Download PDF

Clinical Trial Results:
A Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-938 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model

Summary
EudraCT number	2018-001878-21
Trial protocol	GB
Global end of trial date	18 Oct 2019

Results information
Results version number	v2(current)
This version publication date	02 Jun 2022
First version publication date	29 Jul 2021
Other versions	v1
Version creation reason	Correction of full data set Updates made to the descriptions of 4 endpoints to align data presentation across registries.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

EDP 938-101

ISRCTN number

US NCT number

NCT03691623

WHO universal trial number (UTN)

Sponsor organisation name

ENANTA Pharmaceuticals, Inc

Sponsor organisation address

500 Arsenal Street, Watertown, MA, United States,

Public contact

Nathalie Adda, ENANTA Pharmaceuticals, Inc, +1 6176070705, nadda@enanta.com

Scientific contact

Nathalie Adda, ENANTA Pharmaceuticals, Inc, +1 6176070705, nadda@enanta.com

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

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?

Analysis stage

Final

Date of interim/final analysis

18 Oct 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Oct 2019

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial was to evaluate the antiviral activity of EDP-938 compared to placebo in healthy adult participants inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b.

Protection of trial subjects

This study was conducted in accordance with the protocol, the guideline for Good Clinical Practice E6(R2), the Declaration of Helsinki, and all applicable local laws and national regulations governing clinical studies.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 179

Worldwide total number of subjects

179

EEA total number of subjects

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)

Adolescents (12-17 years)

Adults (18-64 years)

179

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

A total of 179 participants enrolled in the trial at one site in the United Kingdom from October 2018 to October 2019.

Screening details

For Part 1, 115 participants were inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b of whom 114 were randomized and treated. For Part 2, 64 participants were inoculated with RSV-A Memphis 37b of whom 63 were randomized and treated. Only treated participants are included in the subject disposition and subsequent analyses.

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

Are arms mutually exclusive

Yes

Part 1: EDP-938 600 mg

Arm description

Participants were administered EDP-938 oral suspension once daily (OD) at a dose of 600 mg, followed by a placebo dose 12 hours later (OD). Treatments were administered for a total of 10 doses over 5 days.

Arm type

Experimental

Investigational medicinal product name

EDP-938

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

EDP-938 was administered as a powder for oral suspension.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Placebo was administered as a powder for oral suspension.

Part 1: EDP-938 500 mg then 300 mg

Arm description

Participants were administered EDP-938 oral suspension as a single Loading Dose (LD) of 500 mg followed by a 300 mg dose twice daily (BD) every 12 hours for a total of 10 doses.

Arm type

Experimental

Investigational medicinal product name

EDP-938

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

EDP-938 was administered as a powder for oral suspension.

Part 1: Placebo

Arm description

Participants were administered a placebo dose twice a day (BD) every 12 hours for a total of 10 doses.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Placebo was administered as a powder for oral suspension.

Part 2: EDP-938 600 mg then 300 mg

Arm description

Participants were administered a single loading dose (LD) of 600 mg EDP-938, followed by a 300 mg EDP-938 dose once a day (OD), and with dosing for 5 days.

Arm type

Experimental

Investigational medicinal product name

EDP-938

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

EDP-938 was administered as a powder for oral suspension.

Part 2: EDP-938 400 mg then 200 mg

Arm description

Participants were administered a single loading dose (LD) of 400 mg EDP-938 followed by 200 mg EDP-938 at 12 hours, then 200 mg doses of EDP-938 twice daily (BD), and with dosing for 5 days.

Arm type

Experimental

Investigational medicinal product name

EDP-938

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

EDP-938 was administered as a powder for oral suspension.

Part 2: Placebo

Arm description

Participants were administered a placebo twice daily (BD) for 5 days, with dosing at 12 hour intervals.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Placebo was administered as a powder for oral suspension.

Number of subjects in period 1 ^[1]	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Started	38	38	38	21	21	21
Received treatment	38	38	38	21	21	21
Completed	38	38	38	21	21	21

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: For Part 1, 115 participants were inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b of whom 114 were randomized and treated. For Part 2, 64 participants were inoculated with RSV-A Memphis 37b of whom 63 were randomized and treated. Only treated participants are included in the subject disposition and subsequent analyses.

Baseline characteristics

Top of page

Reporting group title

Part 1: EDP-938 600 mg

Reporting group description

Reporting group title

Part 1: EDP-938 500 mg then 300 mg

Reporting group description

Participants were administered EDP-938 oral suspension as a single Loading Dose (LD) of 500 mg followed by a 300 mg dose twice daily (BD) every 12 hours for a total of 10 doses.

Reporting group title

Part 1: Placebo

Reporting group description

Participants were administered a placebo dose twice a day (BD) every 12 hours for a total of 10 doses.

Reporting group title

Part 2: EDP-938 600 mg then 300 mg

Reporting group description

Participants were administered a single loading dose (LD) of 600 mg EDP-938, followed by a 300 mg EDP-938 dose once a day (OD), and with dosing for 5 days.

Reporting group title

Part 2: EDP-938 400 mg then 200 mg

Reporting group description

Participants were administered a single loading dose (LD) of 400 mg EDP-938 followed by 200 mg EDP-938 at 12 hours, then 200 mg doses of EDP-938 twice daily (BD), and with dosing for 5 days.

Reporting group title

Part 2: Placebo

Reporting group description

Participants were administered a placebo twice daily (BD) for 5 days, with dosing at 12 hour intervals.

Reporting group values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo	Total
Number of subjects	38	38	38	21	21	21	177
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	38	38	38	21	21	21	177
From 65-84 years	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	28.5 ( 5.84 )	27.2 ( 7.50 )	27.6 ( 7.86 )	23.4 ( 3.22 )	24.4 ( 5.83 )	23.1 ( 5.54 )	-
Gender categorical
Units: Subjects
Female	13	18	13	10	11	9	74
Male	25	20	25	11	10	12	103
Race
Units: Subjects
Asian	1	1	2	1	1	0	6
Black or African American	0	1	2	0	1	0	4
White	33	32	31	18	17	19	150
Other	4	4	3	2	2	2	17
Body Mass Index (BMI)
Units: Kilograms per meter squared
arithmetic mean (standard deviation)	24.33 ( 2.853 )	23.27 ( 2.734 )	23.69 ( 2.239 )	23.70 ( 3.399 )	23.66 ( 2.641 )	23.72 ( 2.436 )	-

End points

Top of page

Reporting group title

Part 1: EDP-938 600 mg

Reporting group description

Reporting group title

Part 1: EDP-938 500 mg then 300 mg

Reporting group description

Participants were administered EDP-938 oral suspension as a single Loading Dose (LD) of 500 mg followed by a 300 mg dose twice daily (BD) every 12 hours for a total of 10 doses.

Reporting group title

Part 1: Placebo

Reporting group description

Participants were administered a placebo dose twice a day (BD) every 12 hours for a total of 10 doses.

Reporting group title

Part 2: EDP-938 600 mg then 300 mg

Reporting group description

Participants were administered a single loading dose (LD) of 600 mg EDP-938, followed by a 300 mg EDP-938 dose once a day (OD), and with dosing for 5 days.

Reporting group title

Part 2: EDP-938 400 mg then 200 mg

Reporting group description

Participants were administered a single loading dose (LD) of 400 mg EDP-938 followed by 200 mg EDP-938 at 12 hours, then 200 mg doses of EDP-938 twice daily (BD), and with dosing for 5 days.

Reporting group title

Part 2: Placebo

Reporting group description

Participants were administered a placebo twice daily (BD) for 5 days, with dosing at 12 hour intervals.

Primary: Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load

Top of page

End point title

Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load

End point description

Measured in nasal washes by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in participants inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b.

End point type

Primary

End point timeframe

Twice daily on Day 2 through Day 11 and once on Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: h*log10 copies/milliliter
geometric mean (geometric coefficient of variation)	134.70 ( 85.1 )	113.51 ( 99.9 )	624.30 ( 51.7 )	80.61 ( 112.1 )	160.81 ( 63.3 )	808.28 ( 37.1 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-588.08

Confidence interval

level

95%

sides

2-sided

lower limit

-719.8

upper limit

-456.35

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-564.63

Confidence interval

level

95%

sides

2-sided

lower limit

-689.23

upper limit

-440.02

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-716.08

Confidence interval

level

95%

sides

2-sided

lower limit

-879.92

upper limit

-552.24

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-736.23

Confidence interval

level

95%

sides

2-sided

lower limit

-916.36

upper limit

-556.11

Secondary: Area Under the Curve (AUC) of Total Symptom Score

Top of page

End point title

Area Under the Curve (AUC) of Total Symptom Score

End point description

Total symptom scores (from the 10-item symptom diary card) were used to calculate the AUC. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities: • Runny nose • Stuffy nose • Sneezing • Sore throat • Earache • Malaise (Tiredness) • Cough • Shortness of breath • Headache • Muscle/ joint ache/ stiffness

End point type

Secondary

End point timeframe

Three times daily on Day 0 to Day 11, once on Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: h*score
geometric mean (geometric coefficient of variation)	61.18 ( 347.8 )	37.36 ( 1640.1 )	252.49 ( 243.9 )	26.70 ( 730.2 )	27.81 ( 436.8 )	232.53 ( 530.9 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-355.91

Confidence interval

level

95%

sides

2-sided

lower limit

-506.12

upper limit

-205.69

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-326.64

Confidence interval

level

95%

sides

2-sided

lower limit

-469.68

upper limit

-183.6

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-313.98

Confidence interval

level

95%

sides

2-sided

lower limit

-494.27

upper limit

-133.69

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-312.73

Confidence interval

level

95%

sides

2-sided

lower limit

-508.05

upper limit

-117.4

Secondary: Peak Total Symptom Score

Top of page

End point title

Peak Total Symptom Score

End point description

Peak total symptom score was defined as the highest total symptom score between first dose of study drug and Day 12. Values presented are a sum of individual symptom scores. Total symptom scores at the time of the first dose of study drug can be before or after dosing. Measured by the 10-item Diary Card. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities: • Runny nose • Stuffy nose • Sneezing • Sore throat • Earache • Malaise (Tiredness) • Cough • Shortness of breath • Headache • Muscle/ joint ache/ stiffness

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: h*score
geometric mean (geometric coefficient of variation)	2.3 ( 53.9 )	1.9 ( 89.8 )	4.9 ( 77.9 )	1.6 ( 68.5 )	1.8 ( 55.6 )	4.2 ( 85.8 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

-2

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

-2.4

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

-1.2

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

-0.9

Secondary: Total Symptom Score

Top of page

End point title

Total Symptom Score

End point description

Measured by the 10-item Diary Card. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities: • Runny nose • Stuffy nose • Sneezing • Sore throat • Earache • Malaise (Tiredness) • Cough • Shortness of breath • Headache • Muscle/ joint ache/ stiffness

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25 ^[1]	31 ^[2]	30 ^[3]	15 ^[4]	11 ^[5]	12 ^[6]
Units: Scores on a scale
geometric mean (geometric coefficient of variation)
Relative Day 2 Assessment 1	0.9 ( 97.5 )	0.8 ( 155.4 )	1.9 ( 117.0 )	0.5 ( 140.8 )	0.3 ( 222.5 )	3.0 ( 66.6 )
Relative Day 2 Assessment 2	0.8 ( 94.0 )	0.7 ( 160.3 )	2.4 ( 110.3 )	0.4 ( 185.2 )	0.5 ( 179.8 )	2.9 ( 82.5 )
Relative Day 2 Assessment 3	0.5 ( 117.0 )	0.6 ( 184.4 )	2.7 ( 94.9 )	0.3 ( 196.2 )	0.2 ( 331.7 )	2.6 ( 94.3 )
Relative Day 3 Assessment 1	0.4 ( 137.3 )	0.7 ( 148.5 )	2.6 ( 99.1 )	0.4 ( 166.9 )	0.2 ( 254.2 )	2.2 ( 103.0 )
Relative Day 3 Assessment 2	0.4 ( 144.3 )	0.6 ( 175.2 )	2.7 ( 90.5 )	0.3 ( 207.0 )	0.3 ( 237.1 )	2.3 ( 101.0 )
Relative Day 3 Assessment 3	0.3 ( 190.9 )	0.6 ( 167.7 )	2.5 ( 103.7 )	0.2 ( 332.6 )	0.3 ( 276.4 )	2.2 ( 95.3 )
Relative Day 4 Assessment 1	0.3 ( 177.1 )	0.5 ( 154.9 )	2.3 ( 103.8 )	0.2 ( 343.9 )	0.2 ( 254.2 )	1.9 ( 92.6 )
Relative Day 4 Assessment 2	0.3 ( 186.5 )	0.6 ( 163.1 )	1.8 ( 115.3 )	0.1 ( 387.3 )	0.1 ( 331.7 )	1.7 ( 85.0 )
Relative Day 4 Assessment 3	0.3 ( 263.0 )	0.4 ( 163.5 )	1.8 ( 103.1 )	0.2 ( 280.3 )	0.1 ( 331.7 )	1.8 ( 88.3 )
Relative Day 5 Assessment 1	0.2 ( 228.2 )	0.5 ( 158.9 )	1.6 ( 108.3 )	0.2 ( 244.9 )	0.2 ( 254.2 )	1.6 ( 87.9 )
Relative Day 5 Assessment 2	0.3 ( 191.3 )	0.4 ( 177.1 )	1.4 ( 109.2 )	0.2 ( 314.0 )	0.2 ( 254.2 )	1.4 ( 112.8 )
Relative Day 5 Assessment 3	0.1 ( 364.8 )	0.4 ( 162.0 )	1.3 ( 115.9 )	0.1 ( 280.3 )	0.1 ( 331.7 )	1.4 ( 89.6 )
Relative Day 6 Assessment 1	0.2 ( 300.9 )	0.4 ( 186.9 )	1.2 ( 106.0 )	0.2 ( 314.0 )	0.2 ( 237.1 )	1.5 ( 83.3 )
Relative Day 6 Assessment 2	0.2 ( 288.7 )	0.4 ( 186.9 )	1.0 ( 112.8 )	0.1 ( 387.3 )	0.3 ( 185.4 )	1.2 ( 102.4 )
Relative Day 6 Assessment 3	0.2 ( 280.9 )	0.3 ( 184.6 )	1.0 ( 100.5 )	0.1 ( 387.3 )	0.1 ( 210.8 )	1.1 ( 116.5 )
Relative Day 7 Assessment 1	0.2 ( 225.1 )	0.2 ( 205.3 )	0.7 ( 124.9 )	0.1 ( 387.3 )	0.1 ( 316.2 )	0.8 ( 126.1 )
Relative Day 7 Assessment 2	0.2 ( 196.2 )	0.2 ( 162.0 )	0.7 ( 115.7 )	0.1 ( 346.4 )	0.1 ( 300.0 )	0.9 ( 153.5 )
Relative Day 7 Assessment 3	0.2 ( 291.0 )	0.2 ( 185.8 )	0.9 ( 89.9 )	0.1 ( 331.7 )	0.0 ( 999999 )	0.7 ( 179.2 )
Relative Day 8 Assessment 1	0.1 ( 291.0 )	0.2 ( 199.9 )	0.9 ( 94.9 )	0.1 ( 331.7 )	0.0 ( 999999 )	0.5 ( 153.7 )
Relative Day 8 Assessment 2	0.1 ( 374.2 )	0.1 ( 244.1 )	0.9 ( 99.4 )	0.2 ( 264.6 )	0.0 ( 999999 )	0.2 ( 170.8 )
Relative Day 8 Assessment 3	0.0 ( 999999 )	0.4 ( 149.1 )	0.6 ( 129.1 )	0.0 ( 0.0 )	0.0 ( 999999 )	0.2 ( 200.0 )
Relative Day 9 Assessment 1	0.0 ( 999999 )	0.0 ( 999999 )	0.4 ( 140.5 )	0.0 ( 999999 )	0.0 ( 999999 )	0.2 ( 200.0 )
Relative Day 9 Assessment 2	0.0 ( 999999 )	0.0 ( 999999 )	0.5 ( 91.3 )	0.0 ( 999999 )	0.0 ( 999999 )	0.4 ( 141.4 )

Notes
[1] - n values range from 3-25. 999999 = %CV not calculable as Geometric Mean = 0.0
[2] - n values range from 3-31. 999999 = %CV not calculable as Geometric Mean = 0.0
[3] - n values range from 5-30 (n=30, 29, 24, 23, 19, 17, 10, 5)
[4] - n values range from 4-15. 999999 = %CV not calculable as Geometric Mean = 0.0
[5] - n values range from 0-11. 999999 = %CV not calculable as Geometric Mean = 0.0
[6] - n values range from 2-12 (n=12, 11, 10, 7, 4, 2)

No statistical analyses for this end point

Secondary: Time to Peak Total Symptom Score

Top of page

End point title

Time to Peak Total Symptom Score

End point description

Time to peak total symptom score was defined as the time in days to the highest total symptom score between first dose of study drug and Day 12. Total symptom scores at the time of the first dose of study drug can be before or after dosing.

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: Days
geometric mean (geometric coefficient of variation)	1.18 ( 137.8 )	1.76 ( 110.0 )	2.15 ( 71.4 )	1.45 ( 131.9 )	1.09 ( 136.4 )	1.94 ( 80.5 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-2.09

upper limit

0.44

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.714

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

1.43

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.844

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-2.15

upper limit

1.77

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-3.46

upper limit

0.79

Secondary: Time to Resolution from Peak Total Symptom Score

Top of page

End point title

Time to Resolution from Peak Total Symptom Score

End point description

Time to resolution from peak total symptom score was defined as the time in days from the highest total symptom score (between first dose of study drug and Day 12) until the start of the first 24-hour symptom-free period (after the highest total symptom score). Total symptom scores at the time of the first dose of study drug can be before or after dosing.

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	23	24	30	12	10	11
Units: Days
geometric mean (geometric coefficient of variation)	2.49 ( 70.1 )	2.83 ( 77.5 )	3.30 ( 61.7 )	2.19 ( 70.0 )	1.38 ( 116.5 )	5.17 ( 383 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.145

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-2.37

upper limit

0.36

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.352

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-2.03

upper limit

0.73

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.85

Confidence interval

level

95%

sides

2-sided

lower limit

-4.55

upper limit

-1.15

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.19

upper limit

-1.61

Secondary: Total Weight of Nasal Mucus Produced

Top of page

End point title

Total Weight of Nasal Mucus Produced

End point description

Measured via weighed paper tissues.

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: Weight (g)
arithmetic mean (standard deviation)	12.965 ( 13.0314 )	7.428 ( 11.1324 )	33.416 ( 37.8072 )	2.983 ( 4.4226 )	4.716 ( 6.0015 )	22.391 ( 20.6005 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-24.081

Confidence interval

level

95%

sides

2-sided

lower limit

-36.554

upper limit

-11.607

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-25.954

Confidence interval

level

95%

sides

2-sided

lower limit

-37.695

upper limit

-14.213

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-18.13

Confidence interval

level

95%

sides

2-sided

lower limit

-27.176

upper limit

-9.083

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-19.329

Confidence interval

level

95%

sides

2-sided

lower limit

-29.106

upper limit

-9.552

Secondary: Peak Viral Load

Top of page

End point title

Peak Viral Load

End point description

Peak viral load was defined as the highest quantitative reverse transcription polymerase chain reaction (RT-qPCR) viral load value between first dose of study drug and Day 12. Measured by nasal wash RT-qPCR.

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: log10 copies/mL
arithmetic mean (standard deviation)	4.3552 ( 1.56334 )	4.3111 ( 1.76974 )	6.4727 ( 1.60659 )	3.9718 ( 1.78873 )	4.7727 ( 1.35014 )	7.0973 ( 1.24388 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1292

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8491

upper limit

-1.4093

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1129

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7938

upper limit

-1.4319

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.2191

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1915

upper limit

-2.2467

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.7831

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8522

upper limit

-1.714

Secondary: Time to Peak Viral Load

Top of page

End point title

Time to Peak Viral Load

End point description

Time to peak viral load was defined as the time to the highest quantitative reverse transcription polymerase chain reaction (RT-qPCR) viral load value between first dose of study drug and Day 12. Measured by nasal wash RT-qPCR.

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	31	30	15	11	12
Units: Days
geometric mean (geometric coefficient of variation)	0.74 ( 75.6 )	0.80 ( 130.2 )	2.59 ( 48.5 )	0.88 ( 181.3 )	0.79 ( 64.0 )	3.43 ( 33.7 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.01

Confidence interval

level

95%

sides

2-sided

lower limit

-2.67

upper limit

-1.35

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-1.16

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.98

Confidence interval

level

95%

sides

2-sided

lower limit

-3.43

upper limit

-0.54

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.41

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-0.82

Secondary: Time to Resolution from Peak Viral Load

Top of page

End point title

Time to Resolution from Peak Viral Load

End point description

Time to resolution from peak viral load was defined as the time from peak until first confirmed undetectable assessment between first dose of study drug and Day 12. Measured by by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	30	30	14	11	12
Units: Days
geometric mean (geometric coefficient of variation)	2.03 ( 72.1 )	2.02 ( 79.7 )	4.03 ( 47.5 )	1.67 ( 77.1 )	1.63 ( 43.7 )	3.58 ( 45.6 )

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.04

upper limit

-1.17

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.89

upper limit

-1.11

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.97

Confidence interval

level

95%

sides

2-sided

lower limit

-3.06

upper limit

-0.89

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.46

Confidence interval

level

95%

sides

2-sided

lower limit

-3.64

upper limit

-1.29

Secondary: Time to Cessation of Virus Detection

Top of page

End point title

Time to Cessation of Virus Detection

End point description

Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).

End point type

Secondary

End point timeframe

Day 2 to Day 12

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	25	30	30 ^[7]	14	11	12
Units: Days
median (inter-quartile range (Q1-Q3))	3.5 (2.0 to 4.5)	3.2 (1.5 to 4.5)	8.5 (6.5 to 9.999999)	2.7 (1.5 to 4.0)	2.5 (1.5 to 3.5)	8.5 (7.0 to 9.0)

Notes
[7] - 9.999999=upper quartile is non-estimable as there were too many censored values in the placebo group

Part 1: EDP-938 600mg vs Part 1: Placebo

Comparison groups

Part 1: EDP-938 600 mg v Part 1: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Confidence interval

Part 1:EDP-938 500mg then 300mg vs Part 1: Placebo

Comparison groups

Part 1: Placebo v Part 1: EDP-938 500 mg then 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Confidence interval

Part 2:EDP-938 600mg then 300mg vs Part 2: Placebo

Comparison groups

Part 2: EDP-938 600 mg then 300 mg v Part 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Logrank

Confidence interval

Part 2:EDP-938 400mg then 200mg vs Part 2: Placebo

Comparison groups

Part 2: Placebo v Part 2: EDP-938 400 mg then 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Confidence interval

Secondary: Safety and Tolerability as Assessed by Number of Participants with Treatment-emergent Adverse Events (TEAEs)

Top of page

End point title

Safety and Tolerability as Assessed by Number of Participants with Treatment-emergent Adverse Events (TEAEs)

End point description

A TEAE was defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant physical examinations, vital signs, clinical laboratory tests (including biochemistry, hematology, coagulation [if required], cardiac enzymes and urine analysis), 12-lead electrocardiograms (ECGs) and spirometry results were recorded as AEs. AEs were assessed using the Common Terminology Criteria for Adverse Events (CTCAE); Version 5.0.

End point type

Secondary

End point timeframe

Day 2 to Day 28

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 1: Placebo	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg	Part 2: Placebo
Number of subjects analysed	38	38	38	21	21	21
Units: Number of participants	20	21	21	8	10	11

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) of EDP-938 and its Metabolites

Top of page

End point title

Maximum Plasma Concentration (Cmax) of EDP-938 and its Metabolites ^[8]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[8] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	37	21	20
Units: ng/mL
geometric mean (geometric coefficient of variation)
EDP-938 First Dose	1370 ( 49.7 )	1151 ( 46.9 )	1237.91 ( 33.2 )	800.73 ( 44.9 )
EDP-938 Last Dose	1740 ( 52.8 )	1480 ( 33.4 )	1010 ( 15.9 )	901 ( 27.9 )
EP-024636 First Dose	256 ( 39.3 )	215 ( 41.3 )	264 ( 42.0 )	177 ( 48.2 )
EP-024636 Last Dose	361 ( 34.8 )	342 ( 27.8 )	230 ( 23.0 )	232 ( 32.0 )
EP-024594 First Dose	96.3 ( 48.1 )	76.8 ( 54.8 )	102 ( 61.1 )	72.3 ( 49.1 )
EP-024594 Last Dose	203 ( 32.6 )	240 ( 30.1 )	130 ( 44.1 )	168 ( 32.9 )
EP-024595 First Dose	150 ( 63.2 )	102 ( 79.6 )	167 ( 81.1 )	100 ( 72.1 )
EP-024595 Last Dose	717 ( 45.6 )	1000 ( 49.1 )	499 ( 89.0 )	692 ( 50.5 )

No statistical analyses for this end point

Secondary: Time to Maximum Plasma Concentration (Tmax) of EDP-938 and its Metabolites

Top of page

End point title

Time to Maximum Plasma Concentration (Tmax) of EDP-938 and its Metabolites ^[9]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[9] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	37	21	20
Units: Hours
median (full range (min-max))
EDP-938 First Dose	4.56 (2.0 to 10.0)	5.00 (1.0 to 12.0)	5.80 (1.9 to 10.2)	6.07 (2.0 to 10.2)
EDP-938 Last Dose	4.52 (1.9 to 17.0)	4.10 (0.0 to 10.1)	4.98 (1.0 to 15.9)	4.04 (0.0 to 10.0)
EP-024636 First Dose	5.91 (2.9 to 23.5)	5.97 (2.0 to 12.0)	7.97 (3.1 to 11.9)	6.99 (2.0 to 11.8)
EP-024636 Last Dose	5.00 (2.8 to 15.0)	4.88 (0.5 to 8.0)	6.00 (3.0 to 17.0)	4.04 (0.0 to 8.3)
EP-024594 First Dose	10.07 (4.1 to 24.1)	10.23 (4.0 to 12.0)	11.83 (6.2 to 23.8)	10.14 (4.9 to 11.9)
EP-024594 Last Dose	8.07 (4.0 to 20.1)	4.98 (0.0 to 12.0)	8.00 (0.5 to 17.2)	5.03 (0.0 to 8.3)
EP-024595 First Dose	23.72 (8.0 to 24.1)	11.85 (8.0 to 12.2)	23.75 (11.8 to 24.0)	11.83 (5.8 to 12.0)
EP-024595 Last Dose	10.90 (3.0 to 22.0)	5.07 (0.4 to 12.0)	11.88 (2.8 to 22.3)	4.04 (0.0 to 9.9)

No statistical analyses for this end point

Secondary: Terminal Phase Half-Life (t1/2) of EDP-938 and its Metabolites

Top of page

End point title

Terminal Phase Half-Life (t1/2) of EDP-938 and its Metabolites ^[10]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[10] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	35	21	20
Units: Hours
geometric mean (geometric coefficient of variation)
EDP-938	14.5 ( 25.4 )	13.8 ( 27.4 )	14.5 ( 31.3 )	13.7 ( 23.5 )
EP-024636	14.5 ( 21.5 )	13.4 ( 21.1 )	14.4 ( 29.8 )	13.5 ( 21.2 )
EP-024594	17.8 ( 18.2 )	16.2 ( 18.5 )	17.5 ( 25.1 )	15.4 ( 17.0 )
EP-024595	28.5 ( 38.2 )	25.5 ( 25.1 )	22.7 ( 15.6 )	23.0 ( 19.4 )

No statistical analyses for this end point

Secondary: Apparent Systemic Clearance (CLss/F) of EDP-938

Top of page

End point title

Apparent Systemic Clearance (CLss/F) of EDP-938 ^[11]

End point description

CLss/F is presented instead of CL/F.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[11] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	35	21	20
Units: litres per hour
geometric mean (geometric coefficient of variation)
EDP-938	26.9 ( 44.8 )	24.1 ( 28.4 )	21.3 ( 17.6 )	25.0 ( 23.9 )

No statistical analyses for this end point

Secondary: Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (λz) of EDP-938 and its Metabolites

Top of page

End point title

Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (λz) of EDP-938 and its Metabolites ^[12]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[12] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	35	21	20
Units: 1/hour
geometric mean (geometric coefficient of variation)
EDP-938	0.05 ( 1.2 )	0.05 ( 1.6 )	0.05 ( 1.5 )	0.05 ( 1.2 )
EP-024636	0.05 ( 1.1 )	0.05 ( 1.2 )	0.05 ( 1.3 )	0.05 ( 1.1 )
EP-024594	0.04 ( 0.7 )	0.04 ( 0.8 )	0.04 ( 1.0 )	0.05 ( 0.8 )
EP-024595	0.03 ( 1.3 )	0.03 ( 0.9 )	0.03 ( 0.5 )	0.03 ( 0.6 )

No statistical analyses for this end point

Secondary: Volume of Distribution at Steady State (Vss/F) of EDP-938

Top of page

End point title

Volume of Distribution at Steady State (Vss/F) of EDP-938 ^[13]

End point description

Vss/F is presented instead of Vd/F.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[13] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	35	21	20
Units: litre(s)
geometric mean (geometric coefficient of variation)
EDP-938	560 ( 42.8 )	476 ( 23.1 )	442 ( 24.1 )	491 ( 28.8 )

No statistical analyses for this end point

Secondary: Plasma Concentration at 12 Hours (C12) of EDP-938 and its Metabolites

Top of page

End point title

Plasma Concentration at 12 Hours (C12) of EDP-938 and its Metabolites ^[14]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. Data were specifically collected for BID dosing groups at the specified times.

End point type

Secondary

End point timeframe

Day 2, Day 6 and Day 7; 12 hours post-dose

Notes
[14] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	0 ^[15]	37	0 ^[16]	20
Units: Nanograms per milliliter
geometric mean (geometric coefficient of variation)
EDP-938 First Dose	( )	679.35 ( 34.5 )	( )	565.60 ( 39.5 )
EDP-938 Last Dose	( )	822 ( 35.2 )	( )	525 ( 30.0 )
EP-024636 First Dose	( )	168 ( 32.1 )	( )	149 ( 41.0 )
EP-024636 Last Dose	( )	228 ( 27.8 )	( )	153 ( 28.9 )
EP-024594 First Dose	( )	75.3 ( 54.4 )	( )	68.8 ( 50.8 )
EP-024594 Last Dose	( )	188 ( 27.4 )	( )	133 ( 31.7 )
EP-024595 First Dose	( )	100 ( 79.6 )	( )	99.3 ( 75.4 )
EP-024595 Last Dose	( )	705 ( 39.1 )	( )	515 ( 40.2 )

Notes
[15] - C12 is reported for twice daily (BD) dosing groups only.
[16] - C12 is reported for twice daily (BD) dosing groups only.

No statistical analyses for this end point

Secondary: Plasma Concentration at 24 Hours (C24) of EDP-938 and its Metabolites

Top of page

End point title

Plasma Concentration at 24 Hours (C24) of EDP-938 and its Metabolites ^[17]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. Data were specifically collected for OD dosing groups at the specified times.

End point type

Secondary

End point timeframe

Day 7; 24 hours post-dose

Notes
[17] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	37	0 ^[18]	21	0 ^[19]
Units: Nanograms per milliliter
geometric mean (geometric coefficient of variation)
EDP-938 First Dose	404 ( 46.9 )	( )	453 ( 31.6 )	( )
EDP-938 Last Dose	491 ( 56.4 )	( )	287 ( 74.0 )	( )
EP-024636 First Dose	121 ( 43.5 )	( )	136 ( 30.5 )	( )
EP-024636 Last Dose	148 ( 44.4 )	( )	88.3 ( 64.8 )	( )
EP-024594 First Dose	78.8 ( 43.7 )	( )	87.8 ( 56.0 )	( )
EP-024594 Last Dose	127 ( 29.3 )	( )	74.5 ( 72.4 )	( )
EP-024595 First Dose	142 ( 57.5 )	( )	163 ( 79.4 )	( )
EP-024595 Last Dose	461 ( 41.6 )	( )	287 ( 93.8 )	( )

Notes
[18] - C24 is reported for once daily (OD) dosing groups relative to last dose.
[19] - C24 is reported for once daily (OD) dosing groups relative to last dose.

No statistical analyses for this end point

Secondary: Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and its Metabolites

Top of page

End point title

Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and its Metabolites ^[20]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[20] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	37	21	20
Units: Nanogram hours per mililitre
geometric mean (geometric coefficient of variation)
EDP-938 First Dose	16730 ( 47.0 )	7540 ( 45.8 )	16420 ( 24.0 )	5970 ( 40.5 )
EDP-938 Last Dose	32000 ( 52.9 )	27300 ( 40.8 )	20500 ( 32.1 )	17800 ( 29.0 )
EP-024636 First Dose	3800 ( 42.9 )	1490 ( 49.3 )	4080 ( 36.2 )	1300 ( 45.9 )
EP-024636 Last Dose	8680 ( 42.9 )	7690 ( 32.8 )	5550 ( 24.1 )	5180 ( 28.8 )
EP-024594 First Dose	1610 ( 55.3 )	512 ( 73.1 )	1740 ( 64.2 )	487 ( 51.5 )
EP-024594 Last Dose	6880 ( 31.7 )	7160 ( 27.5 )	4320 ( 37.3 )	4990 ( 31.6 )
EP-024595 First Dose	2510 ( 72.1 )	540 ( 95.6 )	2420 ( 83.1 )	541 ( 67.1 )
EP-024595 Last Dose	29600 ( 40.5 )	36900 ( 38.4 )	19700 ( 77.1 )	25800 ( 46.6 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and its Metabolites

Top of page

End point title

Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and its Metabolites ^[21]

End point description

The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.

End point type

Secondary

End point timeframe

Day 2 to Day 6: Pre-dose; Day 2 and Day 6: 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose, and Day 7 only: 15, 24, 30, 36, 48, 60 and 72 hours post-dose

Notes
[21] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	35	21	20
Units: Nanogram hours per mililitre
geometric mean (geometric coefficient of variation)
EDP-938	22300 ( 46.5 )	12500 ( 29.7 )	14100 ( 18.5 )	8010 ( 24.9 )
EP-024636	5770 ( 36.1 )	3270 ( 25.2 )	3640 ( 24.5 )	2210 ( 30.8 )
EP-024594	3830 ( 30.6 )	2470 ( 26.1 )	2410 ( 45.4 )	1710 ( 33.8 )
EP-024595	12100 ( 41.9 )	8950 ( 36.7 )	8350 ( 82.0 )	6210 ( 44.3 )

No statistical analyses for this end point

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC

Top of page

End point title

Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC ^[22]

End point description

The overall criteria to define correlation was based on identifying a PK AUC associated with a less favorable viral load AUC i.e. a low PK AUC and a high viral load AUC indicated a correlation.

End point type

Secondary

End point timeframe

Day 2 to Day 18

Notes
[22] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	38	21	21
Units: Number of participants	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC

Top of page

End point title

Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC ^[23]

End point description

The overall criteria to define correlation was based on identifying a PK AUC associated with a less favorable TSS AUC, i.e. a low PK AUC and a high TSS AUC indicated a correlation.

End point type

Secondary

End point timeframe

Day 2 to Day 18

Notes
[23] - 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: Pharmacokinetic data is only presented for arms where participants received the investigational product (EDP-938), and not for placebo arms.

End point values	Part 1: EDP-938 600 mg	Part 1: EDP-938 500 mg then 300 mg	Part 2: EDP-938 600 mg then 300 mg	Part 2: EDP-938 400 mg then 200 mg
Number of subjects analysed	38	38	21	21
Units: Number of participants	0	0	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Day 2 to Day 28

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Part 1: EDP-938 600mg

Reporting group description

Participants received EDP-938 oral suspension at 600 mg followed after 12 hours by a placebo dose on each of 5 days of dosing for a total of 10 doses.

Reporting group title

Part 1: EDP-938 500mg then 300mg

Reporting group description

Participants received EDP-938 oral suspension as a single Loading Dose (LD) of 500 mg followed by 300 mg dose twice daily (BD) (every 12 hours) for a total of 10 doses.

Reporting group title

Part 1: Placebo

Reporting group description

Participants received placebo dose twice a day (BD) (every 12 hours) for a total of 10 doses.

Reporting group title

Part 2: EDP-938 600mg then 300mg

Reporting group description

Participants received a single Loading Dose (LD) of 600 mg EDP-938, followed by a 300 mg EDP-938 dose once a day (OD), and with dosing for 5 days. Participants also received placebo OD to mimic the twice daily (BD) dosing group.

Reporting group title

Part 2: EDP-938 400mg then 200mg

Reporting group description

Participants received a single Loading Dose (LD) of 400 mg EDP-938 followed by 200 mg EDP-938 at 12 hours, then 200 mg doses of EDP-938 twice daily (BD), and with dosing for 5 days.

Reporting group title

Part 2: Placebo

Reporting group description

Participants received placebo twice daily (BD) for 5 days, with dosing at 12 hours intervals.

Serious adverse events	Part 1: EDP-938 600mg	Part 1: EDP-938 500mg then 300mg	Part 1: Placebo	Part 2: EDP-938 600mg then 300mg	Part 2: EDP-938 400mg then 200mg	Part 2: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Part 1: EDP-938 600mg	Part 1: EDP-938 500mg then 300mg	Part 1: Placebo	Part 2: EDP-938 600mg then 300mg	Part 2: EDP-938 400mg then 200mg	Part 2: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	20 / 38 (52.63%)	21 / 38 (55.26%)	21 / 38 (55.26%)	8 / 21 (38.10%)	10 / 21 (47.62%)	11 / 21 (52.38%)
General disorders and administration site conditions
Catheter site related reaction
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	2 / 38 (5.26%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	2	0	0	0
Chest discomfort
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	1	0	0	0
Pyrexia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	1	0	0
Thirst
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0
Vessel puncture site haematoma
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0
Vessel puncture site pain
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	0
Feeling hot
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Vessel puncture site paraesthesia
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	1	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	1	0
Throat irritation
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Nasal congestion
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	2 / 38 (5.26%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	2	2	0	0	0
Forced expiratory volume decreased
subjects affected / exposed	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	3	1	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
FEV1/FVC ratio decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Forced vital capacity decreased
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0
Soft tissue injury
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 38 (10.53%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	2 / 21 (9.52%)	1 / 21 (4.76%)
occurrences all number	4	0	1	0	2	1
Headache
subjects affected / exposed	4 / 38 (10.53%)	1 / 38 (2.63%)	3 / 38 (7.89%)	0 / 21 (0.00%)	1 / 21 (4.76%)	2 / 21 (9.52%)
occurrences all number	5	2	3	0	1	2
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	2 / 38 (5.26%)	0 / 21 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	1	2	0	1	0
Hypoacusis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0
Eye disorders
Blepharospasm
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	2	0	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 38 (0.00%)	2 / 38 (5.26%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	2	1	0	0	1
Diarrhoea
subjects affected / exposed	3 / 38 (7.89%)	3 / 38 (7.89%)	0 / 38 (0.00%)	1 / 21 (4.76%)	1 / 21 (4.76%)	0 / 21 (0.00%)
occurrences all number	3	3	0	1	1	0
Dyspepsia
subjects affected / exposed	1 / 38 (2.63%)	2 / 38 (5.26%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	2	0	0	0	0
Haemorrhoids
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 38 (2.63%)	1 / 38 (2.63%)	3 / 38 (7.89%)	1 / 21 (4.76%)	3 / 21 (14.29%)	0 / 21 (0.00%)
occurrences all number	1	1	3	1	3	0
Vomiting
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	2	0	0
Abdominal discomfort
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Abdominal tenderness
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	1	0	0
Rash
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	2	0	0	1
Rash papular
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0
Skin irritation
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	2	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Petechiae
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin mass
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Micturition urgency
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	1	0	0	0
Muscle spasms
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	2	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	2 / 21 (9.52%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	2	0
Neck pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Infections and infestations
Angular cheilitis
subjects affected / exposed	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	1	0	0	0
Herpes simplex
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 38 (5.26%)	2 / 38 (5.26%)	4 / 38 (10.53%)	1 / 21 (4.76%)	2 / 21 (9.52%)	1 / 21 (4.76%)
occurrences all number	2	2	4	1	2	1
Viral upper respiratory tract infection
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)	2 / 21 (9.52%)	0 / 21 (0.00%)
occurrences all number	1	0	1	0	2	0
Urinary tract infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0
Viral tonsillitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 38 (2.63%)	0 / 38 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)	0 / 21 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	2	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Sep 2018

Amendment 1, dated 4 September 2018 (protocol version 2.0), revised the protocol in line with MHRA recommendations/requests included in the Response to Grounds for Non-Acceptance letter dated 24 August 2018: • Section 7.3: Inclusion criterion #4 updated to reduce BMI upper limit of 30 kg/m^2 • Section 7.3: Inclusion criterion #5 on contraception updated to align with contraceptive methods in the Clinical Trials Facilitation Group (GTFG) guidance. • Section 18.5.1: Stopping criteria for the study updated to provide definitive stopping criteria information and Table 18.1 This amendment also clarified PK blood sampling for Dose 9, 12-hours post dose sample, and dose 10, pre-dose. The SME abbreviation was also clarified (=Sponsor’s Medical Expert).

30 Oct 2018

Amendment 2, dated 30 October 2018 (protocol version 3.0), included a change in the Principal Investigator (PI). The Study Personnel Contact List was updated with PI contact details. The 72 h PK plasma sample collection for participants who started dosing on the afternoon of Day 5 post viral challenge was clarified. This amendment also clarified the rescreening process for participants who were found ineligible based on review of eligibility criteria.

11 Jul 2019

Amendment 3, dated 11 July 2019 (protocol version 4.0), included a change in the Principal Investigator (PI). The Study Personnel Contact List was updated with PI contact details. This amendment confirmed the treatment groups for Part 2 in the light of the emerging data from Part 1. Due to the combination in dosing schedule (i.e., OD and BD), all participants were treated twice daily (similar to Part 1) in order to maintain the blind between treatment groups. The duration of dosing for Part 2 was clarified as a 5 days dosing regimen. The number of participants enrolled in each of the treatment groups for Part 2 was confirmed as n=21 participants per treatment group. The randomization ratio for Part 2 was clarified as a 1:1:1 ratio. The PK blood sampling schedule for Part 2 was clarified as was the adverse events reporting for 15% drop in spirometry.

Were there any global interruptions to the trial? No

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

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-938 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load

Primary: Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load

Secondary: Area Under the Curve (AUC) of Total Symptom Score

Secondary: Area Under the Curve (AUC) of Total Symptom Score

Secondary: Peak Total Symptom Score

Secondary: Peak Total Symptom Score

Secondary: Total Symptom Score

Secondary: Total Symptom Score

Secondary: Time to Peak Total Symptom Score

Secondary: Time to Peak Total Symptom Score

Secondary: Time to Resolution from Peak Total Symptom Score

Secondary: Time to Resolution from Peak Total Symptom Score

Secondary: Total Weight of Nasal Mucus Produced

Secondary: Total Weight of Nasal Mucus Produced

Secondary: Peak Viral Load

Secondary: Peak Viral Load

Secondary: Time to Peak Viral Load

Secondary: Time to Peak Viral Load

Secondary: Time to Resolution from Peak Viral Load

Secondary: Time to Resolution from Peak Viral Load

Secondary: Time to Cessation of Virus Detection

Secondary: Time to Cessation of Virus Detection

Secondary: Safety and Tolerability as Assessed by Number of Participants with Treatment-emergent Adverse Events (TEAEs)

Secondary: Safety and Tolerability as Assessed by Number of Participants with Treatment-emergent Adverse Events (TEAEs)

Secondary: Maximum Plasma Concentration (Cmax) of EDP-938 and its Metabolites

Secondary: Maximum Plasma Concentration (Cmax) of EDP-938 and its Metabolites

Secondary: Time to Maximum Plasma Concentration (Tmax) of EDP-938 and its Metabolites

Secondary: Time to Maximum Plasma Concentration (Tmax) of EDP-938 and its Metabolites

Secondary: Terminal Phase Half-Life (t1/2) of EDP-938 and its Metabolites

Secondary: Terminal Phase Half-Life (t1/2) of EDP-938 and its Metabolites

Secondary: Apparent Systemic Clearance (CLss/F) of EDP-938

Secondary: Apparent Systemic Clearance (CLss/F) of EDP-938

Secondary: Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (λz) of EDP-938 and its Metabolites

Secondary: Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (λz) of EDP-938 and its Metabolites

Secondary: Volume of Distribution at Steady State (Vss/F) of EDP-938

Secondary: Volume of Distribution at Steady State (Vss/F) of EDP-938

Secondary: Plasma Concentration at 12 Hours (C12) of EDP-938 and its Metabolites

Secondary: Plasma Concentration at 12 Hours (C12) of EDP-938 and its Metabolites

Secondary: Plasma Concentration at 24 Hours (C24) of EDP-938 and its Metabolites

Secondary: Plasma Concentration at 24 Hours (C24) of EDP-938 and its Metabolites

Secondary: Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and its Metabolites

Secondary: Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and its Metabolites

Secondary: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and its Metabolites

Secondary: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and its Metabolites

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC

Secondary: Number of Participants with Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-938 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model