RSV Infection
Conditions
Keywords
challenge study, RSV, antiviral, RSV-A Memphis 37b
Brief summary
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 in healthy subjects infected with RSV-A Memphis 37b. This study is designed to compare the antiviral effect of EDP-938 compared to a placebo control in the respiratory syncytial virus challenge model.
Interventions
DRUGEDP-938 Dose 1
Oral suspension for 5 days
DRUGEDP-938 Dose 2
Oral suspension for 5 days
DRUGPlacebo
Oral suspension for 5 days
DRUGEDP-938 Dose 3
Oral suspension for 5 days
DRUGEDP-938 Dose 4
Oral suspension for 5 days
Sponsors
hVIVO Services Limited
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* An informed consent document signed and dated by the subject * Age 18 to 55 years, inclusive * In good health with no history of major medical conditions * A total body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m\^2 and ≤ 30kg/m\^2
Exclusion criteria
* Pregnant or nursing females * Acute or chronic medical illness * Abnormal lung function * Positive for human immunodeficiency virus (HIV), active hepatitis A, B or C test * Nose or nasopharynx abnormalities * Receipt of any investigational drug within 3 months prior to the planned date of viral challenge/first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | Twice daily on Day 2 through Day 11 and once on Day 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Total Symptom Score | Day 2 to Day 12 | 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, with a potential range of 0 (best) to 30 (worst). 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 |
| Total Symptom Score | Day 2 to Day 9 | 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. Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise (Tiredness) * Cough * Shortness of breath * Headache * Muscle/ joint ache/ stiffness |
| Time to Peak Total Symptom Score | Day 2 to Day 12 | 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. |
| Time to Resolution From Peak Total Symptom Score | Day 2 to Day 12 | 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. |
| Total Weight of Nasal Mucus Produced | Day 2 to Day 12 | Measured via weighed paper tissues and reported as a mean total across all study days. |
| Peak Viral Load | Day 2 to Day 12 | 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. |
| Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC | Day 2 to Day 18 | 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. |
| Time to Peak Viral Load | Day 2 to Day 12 | 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. |
| Time to Resolution From Peak Viral Load | Day 2 to Day 12 | 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). |
| Time to Cessation of Virus Detection | Day 2 to Day 12 | Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR). |
| Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 2 to Day 28 | 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 adverse events. |
| Area Under the Curve (AUC) of Total Symptom Score | Three times daily on Day 0 to Day 11, once on Day 12 | Total symptom scores (from the 10-item 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 Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). Data presented is hours x score. |
| Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | — |
| 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 | Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Volume of Distribution at Steady State (Vss/F) of EDP-938 | Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | — |
| Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | Day 2 and Day 7; 12 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | Day 2 and Day 7; 24 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
| Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC | Day 2 to Day 18 | 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. |
| Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 179 participants enrolled in the trial at one site in the United Kingdom from October 2018 to October 2019.
Pre-assignment details
For Part 1, 115 participants were inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b and randomized, of whom 114 were treated. For Part 2, 64 participants were inoculated with RSV-A Memphis 37b of whom 63 were randomized and treated. The 178 randomized participants are included in the participant flow. One inoculated participant was not randomized to a specific treatment assignment and is not included in participant flow.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: EDP-938 600 mg Participants were administered EDP-938 oral suspension of 600 mg followed after 12 hours by a placebo once daily (OD) for a total of 10 doses over 5 days. | 38 |
| Part 1: EDP-938 500 mg Then 300 mg Participants were administered EDP-938 oral suspension as a single loading dose of 500 mg followed after 12 hours by EDP-938 300 mg twice daily (BID) (every 12 hours) for a total of 10 doses over 5 days. | 38 |
| Part 1: Placebo Participants were administered a placebo BID (every 12 hours) for a total of 10 doses over 5 days. | 38 |
| Part 2: EDP-938 600 mg Then 300 mg Participants were administered a single loading dose of 600 mg EDP-938, followed by EDP-938 300 mg OD, and with dosing for 5 days. | 21 |
| Part 2: EDP-938 400 mg Then 200 mg Participants were administered a single loading dose of 400 mg EDP-938 followed by EDP-938 200 mg at 12 hours, then EDP-938 200 mg BID, and with dosing for 5 days. | 21 |
| Part 2: Placebo Participants were administered a placebo BID for 5 days, with dosing at 12 hour intervals. | 21 |
| Total | 177 |
Baseline characteristics
| Characteristic | Part 1: EDP-938 600 mg | Part 1: EDP-938 500 mg Then 300 mg | Part 1: Placebo | Part 2: EDP-938 400 mg Then 200 mg | Part 2: EDP-938 600 mg Then 300 mg | Part 2: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 38 Participants | 38 Participants | 21 Participants | 21 Participants | 21 Participants | 177 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) White | 33 Participants | 32 Participants | 31 Participants | 17 Participants | 18 Participants | 19 Participants | 150 Participants |
| Sex: Female, Male Female | 13 Participants | 18 Participants | 13 Participants | 11 Participants | 10 Participants | 9 Participants | 74 Participants |
| Sex: Female, Male Male | 25 Participants | 20 Participants | 25 Participants | 10 Participants | 11 Participants | 12 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 38 | 0 / 38 | 0 / 21 | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 20 / 38 | 21 / 38 | 21 / 38 | 8 / 21 | 10 / 21 | 11 / 21 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 | 0 / 38 | 0 / 21 | 0 / 21 | 0 / 21 |
Outcome results
Primary
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
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.
Time frame: Twice daily on Day 2 through Day 11 and once on Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 134.70 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 85.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 113.51 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 99.9 |
| Part 1: Placebo | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 624.30 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 51.7 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 80.61 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 112.1 |
| Part 2: EDP-938 400 mg Then 200 mg | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 160.81 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 63.3 |
| Part 2: Placebo | Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | 808.28 hours*log10 copies/milliliter (mL) | Geometric Coefficient of Variation 37.1 |
p-value: <0.00195% CI: [-719.8, -456.35]ANCOVA
p-value: <0.00195% CI: [-689.23, -440.02]ANCOVA
p-value: <0.00195% CI: [-879.92, -552.24]ANCOVA
p-value: <0.00195% CI: [-916.36, -556.11]ANCOVA
Secondary
Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | 26.9 litres per hour | Geometric Coefficient of Variation 44.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | 24.1 litres per hour | Geometric Coefficient of Variation 28.4 |
| Part 1: Placebo | Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | 21.3 litres per hour | Geometric Coefficient of Variation 17.6 |
| Part 2: EDP-938 600 mg Then 300 mg | Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | 25.0 litres per hour | Geometric Coefficient of Variation 23.9 |
Secondary
Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 First Dose | 1610 ng*hr/mL | Geometric Coefficient of Variation 55.3 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 32000 ng*hr/mL | Geometric Coefficient of Variation 52.9 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 8680 ng*hr/mL | Geometric Coefficient of Variation 42.9 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 First Dose | 3800 ng*hr/mL | Geometric Coefficient of Variation 42.9 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 29600 ng*hr/mL | Geometric Coefficient of Variation 40.5 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 First Dose | 16730 ng*hr/mL | Geometric Coefficient of Variation 47 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 First Dose | 2510 ng*hr/mL | Geometric Coefficient of Variation 72.1 |
| Part 1: EDP-938 600 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 6880 ng*hr/mL | Geometric Coefficient of Variation 31.7 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 27300 ng*hr/mL | Geometric Coefficient of Variation 40.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 First Dose | 1490 ng*hr/mL | Geometric Coefficient of Variation 49.3 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 First Dose | 7540 ng*hr/mL | Geometric Coefficient of Variation 45.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 7690 ng*hr/mL | Geometric Coefficient of Variation 32.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 First Dose | 512 ng*hr/mL | Geometric Coefficient of Variation 73.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 7160 ng*hr/mL | Geometric Coefficient of Variation 27.5 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 First Dose | 540 ng*hr/mL | Geometric Coefficient of Variation 95.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 36900 ng*hr/mL | Geometric Coefficient of Variation 38.4 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 First Dose | 16420 ng*hr/mL | Geometric Coefficient of Variation 24 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 19700 ng*hr/mL | Geometric Coefficient of Variation 77.1 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 First Dose | 2420 ng*hr/mL | Geometric Coefficient of Variation 83.1 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 First Dose | 1740 ng*hr/mL | Geometric Coefficient of Variation 64.2 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 First Dose | 4080 ng*hr/mL | Geometric Coefficient of Variation 36.2 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 4320 ng*hr/mL | Geometric Coefficient of Variation 37.3 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 5550 ng*hr/mL | Geometric Coefficient of Variation 24.1 |
| Part 1: Placebo | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 20500 ng*hr/mL | Geometric Coefficient of Variation 32.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 5180 ng*hr/mL | Geometric Coefficient of Variation 28.8 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 First Dose | 487 ng*hr/mL | Geometric Coefficient of Variation 51.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 25800 ng*hr/mL | Geometric Coefficient of Variation 46.6 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 4990 ng*hr/mL | Geometric Coefficient of Variation 31.6 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 17800 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024636 First Dose | 1300 ng*hr/mL | Geometric Coefficient of Variation 45.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EP-024595 First Dose | 541 ng*hr/mL | Geometric Coefficient of Variation 67.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites | EDP-938 First Dose | 5970 ng*hr/mL | Geometric Coefficient of Variation 40.5 |
Secondary
Area Under the Curve (AUC) of Total Symptom Score
Total symptom scores (from the 10-item 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 Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). Data presented is hours x score.
Time frame: Three times daily on Day 0 to Day 11, once on Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Area Under the Curve (AUC) of Total Symptom Score | 61.18 hours*score | Geometric Coefficient of Variation 347.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Curve (AUC) of Total Symptom Score | 37.36 hours*score | Geometric Coefficient of Variation 1640.1 |
| Part 1: Placebo | Area Under the Curve (AUC) of Total Symptom Score | 252.49 hours*score | Geometric Coefficient of Variation 243.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Curve (AUC) of Total Symptom Score | 26.70 hours*score | Geometric Coefficient of Variation 730.2 |
| Part 2: EDP-938 400 mg Then 200 mg | Area Under the Curve (AUC) of Total Symptom Score | 27.81 hours*score | Geometric Coefficient of Variation 436.8 |
| Part 2: Placebo | Area Under the Curve (AUC) of Total Symptom Score | 232.53 hours*score | Geometric Coefficient of Variation 530.9 |
p-value: <0.00195% CI: [-506.12, -205.69]ANCOVA
p-value: <0.00195% CI: [-469.68, -183.6]ANCOVA
p-value: =0.00195% CI: [-494.27, -133.69]ANCOVA
p-value: =0.00395% CI: [-508.05, -117.4]ANCOVA
Secondary
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EDP-938 | 22300 ng*hr/mL | Geometric Coefficient of Variation 46.5 |
| Part 1: EDP-938 600 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024636 | 5770 ng*hr/mL | Geometric Coefficient of Variation 36.1 |
| Part 1: EDP-938 600 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024594 | 3830 ng*hr/mL | Geometric Coefficient of Variation 30.6 |
| Part 1: EDP-938 600 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024595 | 12100 ng*hr/mL | Geometric Coefficient of Variation 41.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024636 | 3270 ng*hr/mL | Geometric Coefficient of Variation 25.2 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024594 | 2470 ng*hr/mL | Geometric Coefficient of Variation 26.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024595 | 8950 ng*hr/mL | Geometric Coefficient of Variation 36.7 |
| Part 1: EDP-938 500 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EDP-938 | 12500 ng*hr/mL | Geometric Coefficient of Variation 29.7 |
| Part 1: Placebo | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024594 | 2410 ng*hr/mL | Geometric Coefficient of Variation 45.4 |
| Part 1: Placebo | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024636 | 3640 ng*hr/mL | Geometric Coefficient of Variation 24.5 |
| Part 1: Placebo | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024595 | 8350 ng*hr/mL | Geometric Coefficient of Variation 82 |
| Part 1: Placebo | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EDP-938 | 14100 ng*hr/mL | Geometric Coefficient of Variation 18.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024595 | 6210 ng*hr/mL | Geometric Coefficient of Variation 44.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024636 | 2210 ng*hr/mL | Geometric Coefficient of Variation 30.8 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EDP-938 | 8010 ng*hr/mL | Geometric Coefficient of Variation 24.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites | EP-024594 | 1710 ng*hr/mL | Geometric Coefficient of Variation 33.8 |
Secondary
Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 1370 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.7 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 1740 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.8 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 256 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.3 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 361 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.8 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 96.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.1 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 203 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.6 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 150 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63.2 |
| Part 1: EDP-938 600 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 717 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 240 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 76.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 1480 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.4 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 1000 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 102 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 342 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 215 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.3 |
| Part 1: EDP-938 500 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 1151 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.9 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 167 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81.1 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 264 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 230 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 102 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61.1 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 130 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.1 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 499 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 89 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 1237.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.2 |
| Part 1: Placebo | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 1010 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 177 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.2 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 232 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 901 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 800.73 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 72.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 692 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 100 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 72.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 168 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.9 |
Secondary
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC
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.
Time frame: Day 2 to Day 18
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 600 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC | 0 Participants |
| Part 1: EDP-938 500 mg Then 300 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC | 0 Participants |
| Part 1: Placebo | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC | 0 Participants |
| Part 2: EDP-938 600 mg Then 300 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC | 0 Participants |
Secondary
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC
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.
Time frame: Day 2 to Day 18
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 600 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC | 0 Participants |
| Part 1: EDP-938 500 mg Then 300 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC | 0 Participants |
| Part 1: Placebo | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC | 0 Participants |
| Part 2: EDP-938 600 mg Then 300 mg | Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC | 0 Participants |
Secondary
Peak Total Symptom Score
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, with a potential range of 0 (best) to 30 (worst). 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
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Peak Total Symptom Score | 2.3 Scores on a scale | Geometric Coefficient of Variation 53.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Peak Total Symptom Score | 1.9 Scores on a scale | Geometric Coefficient of Variation 89.8 |
| Part 1: Placebo | Peak Total Symptom Score | 4.9 Scores on a scale | Geometric Coefficient of Variation 77.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Peak Total Symptom Score | 1.6 Scores on a scale | Geometric Coefficient of Variation 68.5 |
| Part 2: EDP-938 400 mg Then 200 mg | Peak Total Symptom Score | 1.8 Scores on a scale | Geometric Coefficient of Variation 55.6 |
| Part 2: Placebo | Peak Total Symptom Score | 4.2 Scores on a scale | Geometric Coefficient of Variation 85.8 |
p-value: <0.00195% CI: [-5.3, -2]ANCOVA
p-value: <0.00195% CI: [-5.5, -2.4]ANCOVA
p-value: =0.00295% CI: [-4.9, -1.2]ANCOVA
p-value: =0.00695% CI: [-4.9, -0.9]ANCOVA
Secondary
Peak Viral Load
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.
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Peak Viral Load | 4.3552 log10 copies/milliliter (mL) | Standard Deviation 1.56334 |
| Part 1: EDP-938 500 mg Then 300 mg | Peak Viral Load | 4.3111 log10 copies/milliliter (mL) | Standard Deviation 1.76974 |
| Part 1: Placebo | Peak Viral Load | 6.4727 log10 copies/milliliter (mL) | Standard Deviation 1.60659 |
| Part 2: EDP-938 600 mg Then 300 mg | Peak Viral Load | 3.9718 log10 copies/milliliter (mL) | Standard Deviation 1.78873 |
| Part 2: EDP-938 400 mg Then 200 mg | Peak Viral Load | 4.7727 log10 copies/milliliter (mL) | Standard Deviation 1.35014 |
| Part 2: Placebo | Peak Viral Load | 7.0973 log10 copies/milliliter (mL) | Standard Deviation 1.24388 |
p-value: <0.00195% CI: [-2.8491, -1.4093]ANCOVA
p-value: <0.00195% CI: [-2.7938, -1.4319]ANCOVA
p-value: <0.00195% CI: [-4.1915, -2.2467]ANCOVA
p-value: <0.00195% CI: [-3.8522, -1.714]ANCOVA
Secondary
Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 7; 12 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification. C12 is only reported for twice daily (BID) dosing groups relative to the last dose. Data were specifically collected for BID dosing groups at the specified times.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EDP-938 First Dose | 679.35 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.5 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 822 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.2 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024636 First Dose | 168 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 228 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024594 First Dose | 75.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.4 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 188 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.4 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024595 First Dose | 100 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 705 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 515 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EDP-938 First Dose | 565.60 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024594 First Dose | 68.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.8 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 525 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024595 First Dose | 99.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 75.4 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024636 First Dose | 149 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 133 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.7 |
| Part 2: EDP-938 600 mg Then 300 mg | Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 153 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.9 |
Secondary
Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 7; 24 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification. C24 is only reported for once daily (OD) dosing groups relative to last dose. Data were specifically collected for OD dosing groups at the specified times.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EDP-938 First Dose | 404 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.9 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 491 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.4 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024636 First Dose | 121 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.5 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 148 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.4 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024594 First Dose | 78.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.7 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 127 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.3 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024595 First Dose | 142 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.5 |
| Part 1: EDP-938 600 mg | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 461 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.6 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 287 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 93.8 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EDP-938 First Dose | 453 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.6 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024594 First Dose | 87.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 287 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024595 First Dose | 163 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79.4 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024636 First Dose | 136 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.5 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 74.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 72.4 |
| Part 1: Placebo | Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 88.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.8 |
Secondary
Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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 adverse events.
Time frame: Day 2 to Day 28
Population: Safety Analysis Set, defined as all participants who received challenge virus, whether they received study drug or not. One inoculated participant was not randomized to a specific treatment assignment and is not included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 600 mg | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 20 Participants |
| Part 1: EDP-938 500 mg Then 300 mg | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
| Part 1: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
| Part 2: EDP-938 600 mg Then 300 mg | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 8 Participants |
| Part 2: EDP-938 400 mg Then 200 mg | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 10 Participants |
| Part 2: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 11 Participants |
Secondary
Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EDP-938 | 14.5 Hours | Geometric Coefficient of Variation 25.4 |
| Part 1: EDP-938 600 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024636 | 14.5 Hours | Geometric Coefficient of Variation 21.5 |
| Part 1: EDP-938 600 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024594 | 17.8 Hours | Geometric Coefficient of Variation 18.2 |
| Part 1: EDP-938 600 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024595 | 28.5 Hours | Geometric Coefficient of Variation 38.2 |
| Part 1: EDP-938 500 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024636 | 13.4 Hours | Geometric Coefficient of Variation 21.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024594 | 16.2 Hours | Geometric Coefficient of Variation 18.5 |
| Part 1: EDP-938 500 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024595 | 25.5 Hours | Geometric Coefficient of Variation 25.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EDP-938 | 13.8 Hours | Geometric Coefficient of Variation 27.4 |
| Part 1: Placebo | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024594 | 17.5 Hours | Geometric Coefficient of Variation 25.1 |
| Part 1: Placebo | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024636 | 14.4 Hours | Geometric Coefficient of Variation 29.8 |
| Part 1: Placebo | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024595 | 22.7 Hours | Geometric Coefficient of Variation 15.6 |
| Part 1: Placebo | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EDP-938 | 14.5 Hours | Geometric Coefficient of Variation 31.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024595 | 23.0 Hours | Geometric Coefficient of Variation 19.4 |
| Part 2: EDP-938 600 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024636 | 13.5 Hours | Geometric Coefficient of Variation 21.2 |
| Part 2: EDP-938 600 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EDP-938 | 13.7 Hours | Geometric Coefficient of Variation 23.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites | EP-024594 | 15.4 Hours | Geometric Coefficient of Variation 17 |
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
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | 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 | EP-024594 | 0.04 1/hour | Geometric Coefficient of Variation 0.7 |
| Part 1: EDP-938 600 mg | 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 | EP-024636 | 0.05 1/hour | Geometric Coefficient of Variation 1.1 |
| Part 1: EDP-938 600 mg | 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 | EDP-938 | 0.05 1/hour | Geometric Coefficient of Variation 1.2 |
| Part 1: EDP-938 600 mg | 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 | EP-024595 | 0.03 1/hour | Geometric Coefficient of Variation 1.3 |
| Part 1: EDP-938 500 mg Then 300 mg | 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 | EP-024636 | 0.05 1/hour | Geometric Coefficient of Variation 1.2 |
| Part 1: EDP-938 500 mg Then 300 mg | 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 | EDP-938 | 0.05 1/hour | Geometric Coefficient of Variation 1.6 |
| Part 1: EDP-938 500 mg Then 300 mg | 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 | EP-024594 | 0.04 1/hour | Geometric Coefficient of Variation 0.8 |
| Part 1: EDP-938 500 mg Then 300 mg | 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 | EP-024595 | 0.03 1/hour | Geometric Coefficient of Variation 0.9 |
| Part 1: Placebo | 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 | EDP-938 | 0.05 1/hour | Geometric Coefficient of Variation 1.5 |
| Part 1: Placebo | 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 | EP-024595 | 0.03 1/hour | Geometric Coefficient of Variation 0.5 |
| Part 1: Placebo | 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 | EP-024594 | 0.04 1/hour | Geometric Coefficient of Variation 1 |
| Part 1: Placebo | 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 | EP-024636 | 0.05 1/hour | Geometric Coefficient of Variation 1.3 |
| Part 2: EDP-938 600 mg Then 300 mg | 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 | EP-024636 | 0.05 1/hour | Geometric Coefficient of Variation 1.1 |
| Part 2: EDP-938 600 mg Then 300 mg | 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 | EP-024595 | 0.03 1/hour | Geometric Coefficient of Variation 0.6 |
| Part 2: EDP-938 600 mg Then 300 mg | 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 | EDP-938 | 0.05 1/hour | Geometric Coefficient of Variation 1.2 |
| Part 2: EDP-938 600 mg Then 300 mg | 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 | EP-024594 | 0.05 1/hour | Geometric Coefficient of Variation 0.8 |
Secondary
Time to Cessation of Virus Detection
Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection. Participants were excluded from the analysis if it was concluded that the criteria for laboratory-confirmed RSV infection were not met.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: EDP-938 600 mg | Time to Cessation of Virus Detection | 3.5 Days |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Cessation of Virus Detection | 3.2 Days |
| Part 1: Placebo | Time to Cessation of Virus Detection | 8.5 Days |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Cessation of Virus Detection | 2.7 Days |
| Part 2: EDP-938 400 mg Then 200 mg | Time to Cessation of Virus Detection | 2.5 Days |
| Part 2: Placebo | Time to Cessation of Virus Detection | 8.5 Days |
p-value: <0.001Log Rank
p-value: <0.001Log Rank
p-value: =0.001Log Rank
p-value: <0.001Log Rank
Secondary
Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 4.56 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 4.52 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 5.91 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 5.00 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 10.07 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 8.07 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 23.72 Hours |
| Part 1: EDP-938 600 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 10.90 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 4.98 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 10.23 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 4.10 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 5.07 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 11.85 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 4.88 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 5.97 Hours |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 5.00 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 23.75 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 7.97 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 6.00 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 11.83 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 8.00 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 11.88 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 5.80 Hours |
| Part 1: Placebo | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 4.98 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 First Dose | 6.99 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024636 Last Dose | 4.04 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 Last Dose | 4.04 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EDP-938 First Dose | 6.07 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 First Dose | 10.14 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 Last Dose | 4.04 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024595 First Dose | 11.83 Hours |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites | EP-024594 Last Dose | 5.03 Hours |
Secondary
Time to Peak Total Symptom Score
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.
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Time to Peak Total Symptom Score | 1.18 Days | Geometric Coefficient of Variation 137.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Peak Total Symptom Score | 1.76 Days | Geometric Coefficient of Variation 110 |
| Part 1: Placebo | Time to Peak Total Symptom Score | 2.15 Days | Geometric Coefficient of Variation 71.4 |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Peak Total Symptom Score | 1.45 Days | Geometric Coefficient of Variation 131.9 |
| Part 2: EDP-938 400 mg Then 200 mg | Time to Peak Total Symptom Score | 1.09 Days | Geometric Coefficient of Variation 136.4 |
| Part 2: Placebo | Time to Peak Total Symptom Score | 1.94 Days | Geometric Coefficient of Variation 80.5 |
p-value: =0.19995% CI: [-2.09, 0.44]ANCOVA
p-value: =0.71495% CI: [-0.98, 1.43]ANCOVA
p-value: =0.84495% CI: [-2.15, 1.77]ANCOVA
p-value: =0.2195% CI: [-3.46, 0.79]ANCOVA
Secondary
Time to Peak Viral Load
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.
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Time to Peak Viral Load | 0.74 Days | Geometric Coefficient of Variation 75.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Peak Viral Load | 0.80 Days | Geometric Coefficient of Variation 130.2 |
| Part 1: Placebo | Time to Peak Viral Load | 2.59 Days | Geometric Coefficient of Variation 48.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Peak Viral Load | 0.88 Days | Geometric Coefficient of Variation 181.3 |
| Part 2: EDP-938 400 mg Then 200 mg | Time to Peak Viral Load | 0.79 Days | Geometric Coefficient of Variation 64 |
| Part 2: Placebo | Time to Peak Viral Load | 3.43 Days | Geometric Coefficient of Variation 33.7 |
p-value: <0.00195% CI: [-2.67, -1.35]ANCOVA
p-value: <0.00195% CI: [-2.4, -1.16]ANCOVA
p-value: =0.00995% CI: [-3.43, -0.54]ANCOVA
p-value: =0.00495% CI: [-4, -0.82]ANCOVA
Secondary
Time to Resolution From Peak Total Symptom Score
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.
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.~9 participants in Part 1 and 5 participants in Part 2 were excluded from the analysis due to having no symptoms in the interval first dose of study drug to Day 12.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Time to Resolution From Peak Total Symptom Score | 2.49 Days | Geometric Coefficient of Variation 70.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Resolution From Peak Total Symptom Score | 2.83 Days | Geometric Coefficient of Variation 77.5 |
| Part 1: Placebo | Time to Resolution From Peak Total Symptom Score | 3.30 Days | Geometric Coefficient of Variation 61.7 |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Resolution From Peak Total Symptom Score | 2.19 Days | Geometric Coefficient of Variation 70 |
| Part 2: EDP-938 400 mg Then 200 mg | Time to Resolution From Peak Total Symptom Score | 1.38 Days | Geometric Coefficient of Variation 116.5 |
| Part 2: Placebo | Time to Resolution From Peak Total Symptom Score | 5.17 Days | Geometric Coefficient of Variation 383 |
p-value: =0.14595% CI: [-2.37, 0.36]ANCOVA
p-value: =0.35295% CI: [-2.03, 0.73]ANCOVA
p-value: =0.00295% CI: [-4.55, -1.15]ANCOVA
p-value: <0.00195% CI: [-5.19, -1.61]ANCOVA
Secondary
Time to Resolution From Peak Viral Load
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).
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection. Participants were excluded from the analysis if it was concluded that the criteria for laboratory-confirmed RSV infection were not met.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Time to Resolution From Peak Viral Load | 2.03 Days | Geometric Coefficient of Variation 72.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Time to Resolution From Peak Viral Load | 2.02 Days | Geometric Coefficient of Variation 79.7 |
| Part 1: Placebo | Time to Resolution From Peak Viral Load | 4.03 Days | Geometric Coefficient of Variation 47.5 |
| Part 2: EDP-938 600 mg Then 300 mg | Time to Resolution From Peak Viral Load | 1.67 Days | Geometric Coefficient of Variation 77.1 |
| Part 2: EDP-938 400 mg Then 200 mg | Time to Resolution From Peak Viral Load | 1.63 Days | Geometric Coefficient of Variation 43.7 |
| Part 2: Placebo | Time to Resolution From Peak Viral Load | 3.58 Days | Geometric Coefficient of Variation 45.6 |
p-value: <0.00195% CI: [-3.04, -1.17]ANCOVA
p-value: <0.00195% CI: [-2.89, -1.11]ANCOVA
p-value: <0.00195% CI: [-3.06, -0.89]ANCOVA
p-value: <0.00195% CI: [-3.64, -1.29]ANCOVA
Secondary
Total Symptom Score
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. Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise (Tiredness) * Cough * Shortness of breath * Headache * Muscle/ joint ache/ stiffness
Time frame: Day 2 to Day 9
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection. For cases of 0 participants analyzed, data were not collected from any participants for that time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 4 Assessment 2 | 0.3 Scores on a scale | Geometric Coefficient of Variation 186.5 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 4 Assessment 3 | 0.3 Scores on a scale | Geometric Coefficient of Variation 263 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 5 Assessment 2 | 0.3 Scores on a scale | Geometric Coefficient of Variation 191.3 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 4 Assessment 1 | 0.3 Scores on a scale | Geometric Coefficient of Variation 177.1 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 9 Assessment 2 | 0.0 Scores on a scale | — |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 5 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 228.2 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 6 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 300.9 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 8 Assessment 3 | 0.0 Scores on a scale | — |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 8 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 374.2 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 8 Assessment 1 | 0.1 Scores on a scale | Geometric Coefficient of Variation 291 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 2 Assessment 1 | 0.9 Scores on a scale | Geometric Coefficient of Variation 97.5 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 7 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 291 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 2 Assessment 2 | 0.8 Scores on a scale | Geometric Coefficient of Variation 94 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 9 Assessment 1 | 0.0 Scores on a scale | — |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 7 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 196.2 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 7 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 225.1 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 2 Assessment 3 | 0.5 Scores on a scale | Geometric Coefficient of Variation 117 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 6 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 280.9 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 3 Assessment 1 | 0.4 Scores on a scale | Geometric Coefficient of Variation 137.3 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 6 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 288.7 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 3 Assessment 2 | 0.4 Scores on a scale | Geometric Coefficient of Variation 144.3 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 5 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 364.8 |
| Part 1: EDP-938 600 mg | Total Symptom Score | Relative Day 3 Assessment 3 | 0.3 Scores on a scale | Geometric Coefficient of Variation 190.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 3 | 0.4 Scores on a scale | Geometric Coefficient of Variation 162 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 162 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 2 | 0.4 Scores on a scale | Geometric Coefficient of Variation 177.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 2 | 0.4 Scores on a scale | Geometric Coefficient of Variation 186.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 1 | 0.5 Scores on a scale | Geometric Coefficient of Variation 158.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 2 | 0.6 Scores on a scale | Geometric Coefficient of Variation 175.2 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 1 | 0.5 Scores on a scale | Geometric Coefficient of Variation 154.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 1 | 0.7 Scores on a scale | Geometric Coefficient of Variation 148.5 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 205.3 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 3 | 0.4 Scores on a scale | Geometric Coefficient of Variation 163.5 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 3 | 0.6 Scores on a scale | Geometric Coefficient of Variation 167.7 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 9 Assessment 1 | 0.0 Scores on a scale | — |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 2 | 0.7 Scores on a scale | Geometric Coefficient of Variation 160.3 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 9 Assessment 2 | 0.0 Scores on a scale | — |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 3 | 0.4 Scores on a scale | Geometric Coefficient of Variation 149.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 1 | 0.4 Scores on a scale | Geometric Coefficient of Variation 186.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 244.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 3 | 0.6 Scores on a scale | Geometric Coefficient of Variation 184.4 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 199.9 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 2 | 0.6 Scores on a scale | Geometric Coefficient of Variation 163.1 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 185.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 3 | 0.3 Scores on a scale | Geometric Coefficient of Variation 184.6 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 1 | 0.8 Scores on a scale | Geometric Coefficient of Variation 155.4 |
| Part 1: Placebo | Total Symptom Score | Relative Day 9 Assessment 2 | 0.5 Scores on a scale | Geometric Coefficient of Variation 91.3 |
| Part 1: Placebo | Total Symptom Score | Relative Day 3 Assessment 2 | 2.7 Scores on a scale | Geometric Coefficient of Variation 90.5 |
| Part 1: Placebo | Total Symptom Score | Relative Day 4 Assessment 2 | 1.8 Scores on a scale | Geometric Coefficient of Variation 115.3 |
| Part 1: Placebo | Total Symptom Score | Relative Day 5 Assessment 2 | 1.4 Scores on a scale | Geometric Coefficient of Variation 109.2 |
| Part 1: Placebo | Total Symptom Score | Relative Day 5 Assessment 3 | 1.3 Scores on a scale | Geometric Coefficient of Variation 115.9 |
| Part 1: Placebo | Total Symptom Score | Relative Day 6 Assessment 1 | 1.2 Scores on a scale | Geometric Coefficient of Variation 106 |
| Part 1: Placebo | Total Symptom Score | Relative Day 2 Assessment 2 | 2.4 Scores on a scale | Geometric Coefficient of Variation 110.3 |
| Part 1: Placebo | Total Symptom Score | Relative Day 2 Assessment 3 | 2.7 Scores on a scale | Geometric Coefficient of Variation 94.9 |
| Part 1: Placebo | Total Symptom Score | Relative Day 3 Assessment 1 | 2.6 Scores on a scale | Geometric Coefficient of Variation 99.1 |
| Part 1: Placebo | Total Symptom Score | Relative Day 3 Assessment 3 | 2.5 Scores on a scale | Geometric Coefficient of Variation 103.7 |
| Part 1: Placebo | Total Symptom Score | Relative Day 4 Assessment 1 | 2.3 Scores on a scale | Geometric Coefficient of Variation 103.8 |
| Part 1: Placebo | Total Symptom Score | Relative Day 4 Assessment 3 | 1.8 Scores on a scale | Geometric Coefficient of Variation 103.1 |
| Part 1: Placebo | Total Symptom Score | Relative Day 5 Assessment 1 | 1.6 Scores on a scale | Geometric Coefficient of Variation 108.3 |
| Part 1: Placebo | Total Symptom Score | Relative Day 6 Assessment 2 | 1.0 Scores on a scale | Geometric Coefficient of Variation 112.8 |
| Part 1: Placebo | Total Symptom Score | Relative Day 6 Assessment 3 | 1.0 Scores on a scale | Geometric Coefficient of Variation 100.5 |
| Part 1: Placebo | Total Symptom Score | Relative Day 7 Assessment 1 | 0.7 Scores on a scale | Geometric Coefficient of Variation 124.9 |
| Part 1: Placebo | Total Symptom Score | Relative Day 7 Assessment 2 | 0.7 Scores on a scale | Geometric Coefficient of Variation 115.7 |
| Part 1: Placebo | Total Symptom Score | Relative Day 7 Assessment 3 | 0.9 Scores on a scale | Geometric Coefficient of Variation 89.9 |
| Part 1: Placebo | Total Symptom Score | Relative Day 8 Assessment 1 | 0.9 Scores on a scale | Geometric Coefficient of Variation 94.9 |
| Part 1: Placebo | Total Symptom Score | Relative Day 8 Assessment 2 | 0.9 Scores on a scale | Geometric Coefficient of Variation 99.4 |
| Part 1: Placebo | Total Symptom Score | Relative Day 8 Assessment 3 | 0.6 Scores on a scale | Geometric Coefficient of Variation 129.1 |
| Part 1: Placebo | Total Symptom Score | Relative Day 9 Assessment 1 | 0.4 Scores on a scale | Geometric Coefficient of Variation 140.5 |
| Part 1: Placebo | Total Symptom Score | Relative Day 2 Assessment 1 | 1.9 Scores on a scale | Geometric Coefficient of Variation 117 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 387.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 1 | 0.1 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 1 | 0.4 Scores on a scale | Geometric Coefficient of Variation 166.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 1 | 0.1 Scores on a scale | Geometric Coefficient of Variation 387.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 264.6 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 8 Assessment 3 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 9 Assessment 1 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 387.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 280.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 3 | 0.3 Scores on a scale | Geometric Coefficient of Variation 196.2 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 244.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 387.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 4 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 343.9 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 280.3 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 2 | 0.4 Scores on a scale | Geometric Coefficient of Variation 185.2 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 332.6 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 3 Assessment 2 | 0.3 Scores on a scale | Geometric Coefficient of Variation 207 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 346.4 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 6 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 314 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 2 Assessment 1 | 0.5 Scores on a scale | Geometric Coefficient of Variation 140.8 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 7 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 9 Assessment 2 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 600 mg Then 300 mg | Total Symptom Score | Relative Day 5 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 314 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 8 Assessment 1 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 7 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 300 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 2 Assessment 1 | 0.3 Scores on a scale | Geometric Coefficient of Variation 222.5 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 6 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 210.8 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 5 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 254.2 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 3 Assessment 3 | 0.3 Scores on a scale | Geometric Coefficient of Variation 276.4 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 8 Assessment 2 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 3 Assessment 2 | 0.3 Scores on a scale | Geometric Coefficient of Variation 237.1 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 2 Assessment 2 | 0.5 Scores on a scale | Geometric Coefficient of Variation 179.8 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 6 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 237.1 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 4 Assessment 2 | 0.1 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 2 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 5 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 6 Assessment 2 | 0.3 Scores on a scale | Geometric Coefficient of Variation 185.4 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 7 Assessment 1 | 0.1 Scores on a scale | Geometric Coefficient of Variation 316.2 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 4 Assessment 3 | 0.1 Scores on a scale | Geometric Coefficient of Variation 331.7 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 7 Assessment 3 | 0.0 Scores on a scale | — |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 4 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 254.2 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 5 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 254.2 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Symptom Score | Relative Day 3 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 254.2 |
| Part 2: Placebo | Total Symptom Score | Relative Day 4 Assessment 1 | 1.9 Scores on a scale | Geometric Coefficient of Variation 92.6 |
| Part 2: Placebo | Total Symptom Score | Relative Day 5 Assessment 1 | 1.6 Scores on a scale | Geometric Coefficient of Variation 87.9 |
| Part 2: Placebo | Total Symptom Score | Relative Day 5 Assessment 2 | 1.4 Scores on a scale | Geometric Coefficient of Variation 112.8 |
| Part 2: Placebo | Total Symptom Score | Relative Day 3 Assessment 2 | 2.3 Scores on a scale | Geometric Coefficient of Variation 101 |
| Part 2: Placebo | Total Symptom Score | Relative Day 5 Assessment 3 | 1.4 Scores on a scale | Geometric Coefficient of Variation 89.6 |
| Part 2: Placebo | Total Symptom Score | Relative Day 6 Assessment 1 | 1.5 Scores on a scale | Geometric Coefficient of Variation 83.3 |
| Part 2: Placebo | Total Symptom Score | Relative Day 2 Assessment 3 | 2.6 Scores on a scale | Geometric Coefficient of Variation 94.3 |
| Part 2: Placebo | Total Symptom Score | Relative Day 8 Assessment 3 | 0.2 Scores on a scale | Geometric Coefficient of Variation 200 |
| Part 2: Placebo | Total Symptom Score | Relative Day 6 Assessment 3 | 1.1 Scores on a scale | Geometric Coefficient of Variation 116.5 |
| Part 2: Placebo | Total Symptom Score | Relative Day 2 Assessment 2 | 2.9 Scores on a scale | Geometric Coefficient of Variation 82.5 |
| Part 2: Placebo | Total Symptom Score | Relative Day 7 Assessment 1 | 0.8 Scores on a scale | Geometric Coefficient of Variation 126.1 |
| Part 2: Placebo | Total Symptom Score | Relative Day 2 Assessment 1 | 3.0 Scores on a scale | Geometric Coefficient of Variation 66.6 |
| Part 2: Placebo | Total Symptom Score | Relative Day 3 Assessment 1 | 2.2 Scores on a scale | Geometric Coefficient of Variation 103 |
| Part 2: Placebo | Total Symptom Score | Relative Day 9 Assessment 2 | 0.4 Scores on a scale | Geometric Coefficient of Variation 141.4 |
| Part 2: Placebo | Total Symptom Score | Relative Day 7 Assessment 3 | 0.7 Scores on a scale | Geometric Coefficient of Variation 179.2 |
| Part 2: Placebo | Total Symptom Score | Relative Day 8 Assessment 1 | 0.5 Scores on a scale | Geometric Coefficient of Variation 153.7 |
| Part 2: Placebo | Total Symptom Score | Relative Day 7 Assessment 2 | 0.9 Scores on a scale | Geometric Coefficient of Variation 153.5 |
| Part 2: Placebo | Total Symptom Score | Relative Day 9 Assessment 1 | 0.2 Scores on a scale | Geometric Coefficient of Variation 200 |
| Part 2: Placebo | Total Symptom Score | Relative Day 8 Assessment 2 | 0.2 Scores on a scale | Geometric Coefficient of Variation 170.8 |
| Part 2: Placebo | Total Symptom Score | Relative Day 6 Assessment 2 | 1.2 Scores on a scale | Geometric Coefficient of Variation 102.4 |
| Part 2: Placebo | Total Symptom Score | Relative Day 4 Assessment 2 | 1.7 Scores on a scale | Geometric Coefficient of Variation 85 |
| Part 2: Placebo | Total Symptom Score | Relative Day 4 Assessment 3 | 1.8 Scores on a scale | Geometric Coefficient of Variation 88.3 |
| Part 2: Placebo | Total Symptom Score | Relative Day 3 Assessment 3 | 2.2 Scores on a scale | Geometric Coefficient of Variation 95.3 |
Secondary
Total Weight of Nasal Mucus Produced
Measured via weighed paper tissues and reported as a mean total across all study days.
Time frame: Day 2 to Day 12
Population: Intent to Treat Infected (ITT-I) Analysis Set, defined as all randomised participants who received challenge virus and at least one dose of investigational medicinal product (IMP), and who met the criterion for laboratory confirmed respiratory syncytial virus (RSV) infection as per the definition of laboratory confirmed infection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Total Weight of Nasal Mucus Produced | 12.965 Grams | Standard Deviation 13.0314 |
| Part 1: EDP-938 500 mg Then 300 mg | Total Weight of Nasal Mucus Produced | 7.428 Grams | Standard Deviation 11.1324 |
| Part 1: Placebo | Total Weight of Nasal Mucus Produced | 33.416 Grams | Standard Deviation 37.8072 |
| Part 2: EDP-938 600 mg Then 300 mg | Total Weight of Nasal Mucus Produced | 2.983 Grams | Standard Deviation 4.4226 |
| Part 2: EDP-938 400 mg Then 200 mg | Total Weight of Nasal Mucus Produced | 4.716 Grams | Standard Deviation 6.0015 |
| Part 2: Placebo | Total Weight of Nasal Mucus Produced | 22.391 Grams | Standard Deviation 20.6005 |
p-value: <0.00195% CI: [-36.554, -11.607]ANCOVA
p-value: <0.00195% CI: [-37.695, -14.213]ANCOVA
p-value: <0.00195% CI: [-27.176, -9.083]ANCOVA
p-value: <0.00195% CI: [-29.106, -9.552]ANCOVA
Secondary
Volume of Distribution at Steady State (Vss/F) of EDP-938
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Population: Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. Participants were excluded from the analysis if plasma concentrations were below the limit of quantification.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 600 mg | Volume of Distribution at Steady State (Vss/F) of EDP-938 | 560 litre(s) | Geometric Coefficient of Variation 42.8 |
| Part 1: EDP-938 500 mg Then 300 mg | Volume of Distribution at Steady State (Vss/F) of EDP-938 | 476 litre(s) | Geometric Coefficient of Variation 23.1 |
| Part 1: Placebo | Volume of Distribution at Steady State (Vss/F) of EDP-938 | 442 litre(s) | Geometric Coefficient of Variation 24.1 |
| Part 2: EDP-938 600 mg Then 300 mg | Volume of Distribution at Steady State (Vss/F) of EDP-938 | 491 litre(s) | Geometric Coefficient of Variation 28.8 |