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| Name | Class |
|---|---|
| hVIVO Services Limited | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EDP-938 Arm A | Experimental | Subjects will take EDP-938 Dose 1 oral suspension for 5 days |
|
| EDP-938 Arm B | Experimental | Subjects will take EDP-938 Dose 2 oral suspension for 5 days |
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| Placebo Arm C | Placebo Comparator | Subjects will take matching placebo oral suspension for 5 days |
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| EDP-938 Arm D | Experimental | Subjects will take EDP-938 Dose 3 oral suspension for 5 days |
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| EDP-938 Arm E | Experimental | Subjects will take EDP-938 Dose 4 oral suspension for 5 days |
|
| Placebo Arm F | Placebo Comparator | Subjects will take matching placebo oral suspension for 5 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EDP-938 Dose 1 | Drug | Oral suspension for 5 days |
| |
| EDP-938 Dose 2 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Twice daily on Day 2 through Day 11 and once on Day 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Enanta Pharmaceuticals, Inc | Enanta Pharmaceuticals, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| hVIVO Services Limited (hVIVO) | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39441691 | Derived | Levene RE, DeVincenzo J, Conery AL, Ahmad A, Or YS, Rhodin MHJ. EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus. J Infect Dis. 2025 Feb 20;231(2):e290-e298. doi: 10.1093/infdis/jiae471. | |
| 35172056 | Derived | Ahmad A, Eze K, Noulin N, Horvathova V, Murray B, Baillet M, Grey L, Mori J, Adda N. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med. 2022 Feb 17;386(7):655-666. doi: 10.1056/NEJMoa2108903. |
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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.
A total of 179 participants enrolled in the trial at one site in the United Kingdom from October 2018 to October 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | Part 1: Placebo | Participants were administered a placebo BID (every 12 hours) for a total of 10 doses over 5 days. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | Part 2: Placebo | Participants were administered a placebo BID for 5 days, with dosing at 12 hour intervals. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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In Part 1, one participant in the Safety Analysis Set did not receive study treatment and is not included in this baseline analysis population.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Part 1: EDP-938 500 mg Then 300 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*log10 copies/milliliter (mL) | Twice daily on Day 2 through Day 11 and once on Day 12 |
|
All cause mortality was monitored from enrollment until end of study (Day 28) for the safety analysis population which included all participants who received challenge virus, regardless of whether they received study drug or not. Treatment-emergent serious and other adverse events (AEs) were monitored from Day 2 to Day 28 and only included participants in the safety analysis population who received study drug.
An adverse event (AE) was defined as any untoward medical occurrence in participants (any unfavourable and unintended sign [including an abnormal laboratory finding], symptom, or disease temporally associated with the investigational medicinal product [IMP], whether or not considered related to IMP, or for Human Viral Challenge studies, the Challenge Virus). AEs were recorded in the source documents as they are reported, whether volunteered by a participant or in response to questioning.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Guy De La Rosa, MD, Senior Medical Director, Infectious Diseases | Enanta Pharmaceuticals, Inc. | +1 857 760 0548 | gdelarosa@enanta.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 7, 2019 | Feb 21, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 1, 2019 | Feb 21, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D018357 | Respiratory Syncytial Virus Infections |
| ID | Term |
|---|---|
| D018186 | Pneumovirus Infections |
| D018184 | Paramyxoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
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|
| Drug |
Oral suspension for 5 days |
|
| Placebo | Drug | Oral suspension for 5 days |
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| EDP-938 Dose 3 | Drug | Oral suspension for 5 days |
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| EDP-938 Dose 4 | Drug | Oral suspension for 5 days |
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| Placebo | Drug | Oral suspension for 5 days |
|
| Three times daily on Day 0 to Day 11, once on Day 12 |
| 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:
| Day 2 to Day 12 |
| 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).
| Day 2 to Day 9 |
| 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. | Day 2 to Day 12 |
| 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. | Day 2 to Day 12 |
| Total Weight of Nasal Mucus Produced | Measured via weighed paper tissues and reported as a mean total across all study days. | Day 2 to Day 12 |
| 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. | Day 2 to Day 12 |
| 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. | Day 2 to Day 12 |
| 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). | Day 2 to Day 12 |
| 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). | Day 2 to Day 12 |
| 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. | Day 2 to Day 28 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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 | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. | 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 |
| 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 | The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595. | Day 2 and Day 7; 12 hours post-dose |
| 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. | Day 2 and Day 7; 24 hours post-dose |
| 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. | 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 |
| 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. | 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 |
| 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. | Day 2 to Day 18 |
| 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. | Day 2 to Day 18 |
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.
| BG002 | Part 1: Placebo | Participants were administered a placebo BID (every 12 hours) for a total of 10 doses over 5 days. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Part 2: Placebo | Participants were administered a placebo BID for 5 days, with dosing at 12 hour intervals. |
| BG006 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| OG001 | 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. |
| OG002 | Part 1: Placebo | Participants were administered a placebo BID (every 12 hours) for a total of 10 doses over 5 days. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | Part 2: Placebo | Participants were administered a placebo BID for 5 days, with dosing at 12 hour intervals. |
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| 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:
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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*score | Three times daily on Day 0 to Day 11, once on Day 12 |
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| 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:
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Scores on a scale | Day 2 to Day 12 |
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| 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).
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Scores on a scale | Day 2 to Day 9 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Days | Day 2 to Day 12 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Days | Day 2 to Day 12 |
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| Secondary | Total Weight of Nasal Mucus Produced | Measured via weighed paper tissues and reported as a mean total across all study days. | 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. | Posted | Mean | Standard Deviation | Grams | Day 2 to Day 12 |
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| 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. | 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. | Posted | Mean | Standard Deviation | log10 copies/milliliter (mL) | Day 2 to Day 12 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Days | Day 2 to Day 12 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Days | Day 2 to Day 12 |
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| 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). | 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. | Posted | Median | Inter-Quartile Range | Days | Day 2 to Day 12 |
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| 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. | 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. | Posted | Count of Participants | Participants | Day 2 to Day 28 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 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 |
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| 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. | 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. | Posted | Median | Full Range | Hours | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| Secondary | Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litres per hour | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hour | 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 |
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| Secondary | Volume of Distribution at Steady State (Vss/F) of EDP-938 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litre(s) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Day 2 and Day 7; 12 hours post-dose |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Day 2 and Day 7; 24 hours post-dose |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. | Posted | Count of Participants | Participants | Day 2 to Day 18 |
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| 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. | Pharmacokinetic (PK) Analysis Set, defined as all Intent to Treat (ITT) participants with at least one post-dose PK result. | Posted | Count of Participants | Participants | Day 2 to Day 18 |
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|
|
| 0 |
| 39 |
| 0 |
| 38 |
| 20 |
| 38 |
| EG001 | 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. | 0 | 38 | 0 | 38 | 21 | 38 |
| EG002 | Part 1: Placebo | Participants were administered a placebo BID (every 12 hours) for a total of 10 doses over 5 days. | 0 | 38 | 0 | 38 | 21 | 38 |
| EG003 | 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. | 0 | 21 | 0 | 21 | 8 | 21 |
| EG004 | 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. | 0 | 21 | 0 | 21 | 10 | 21 |
| EG005 | Part 2: Placebo | Participants were administered a placebo BID for 5 days, with dosing at 12 hour intervals. | 0 | 21 | 0 | 21 | 11 | 21 |
| Hypoacusis | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
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| Blepharospasm | Eye disorders | MedDRA 21.1 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 21.1 | Systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal tenderness | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site related reaction | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Thirst | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Vessel puncture site paraesthesia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA 21.1 | Systematic Assessment |
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| Angular cheilitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Herpes simplex | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Viral tonsillitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Forced expiratory volume decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| FEV1/FVC ratio decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Forced vital capacity decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Skin mass | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
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| Micturition urgency | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
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First publication of Sponsor Data shall be made by Sponsor with input from principal investigator (PIs). If no publication within 24 months after study completion, PI may publish Sponsor Data with sponsor's prior written consent. Prior to submitting or presenting data, Sponsor has at least 60 days to to review and comment.
| D014777 | Virus Diseases |
| D007239 | Infections |
| LS Mean Difference |
| -326.64 |
| 2-Sided |
| 95 |
| -469.68 |
| -183.6 |
| Superiority |
| ANCOVA | = 0.001 | LS Mean Difference | -313.98 | 2-Sided | 95 | -494.27 | -133.69 | Superiority |
| ANCOVA | = 0.003 | LS Mean Difference | -312.73 | 2-Sided | 95 | -508.05 | -117.4 | Superiority |
| LS Mean Difference |
| -3.9 |
| 2-Sided |
| 95 |
| -5.5 |
| -2.4 |
| Superiority |
| ANCOVA | = 0.002 | LS Mean Difference | -3 | 2-Sided | 95 | -4.9 | -1.2 | Superiority |
| ANCOVA | = 0.006 | LS Mean Difference | -2.9 | 2-Sided | 95 | -4.9 | -0.9 | Superiority |
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| Relative Day 2 Assessment 2 |
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| Relative Day 2 Assessment 3 |
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| Relative Day 3 Assessment 1 |
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| Relative Day 3 Assessment 2 |
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| Relative Day 3 Assessment 3 |
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| Relative Day 4 Assessment 1 |
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| Relative Day 4 Assessment 2 |
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| Relative Day 4 Assessment 3 |
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| Relative Day 5 Assessment 1 |
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| Relative Day 5 Assessment 2 |
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| Relative Day 5 Assessment 3 |
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| Relative Day 6 Assessment 1 |
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| Relative Day 6 Assessment 2 |
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| Relative Day 6 Assessment 3 |
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| Relative Day 7 Assessment 1 |
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| Relative Day 7 Assessment 2 |
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| Relative Day 7 Assessment 3 |
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| Relative Day 8 Assessment 1 |
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| Relative Day 8 Assessment 2 |
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| Relative Day 8 Assessment 3 |
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| Relative Day 9 Assessment 1 |
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| Relative Day 9 Assessment 2 |
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|
| LS Mean Difference |
| 0.22 |
| 2-Sided |
| 95 |
| -0.98 |
| 1.43 |
| Superiority |
| ANCOVA | = 0.844 | LS Mean Difference | -0.19 | 2-Sided | 95 | -2.15 | 1.77 | Superiority |
| ANCOVA | = 0.21 | LS Mean Difference | -1.34 | 2-Sided | 95 | -3.46 | 0.79 | Superiority |
| LS Mean Difference |
| -0.65 |
| 2-Sided |
| 95 |
| -2.03 |
| 0.73 |
| Superiority |
| ANCOVA | = 0.002 | LS Mean Difference | -2.85 | 2-Sided | 95 | -4.55 | -1.15 | Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -3.4 | 2-Sided | 95 | -5.19 | -1.61 | Superiority |
| LS Mean Difference |
| -25.954 |
| 2-Sided |
| 95 |
| -37.695 |
| -14.213 |
| Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -18.13 | 2-Sided | 95 | -27.176 | -9.083 | Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -19.329 | 2-Sided | 95 | -29.106 | -9.552 | Superiority |
| LS Mean Difference |
| -2.1129 |
| 2-Sided |
| 95 |
| -2.7938 |
| -1.4319 |
| Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -3.2191 | 2-Sided | 95 | -4.1915 | -2.2467 | Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -2.7831 | 2-Sided | 95 | -3.8522 | -1.714 | Superiority |
| LS Mean Difference |
| -1.78 |
| 2-Sided |
| 95 |
| -2.4 |
| -1.16 |
| Superiority |
| ANCOVA | = 0.009 | LS Mean Difference | -1.98 | 2-Sided | 95 | -3.43 | -0.54 | Superiority |
| ANCOVA | = 0.004 | LS Mean Difference | -2.41 | 2-Sided | 95 | -4 | -0.82 | Superiority |
| LS Mean Difference |
| -2 |
| 2-Sided |
| 95 |
| -2.89 |
| -1.11 |
| Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -1.97 | 2-Sided | 95 | -3.06 | -0.89 | Superiority |
| ANCOVA | < 0.001 | LS Mean Difference | -2.46 | 2-Sided | 95 | -3.64 | -1.29 | Superiority |
| Superiority |
| Log Rank | = 0.001 | Superiority |
| Log Rank | < 0.001 | Superiority |
| EDP-938 Last Dose |
|
| EP-024636 First Dose |
|
| EP-024636 Last Dose |
|
| EP-024594 First Dose |
|
| EP-024594 Last Dose |
|
| EP-024595 First Dose |
|
| EP-024595 Last Dose |
|
| EDP-938 Last Dose |
|
| EP-024636 First Dose |
|
| EP-024636 Last Dose |
|
| EP-024594 First Dose |
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| EP-024594 Last Dose |
|
| EP-024595 First Dose |
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| EP-024595 Last Dose |
|
| EP-024636 |
|
| EP-024594 |
|
| EP-024595 |
|
| EP-024636 |
|
| EP-024594 |
|
| EP-024595 |
|
| EP-024636 First Dose |
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| EP-024636 Last Dose |
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| EP-024594 First Dose |
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| EP-024594 Last Dose |
|
| EP-024595 First Dose |
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| EP-024595 Last Dose |
|
| EP-024636 First Dose |
|
| EP-024636 Last Dose |
|
| EP-024594 First Dose |
|
| EP-024594 Last Dose |
|
| EP-024595 First Dose |
|
| EP-024595 Last Dose |
|
| EDP-938 Last Dose |
|
| EP-024636 First Dose |
|
| EP-024636 Last Dose |
|
| EP-024594 First Dose |
|
| EP-024594 Last Dose |
|
| EP-024595 First Dose |
|
| EP-024595 Last Dose |
|
| EP-024636 |
|
| EP-024594 |
|
| EP-024595 |
|