subjects analysed	1341	1355
Units: Number of Participants	62	18

No statistical analyses for this end point

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 1.2g IV

Top of page

End point title

Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 1.2g IV

End point description

Phase 3 Cohort 1 - Placebo vs. 1.2 g IV

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 3 Cohort 1 (Placebo) >=18	Phase 3 Cohort 1 (1.2g IV) >= 18
Number of subjects analysed	748	736
Units: Number of Participants	51	20

No statistical analyses for this end point

Secondary: Concentration of REGN10933 + REGN10987 in serum over time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)

Top of page

End point title

Concentration of REGN10933 + REGN10987 in serum over time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)

End point description

Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 3) - Symptomatic Participants [Nominal Sampling Time] = [Clinical Study Time (Visit Day – 1)]

End point type

Secondary

End point timeframe

Up to Nominal Sampling Day 28

End point values	Phase 1 (2.4g IV)	Phase 1 (8.0g IV)	Phase 2 (2.4g IV)	Phase 2 (8.0g IV)	Phase 3 Cohort 1 (1.2g IV)	Phase 3 Cohort 1 (2.4g IV)	Phase 3 Cohort 1 (8.0g IV)	Phase 3 Cohort 3 (1.2g IV)	Phase 3 Cohort 3 (2.4g IV)
Number of subjects analysed	18	21	218	225	491	1214	881	32	24
Units: mg/L
arithmetic mean (standard deviation)
Day 0: EOI n=17,21,194,199,415,1214,881,29,24	594 ± 276	1652 ± 928	701 ± 287	2142 ± 815	415 ± 178	669 ± 236	2239 ± 740	305 ± 80.8	536 ± 165
Day 28 n=18,20,218,225,491,1174,710,32,24	141 ± 97.5	384 ± 143	142 ± 62.5	453 ± 179	85.1 ± 36.9	143 ± 55.1	463 ± 166	63.7 ± 25.9	119 ± 31.1

No statistical analyses for this end point

Secondary: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933+REGN10987 (Phase 1)

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End point title

Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933+REGN10987 (Phase 1)

End point description

Phase 1 Only

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 1 PK-AS
Number of subjects analysed	45
Units: mg/L
arithmetic mean (standard deviation)
2.4g IV n=22	689 ± 391
8.0g IV n=23	1805 ± 720

No statistical analyses for this end point

Secondary: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933+REGN10987 (Phase 1)

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End point title

Assessment of PK parameter: Time to Cmax (tmax) for REGN10933+REGN10987 (Phase 1)

End point description

Phase 1 Only

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 1 PK-AS
Number of subjects analysed	45
Units: day
median (full range (min-max))
2.4g IV (n = 22)	27.7 (0.0847 to 28.2)
8.0g IV (n = 23)	0.0854 (0.0431 to 2.06)

No statistical analyses for this end point

Secondary: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to Day 28 concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)

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End point title

Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to Day 28 concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)

End point description

Phase 1 Only

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 1 PK-AS
Number of subjects analysed	45
Units: day*mg/L
arithmetic mean (standard deviation)
2.4g IV (n = 19)	7158 ± 4255
8.0g IV (n = 20)	19084 ± 5172

No statistical analyses for this end point

Secondary: Immunogenicity as measured by anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

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End point title

Immunogenicity as measured by anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

End point description

Phase 1, Phase 2, Phase 3 (Cohort 1) - Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants

End point type

Secondary

End point timeframe

Through Day 29

End point values	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)	Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)	Phase 3 Cohort 2 (Placebo)	Phase 3 Cohort 2 (1.2g IV)	Phase 3 Cohort 2 (2.4g IV)	Phase 3 Cohort 3 (Placebo)	Phase 3 Cohort 3 (1.2g IV)	Phase 3 Cohort 3 (2.4g IV)
Number of subjects analysed	2353	1935	3087	1170	1	123	64	1	39	33
Units: Participants w/TreatmentEmergentResponse	17	29	20	1	0	1	0	0	0	1

No statistical analyses for this end point

Secondary: Immunogenicity as measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1 - Cohort 3, Ph3 Cohort 1 and Cohort 3)

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End point title

Immunogenicity as measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1 - Cohort 3, Ph3 Cohort 1 and Cohort 3)

End point description

Phase 1, Phase 2, Phase 3 (Cohort 1) - Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants

End point type

Secondary

End point timeframe

Through Day 29

End point values	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (Placebo)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (1.2g IV)	Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4g IV)	Combined Phases 1,2, & 3 Cohort 1 Symptomatic (8.0g IV)	Phase 3 Cohort 2 (Placebo)	Phase 3 Cohort 2 (1.2g IV)	Phase 3 Cohort 2 (2.4g IV)	Phase 3 Cohort 3 (Placebo)	Phase 3 Cohort 3 (1.2g IV)	Phase 3 Cohort 3 (2.4g IV)
Number of subjects analysed	2351	1934	3084	1168	1	123	64	1	39	33
Units: Participants w/TreatmentEmergentResponse	59	56	54	2	0	1	0	0	2	1

No statistical analyses for this end point

Secondary: Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

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End point title

Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

End point description

Phase 2 and Phase 3 (Cohort 1) - Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 3 Cohort 2 (Placebo)	Phase 3 Cohort 2 (1.2g IV)	Phase 3 Cohort 2 (2.4g IV)	Phase 3 Cohort 3 (Placebo)	Phase 3 Cohort 3 (1.2g IV)	Phase 3 Cohort 3 (2.4g IV)
Number of subjects analysed	1	123	64	1	39	33
Units: Participants
TE&TB+;NAb+ Participants	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Immunogenicity as measured by NAbs to REGN10987 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

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End point title

Immunogenicity as measured by NAbs to REGN10987 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

End point description

End point type

Secondary

End point timeframe

Through Day 29

End point values	Phase 3 Cohort 2 (Placebo)	Phase 3 Cohort 2 (1.2g IV)	Phase 3 Cohort 2 (2.4g IV)	Phase 3 Cohort 3 (Placebo)	Phase 3 Cohort 3 (1.2g IV)	Phase 3 Cohort 3 (2.4g IV)
Number of subjects analysed	1	123	64	1	39	33
Units: Participants
TE&TB+;NAb+ Participants	0	1	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose to end of study (approx. 8 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Phase 2 Symptomatic Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic R10933+R10987 8.0g IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 1 Symptomatic Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Symptomatic R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 2 Asymptomatic R10933+R10987 8.0g IV

Reporting group description

8.0g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Asymptomatic Placebo

Reporting group description

Placebo of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection

Reporting group title

Phase 2 Symptomatic R10933+R10987 8.0g IV

Reporting group description

8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19

Reporting group title

Phase 3 Age>=18 Placebo

Reporting group description

Placebo of R10933 + R10987 Participants >=18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18 R10933+R10987 1.2g IV

Reporting group description

1.2g of R10933 + R10987 Participants >=18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18 R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Participants >=18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age>=18 R10933+R10987 8.0g IV

Reporting group description

8.0g of R10933 + R10987 Participants >=18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age<18 Placebo

Reporting group description

Placebo of R10933 + R10987 Participants <18 with COVID-19, not pregnant at randomization

Reporting group title

Phase 3 Age<18 R10933+R10987 1.2g IV

Reporting group description

1.2g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Age<18 R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Participants <18 with COVID-19

Reporting group title

Phase 3 Pregnant Placebo

Reporting group description

Placebo of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant R10933+R10987 1.2g IV

Reporting group description

1.2g of R10933 + R10987 Participants who are pregnant with COVID-19

Reporting group title

Phase 3 Pregnant R10933+R10987 2.4g IV

Reporting group description

2.4g of R10933 + R10987 Participants who are pregnant with COVID-19

Phase 2 Symptomatic Placebo

Phase 1 Symptomatic R10933+R10987 8.0g IV

Phase 1 Symptomatic R10933+R10987 2.4g IV

Phase 1 Symptomatic Placebo

Phase 2 Symptomatic R10933+R10987 2.4g IV

Phase 2 Asymptomatic R10933+R10987 8.0g IV

Phase 2 Asymptomatic R10933+R10987 2.4g IV

Phase 2 Asymptomatic Placebo

Phase 2 Symptomatic R10933+R10987 8.0g IV

Phase 3 Age>=18 Placebo

Phase 3 Age>=18 R10933+R10987 1.2g IV

Phase 3 Age>=18 R10933+R10987 2.4g IV

Phase 3 Age>=18 R10933+R10987 8.0g IV

Phase 3 Age<18 Placebo

Phase 3 Age<18 R10933+R10987 1.2g IV

Phase 3 Age<18 R10933+R10987 2.4g IV

Phase 3 Pregnant Placebo

Phase 3 Pregnant R10933+R10987 1.2g IV

Phase 3 Pregnant R10933+R10987 2.4g IV

Total subjects affected by serious adverse events

subjects affected / exposed

6 / 238 (2.52%)

0 / 23 (0.00%)

1 / 22 (4.55%)

0 / 24 (0.00%)

3 / 236 (1.27%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

2 / 237 (0.84%)

103 / 2347 (4.39%)

39 / 2130 (1.83%)

52 / 3157 (1.65%)

19 / 1012 (1.88%)

0 / 2 (0.00%)

3 / 129 (2.33%)

0 / 71 (0.00%)

0 / 2 (0.00%)

11 / 43 (25.58%)

7 / 35 (20.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric cancer

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Rectal neoplasm

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

1 / 238 (0.42%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

1 / 236 (0.42%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

May-Thurner syndrome

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

Hospitalisation

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

Abnormal labour

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Abortion spontaneous

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ectopic pregnancy

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Foetal growth restriction

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pre-eclampsia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

3 / 43 (6.98%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

deaths causally related to treatment / all

0 / 0

Premature baby

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Premature separation of placenta

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Preterm premature rupture of membranes

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ruptured ectopic pregnancy

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Death

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Fever neonatal

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Impaired healing

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

2 / 2347 (0.09%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

1 / 2130 (0.05%)

2 / 3157 (0.06%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Anaphylactic reaction

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Abnormal uterine bleeding

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory distress syndrome

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Acute respiratory failure

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

5 / 2347 (0.21%)

0 / 2130 (0.00%)

2 / 3157 (0.06%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atelectasis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cough

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

1 / 237 (0.42%)

10 / 2347 (0.43%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 10

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Haemothorax

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

2 / 238 (0.84%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

6 / 2347 (0.26%)

1 / 2130 (0.05%)

2 / 3157 (0.06%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 6

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Interstitial lung disease

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax spontaneous

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary congestion

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

2 / 2130 (0.09%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pulmonary mass

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Respiratory distress

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

2 / 2347 (0.09%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

1 / 129 (0.78%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Bipolar disorder

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Depression

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mental status changes

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Perinatal depression

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Suicidal ideation

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

1 / 129 (0.78%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Continuous glucose monitoring

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Acetabulum fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ankle fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cervical vertebral fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Facial bones fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fall

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fractured sacrum

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal anastomotic stenosis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pelvic fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal compression fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tibia fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper limb fracture

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Anal atresia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Craniosynostosis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Foetal malformation

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Macrocephaly

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tracheo-oesophageal fistula

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Angina pectoris

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

1 / 236 (0.42%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arrhythmia neonatal

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure acute

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure congestive

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cardio-respiratory arrest

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Coronary artery disease

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mitral valve calcification

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Haemorrhagic stroke

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoaesthesia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyporesponsive to stimuli

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Migraine

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune thrombocytopenia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall haematoma

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis ischaemic

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulum

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

1 / 22 (4.55%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peptic ulcer perforation

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Umbilical hernia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

1 / 22 (4.55%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholecystitis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis acute

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia neonatal

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Hyperhidrosis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nephrolithiasis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Renal failure

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary retention

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

1 / 129 (0.78%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Muscular weakness

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rhabdomyolysis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal abscess

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

1 / 237 (0.42%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abscess

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abscess neck

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Appendicitis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacteraemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Breast abscess

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19

subjects affected / exposed

1 / 238 (0.42%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

20 / 2347 (0.85%)

3 / 2130 (0.14%)

9 / 3157 (0.29%)

5 / 1012 (0.49%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 21

0 / 3

1 / 9

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

COVID-19 pneumonia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

2 / 236 (0.85%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

19 / 2347 (0.81%)

5 / 2130 (0.23%)

6 / 3157 (0.19%)

5 / 1012 (0.49%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

1 / 35 (2.86%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 21

0 / 5

0 / 6

0 / 5

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Clostridium difficile colitis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

2 / 2347 (0.09%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Kidney infection

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung abscess

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metapneumovirus pneumonia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

1 / 129 (0.78%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

2 / 238 (0.84%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

19 / 2347 (0.81%)

5 / 2130 (0.23%)

6 / 3157 (0.19%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 20

0 / 5

0 / 6

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pneumonia viral

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

2 / 3157 (0.06%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

2 / 2347 (0.09%)

0 / 2130 (0.00%)

2 / 3157 (0.06%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal bacteraemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

2 / 2347 (0.09%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diabetes mellitus

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diabetes mellitus inadequate control

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gout

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

1 / 2130 (0.05%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

1 / 236 (0.42%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

1 / 3157 (0.03%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

1 / 2347 (0.04%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

3 / 2347 (0.13%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Phase 2 Symptomatic Placebo

Phase 1 Symptomatic R10933+R10987 8.0g IV

Phase 1 Symptomatic R10933+R10987 2.4g IV

Phase 1 Symptomatic Placebo

Phase 2 Symptomatic R10933+R10987 2.4g IV

Phase 2 Asymptomatic R10933+R10987 8.0g IV

Phase 2 Asymptomatic R10933+R10987 2.4g IV

Phase 2 Asymptomatic Placebo

Phase 2 Symptomatic R10933+R10987 8.0g IV

Phase 3 Age>=18 Placebo

Phase 3 Age>=18 R10933+R10987 1.2g IV

Phase 3 Age>=18 R10933+R10987 2.4g IV

Phase 3 Age>=18 R10933+R10987 8.0g IV

Phase 3 Age<18 Placebo

Phase 3 Age<18 R10933+R10987 1.2g IV

Phase 3 Age<18 R10933+R10987 2.4g IV

Phase 3 Pregnant Placebo

Phase 3 Pregnant R10933+R10987 1.2g IV

Phase 3 Pregnant R10933+R10987 2.4g IV

Total subjects affected by non serious adverse events

subjects affected / exposed

2 / 238 (0.84%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

1 / 236 (0.42%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

1 / 237 (0.42%)

16 / 2347 (0.68%)

16 / 2130 (0.75%)

19 / 3157 (0.60%)

4 / 1012 (0.40%)

1 / 2 (50.00%)

0 / 129 (0.00%)

1 / 71 (1.41%)

0 / 2 (0.00%)

5 / 43 (11.63%)

3 / 35 (8.57%)

Pregnancy, puerperium and perinatal conditions

Gestational diabetes

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

0 / 3157 (0.00%)

0 / 1012 (0.00%)

0 / 2 (0.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

2 / 35 (5.71%)

occurrences all number

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 238 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 236 (0.00%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

0 / 237 (0.00%)

0 / 2347 (0.00%)

0 / 2130 (0.00%)

7 / 3157 (0.22%)

1 / 1012 (0.10%)

0 / 2 (0.00%)

0 / 129 (0.00%)

1 / 71 (1.41%)

0 / 2 (0.00%)

3 / 43 (6.98%)

0 / 35 (0.00%)

occurrences all number

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

2 / 238 (0.84%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 24 (0.00%)

1 / 236 (0.42%)

0 / 75 (0.00%)

0 / 74 (0.00%)

0 / 73 (0.00%)

1 / 237 (0.42%)

16 / 2347 (0.68%)

16 / 2130 (0.75%)

12 / 3157 (0.38%)

3 / 1012 (0.30%)

1 / 2 (50.00%)

0 / 129 (0.00%)

0 / 71 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

1 / 35 (2.86%)

occurrences all number

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

03 Jun 2020

Mandatory sequestering is only applicable to patients in the phase 1 sentinel safety group

19 Jun 2020

Grade 3 or 4 treatment-emergent AEs will be collected (phase 1 only)

04 Jul 2020

Virologic efficacy in phase 2 will be assessed using nasopharyngeal (NP) swab samples. Phase 3 secondary endpoints have also been updated for potential inclusion of NP swab samples

11 Jul 2020

Nasal swabs and saliva samples will no longer be collected in phase 2 and are no longer planned for phase 3

08 Aug 2020

Added new cohort of patients in phase 2 to evaluate asymptomatic patients with SARS-CoV-2 infection

20 Nov 2020

Adapt the phase 3 portion of the study and add major adaptations to the patient population, treatment arms, objectives/endpoints, and sample size.

18 Dec 2020

To modify the phase 3 portion of the study in response to health authority feedback

12 Mar 2021

Change in primary and key secondary endpoints

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
09 Jun 2022	Study terminated due to emerging SARS-CoV-2 variants impacting susceptibility to study drug	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants with treatment-emergent serious adverse events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]

Primary: Number of Participants with treatment-emergent serious adverse events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]

Primary: Number of Participants with infusion-related reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

Primary: Number of Participants with infusion-related reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

Primary: Number of participants with hypersensitivity reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

Primary: Number of participants with hypersensitivity reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

Primary: Time-weighted average change from baseline in viral load (log10 copies/mL) from Day 1 to Day 7, as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples (Ph1, Ph2)

Primary: Time-weighted average change from baseline in viral load (log10 copies/mL) from Day 1 to Day 7, as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples (Ph1, Ph2)

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1- 1.2g vs Placebo)

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1- 1.2g vs Placebo)

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1 - 2.4g vs Placebo)

Primary: Proportion of participants with at least one (≥1) COVID-19-related hospitalization or all-cause death (Ph3 Cohort 1 - 2.4g vs Placebo)

Primary: Concentration of REGN10983 + REGN10987 in Serum over time (Ph3 Cohort 2)

Primary: Concentration of REGN10983 + REGN10987 in Serum over time (Ph3 Cohort 2)

Secondary: Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

Secondary: Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

Secondary: Time to COVID-19 symptoms resolution (Ph3 Cohort 1 - 2.4g vs Placebo)

Secondary: Time to COVID-19 symptoms resolution (Ph3 Cohort 1 - 2.4g vs Placebo)

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death from Day 4 through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

Secondary: Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs (Next Phase 2 Cohort)

Secondary: Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs (Next Phase 2 Cohort)

Secondary: Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days (Ph1, Ph2)

Secondary: Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days (Ph1, Ph2)

Secondary: Proportion of participants with ≥1 COVID-19-related medically-attended visit through Day 29 (Ph1, Ph2)

Secondary: Proportion of participants with ≥1 COVID-19-related medically-attended visit through Day 29 (Ph1, Ph2)

Secondary: Proportion of Participants with ≥1 COVID-19 related Hospitalization, Emergency Room, or Urgent Care visit through Day 29 (Ph1, Ph2)

Secondary: Proportion of Participants with ≥1 COVID-19 related Hospitalization, Emergency Room, or Urgent Care visit through Day 29 (Ph1, Ph2)

Secondary: Time to first onset of symptoms consistent with COVID-19 (Phase 2 asymptomatic cohort only)

Secondary: Time to first onset of symptoms consistent with COVID-19 (Phase 2 asymptomatic cohort only)

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 2.4g IV

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 2.4g IV

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 1.2g IV

Secondary: Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death (Ph3 Cohort 1) - Placebo vs. 1.2g IV

Secondary: Concentration of REGN10933 + REGN10987 in serum over time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)

Secondary: Concentration of REGN10933 + REGN10987 in serum over time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)

Secondary: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933+REGN10987 (Phase 1)

Secondary: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933+REGN10987 (Phase 1)

Secondary: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933+REGN10987 (Phase 1)

Secondary: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933+REGN10987 (Phase 1)

Secondary: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to Day 28 concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)

Secondary: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to Day 28 concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)

Secondary: Immunogenicity as measured by anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Secondary: Immunogenicity as measured by anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Secondary: Immunogenicity as measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1 - Cohort 3, Ph3 Cohort 1 and Cohort 3)

Secondary: Immunogenicity as measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1 - Cohort 3, Ph3 Cohort 1 and Cohort 3)

Secondary: Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Secondary: Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Secondary: Immunogenicity as measured by NAbs to REGN10987 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Secondary: Immunogenicity as measured by NAbs to REGN10987 (Ph2 Cohort 1, Ph3 Cohort 1 - Cohort 3)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19