A Phase 2a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-4482 in Healthy Participants Inoculated With Experimental Influenza Virus
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 161
- Locations
- 1
- Primary Endpoint
- Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) From Day 1 PM Through Day 8 AM
Study Overview
Brief Summary
This is a phase 2a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of molnupiravir (MK-4482) in healthy participants inoculated with experimental influenza virus. The primary hypotheses are that MK-4482 initiated 12 hours following intranasal inoculation of the influenza challenge virus reduces the peak viral load compared to placebo and that MK-4482 initiated 2 days following intranasal inoculation of the influenza challenge virus reduces the viral load area under the curve (AUC) compared to placebo.
Detailed Description
This study has two parts. Part 1 is an open-label validation study, with a cohort of 20 untreated participants undergoing nasal inoculation with the A/France/759/21 [H1N1] strain on Day 0 to confirm viral infectivity and disease. Part 2 will be a randomized, double-blind placebo- and active-comparator-controlled study where participants will be inoculated on Day 0 with either the A/France/759/21 [H1N1] virus used in Part 1 or an alternative influenza virus. Part 2 will evaluate the antiviral efficacy, pharmacokinetics, and safety of MK-4482 in participants inoculated with the challenge virus.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Is in good health based on medical history, physical examination, vital sign measurements, spirometry, and electrocardiograms performed before inoculation.
- •Has a total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m^2 and ≤35 kg/m^
- •For males: abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent OR uses contraception unless confirmed to be azoospermic.
- •For participants assigned female sex at birth: is not pregnant or breastfeeding, AND is either not a person of childbearing potential (POCBP) or is a POCBP AND uses a contraceptive method that is highly effective (low user dependency method, OR a user dependent hormonal method in combination with barrier method), or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle, has a negative highly sensitive pregnancy test, abstains from breastfeeding, and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease risk of early undetected pregnancy.
Exclusion Criteria
- •Has a history of, or has currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to admission to quarantine.
- •Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases.
- •Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy visit, or expected during the conduct of the study, or has a history of clinically significant psychiatric disorder of the last 5 years.
- •Has a history of cancer.
- •Has a history of rhinitis which is clinically active, or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days prior to admission to quarantine.
- •Has a history of atopic dermatitis/eczema which is clinically severe and/or requiring moderate to large amounts of daily dermal corticosteroids.
- •Has a diagnosis of cluster headache/migraine or is receiving prophylaxis against migraine.
- •Has a lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. Significant intolerance to any food or drug in the last 12 months.
- •Has had major surgery and/or donated or lost 1 unit of blood within 3 months prior to the prestudy visit.
- •Uses or anticipates the use of concomitant medications, including vitamins or herbal and dietary supplements from approximately 2 weeks prior to the planned date of viral challenge until the poststudy visit.
- •Has evidence of receipt of vaccine within the 4 weeks prior to the planned date of viral challenge.
- •Intends to receive any vaccine(s) before the last day of follow-up.
- •Has received any investigational drug within 3 months prior to the planned date of viral challenge.
- •Has received 3 or more investigational drugs within the previous 12 months prior to the planned date of viral challenge.
- •Has had prior inoculation with a virus from the same virus subtype as the challenge virus.
- •Has had prior inoculation with a virus from the same virus-family as the challenge virus in the last 12 months.
- •Has had prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
- •Has smoked ≥10 pack-years at any time.
- •Has a recent history or presence of alcohol addiction, or excessive use of alcohol.
- •Consumes excessive amounts, defined as more than 6 servings of caffeinated beverages or xanthine-containing products.
- •Has any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and, in particular, any of the nasal assessments or viral challenge.
- •Has any clinically significant history of epistaxis.
- •Has had any nasal or sinus surgery within 3 months.
- •Is a regular user of cannabis or any illicit drugs, or has a history of drug abuse within approximately 1 year.
Arms & Interventions
Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2)
Molnupiravir 800 mg every 12 hours Day 0 PM through Day 5 AM, placebo molnupiravir every 12 hours Day 5 PM through Day 6 PM
Intervention: Molnupiravir (Drug)
Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2)
Molnupiravir 800 mg every 12 hours Day 0 PM through Day 5 AM, placebo molnupiravir every 12 hours Day 5 PM through Day 6 PM
Intervention: Placebo molnupiravir (Drug)
Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2)
Molnupiravir 800 mg every 12 hours Day 0 PM through Day 5 AM, placebo molnupiravir every 12 hours Day 5 PM through Day 6 PM
Intervention: Influenza A Virus (Biological)
Panel B: Molnupiravir Treatment (Part 2)
Placebo molnupiravir every 12 hours Day 0 PM through Day 1 PM, molnupiravir 800 mg every 12 hours Day 2 AM through Day 6 PM
Intervention: Molnupiravir (Drug)
Panel B: Molnupiravir Treatment (Part 2)
Placebo molnupiravir every 12 hours Day 0 PM through Day 1 PM, molnupiravir 800 mg every 12 hours Day 2 AM through Day 6 PM
Intervention: Placebo molnupiravir (Drug)
Panel B: Molnupiravir Treatment (Part 2)
Placebo molnupiravir every 12 hours Day 0 PM through Day 1 PM, molnupiravir 800 mg every 12 hours Day 2 AM through Day 6 PM
Intervention: Influenza A Virus (Biological)
Panel C: Oseltamivir Treatment (Part 2)
Placebo oseltamivir Day 0 PM through Day 1 PM, oseltamivir 75 mg plus placebo so the total number of capsules is always 4 per dose every 12 hours Day 2 AM through Day 6 PM
Intervention: Placebo oseltamivir (Drug)
Panel C: Oseltamivir Treatment (Part 2)
Placebo oseltamivir Day 0 PM through Day 1 PM, oseltamivir 75 mg plus placebo so the total number of capsules is always 4 per dose every 12 hours Day 2 AM through Day 6 PM
Intervention: Oseltamivir (Drug)
Panel C: Oseltamivir Treatment (Part 2)
Placebo oseltamivir Day 0 PM through Day 1 PM, oseltamivir 75 mg plus placebo so the total number of capsules is always 4 per dose every 12 hours Day 2 AM through Day 6 PM
Intervention: Influenza A Virus (Biological)
Panel D: Molnupiravir Placebo (Part 2)
Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM
Intervention: Placebo molnupiravir (Drug)
Panel D: Molnupiravir Placebo (Part 2)
Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM
Intervention: Influenza A Virus (Biological)
Virus Inoculation (Part 1 & 2)
Influenza A challenge virus given once by intranasal administration
Intervention: Influenza A Virus (Biological)
Outcomes
Primary Outcomes
Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) From Day 1 PM Through Day 8 AM
Time Frame: From Day 1 PM up to Day 8 post viral inoculation
Infectivity rate was defined as the number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus (A/France/759/21 \[H1N1\] strain) qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from baseline (day 1 PM - afternoon) up to planned discharge from quarantine (day 8 AM - post viral inoculation) is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) From Day 2 PM Through Day 8 AM
Time Frame: From Day 2 PM up to Day 8 post viral inoculation
The number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from day 2 PM up to day 8 post viral inoculation is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
Part 1: Number of Participants Experiencing ≥1 Viral Challenge-related Adverse Event (AE)
Time Frame: Up to approximately 31 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is viral challenge-related as determined by the investigator. Number of participants experiencing ≥1 viral challenge-related AE in part 1 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
Part 2: Peak Viral Load (PVL) Determined by Quantitative Viral Culture Tissue Culture Infective Dose 50% (TCID50) Assay From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)
Time Frame: From Day 1 PM up to Day 8 post viral inoculation
PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). PVL as determined by quantitative viral culture (QVC) was measured starting from day 1 PM (baseline) up to planned discharge from quarantine (day 8 AM). PVL of the H1N1 strain was measured by quantitative viral culture (QVC) using TCID50 plaque assay and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.
Part 2: Area Under the Viral Load-Time Curve (VL-AUC) Determined by QVC (TCID50 Assay) From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)
Time Frame: Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 2 AM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.
Secondary Outcomes
- Part 1: Duration in Days of Quantifiable Influenza Infection by QVC (TCID50 Assay) Confirmed Infection From Day 1 PM Through Day 8 AM After Intranasal Inoculation(From Day 1 PM up to Day 8 post viral inoculation)
- Part 1: QVC-Confirmed Influenza Infection From Day 1 PM Through Day 8 AM After Intranasal Inoculation(From Day 1 PM up to Day 8 post viral inoculation)
- Part 1: QVC-Confirmed Influenza Infection From Day 2 PM Through Day 8 AM After Intranasal Inoculation(From Day 2 PM Up to Day 8 post viral inoculation)
- Part 1: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 1: VL-AUC Determined by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation(Day 2 PM, Days 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 1: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 1: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 2 PM Through Day 8 AM After Intranasal Inoculation(Day 2 PM, Days 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 1: PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation(From Day 1 PM up to Day 8 post viral inoculation)
- Part 1: PVL Determined by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation(From Day 2 PM up to Day 8 post viral inoculation)
- Part 1: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation(From Day 1 PM up to Day 8 post viral inoculation)
- Part 1: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 2 PM Through Day 8 AM After Intranasal Inoculation(From Day 2 PM up to Day 8 post viral inoculation)
- Part 1: Duration in Days of Quantifiable Influenza Infection by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation(From Day 1 PM up to Day 8 post viral inoculation)
- Part 1: Duration in Days of Quantifiable Influenza Infection by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation(From Day 2 PM up to Day 8 post viral inoculation)
- Part 1: Duration in Days of Quantifiable Influenza Infection by QVC Confirmed Infection From Day 2 PM Through Day 8 AM After Intranasal Inoculation(From Day 2 PM up to Day 8 post viral inoculation)
- Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) From Day 2 AM Through Day 8 AM After Intranasal Inoculation(From Day 2 AM up to Day 8 post viral inoculation)
- Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 1: Duration in Days of Grade ≥2 Symptoms From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 1: Peak Total Symptom Score (TSS) From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 1: Peak Total Symptom Score (TSS) From Day 2 AM Through Day 8 AM After Intranasal Inoculation(From Day 2 AM up to Day 8 post viral inoculation)
- Part 1: Daily Maximum TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 1: Duration of Grade ≥2 Symptoms From Day 2 AM Through Day 8 AM After Intranasal Inoculation(From Day 2 AM up to Day 8 post viral inoculation)
- Part 1: Time to Symptom Resolution From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 1: Time to Symptom Resolution From Day 2 AM Through Discharge From Quarantine (Day 8 AM) After Intranasal Inoculation(From Day 2 AM up to Day 8 post viral inoculation)
- Part 1: Time to Peak TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With qRT-PCR-Confirmed Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With qRT-PCR-Confirmed Symptomatic Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With qRT-PCR-Confirmed Moderately Severe Symptomatic Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With qRT-PCR-Confirmed Febrile Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With QVC Confirmed Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculations (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Percentage of Participants With QVC Confirmed Symptomatic Influenza Infection From Day 1 PM up to Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Duration of Quantifiable Infection Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Duration of Quantifiable Infection Determined by QVC From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Time to Confirmed Negative Test Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Time to Confirmed Negative Test Determined by QVC (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculations (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Time to PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM Up to Day 8 post viral inoculation)
- Part 2: Time to PVL Determined by QVC From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Discharge Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation)
- Part 2: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Duration of Quantifiable Infection Determined by qRT-PCR From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Duration of Quantifiable Infection Determined by QVC From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time to Confirmed Negative Test Determined by qRT-PCR From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time to Confirmed Negative Test Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Time in Days to Confirmed Negative Test Determined by QVC From Day 2 AM Through Day 8 AM After Intranasal Inoculations (Molnupiravir Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time in Days to Confirmed Negative Test Determined by QVC From Day 2 AM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time to PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 1 PM up to Day 8 post viral inoculation)
- Part 2: Time to PVL Determined by QVC From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Total Symptom Score AUC (TSS-AUC) From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Total Symptom Score AUC (TSS-AUC) From Day 2 AM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Peak TSS From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Peak TSS From Day 2 AM Through Day 8 AM After Intranasal Inoculation (OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Daily Maximum TSS From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Daily Maximum TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Duration of Grade ≥2 Symptoms From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time to Symptom Resolution From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Time to Peak TSS From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx, OTV Tx and Placebo)(From Day 2 AM up to Day 8 post viral inoculation)
- Part 2: Total Symptom Score AUC (TSS-AUC) From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Peak TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Duration of Grade ≥2 Symptoms From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Time to Symptom Resolution From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Time to Peak TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)(From Day 1 AM up to Day 8 post viral inoculation)
- Part 2: Number of Participants With One or More AE (Molnupiravir Tx and Molnupiravir PEP)(Up to approximately 31 days)
- Part 2: Number of Participants Discontinuing Study Treatment Due to an AE (Molnupiravir Tx and Molnupiravir PEP)(Up to day 6)
- Number of Participants With One or More Viral Challenge-Related AE(Up to approximately 31 days)
- Part 2: Number of Participants With Concomitant Medication Use From Viral Challenge Through Day 28(From Day 0 up to Day 28)
- Maximum Plasma Concentration (Cmax) of N-hydroxycytidine (NHC)(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post dose)
- Time to Maximum Plasma Concentration (Tmax) of NHC(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post dose)
- Area Under the Plasma Concentration From 0 to 12 Hours Postdose (AUC0-12) of NHC(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12 hours post dose)
- Area Under the Plasma Concentration From Dosing to Last Measurable Concentration (AUC0-Last) of NHC(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post dose)
- Ctrough of NHC(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post dose)
- t1/2 of NHC(Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post dose)