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Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)

Primary Purpose

Influenza Infection

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Molnupiravir
Placebo molnupiravir
Placebo oseltamivir
Oseltamivir
Influenza A Virus
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza Infection

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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^2. 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.

Sites / Locations

  • hVIVO Services ( Site 0001)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Active Comparator

Placebo Comparator

Experimental

Arm Label

Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2)

Panel B: Molnupiravir Treatment (Part 2)

Panel C: Oseltamivir Treatment (Part 2)

Panel D: Molnupiravir Placebo (Part 2)

Virus Inoculation (Part 1 & 2)

Arm Description

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

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

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

Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM

Influenza A challenge virus given once by intranasal administration

Outcomes

Primary Outcome Measures

Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) Day 1 to Discharge
The proportion of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Part 1: Infectivity Rate Based on qRT-PCR Day 2 to Discharge
The proportion of participants with two quantifiable ≥LLOQ influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Part 1: Number of participants experiencing ≥1 viral challenge-related adverse event (AE)
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 investigator.
Part 2, Panel A: Peak Viral Load (PVL) by Quantitative Viral Culture
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Part 2, Panel B: Area Under the Viral Load-Time Curve (VL-AUC) by Quantitative Viral Culture
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.

Secondary Outcome Measures

Part 1: Quantitative Viral Culture-Confirmed Influenza Infection Day 1 to Discharge
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Part 1: Quantitative Viral Culture-Confirmed Influenza Infection Day 2 to Discharge
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Part 1: VL-AUC by Quantitative Viral Culture Day 1 to Discharge
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Part 1: VL-AUC by qRT-PCR Day 1 to Discharge
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Part 1: VL-AUC by Quantitative Viral Culture Day 2 to Discharge
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Part 1: VL-AUC by qRT-PCR Day 2 to Discharge
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Part 1: PVL by qRT-PCR Day 1 to Discharge
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Part 1: PVL by Quantitative Viral Culture Day 1 to Discharge
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Part 1: PVL by qRT-PCR Day 2 to Discharge
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Part 1: PVL by Quantitative Viral Culture Day 2 to Discharge
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Part 1: Duration of Quantifiable Influenza by qRT-PCR Day 1 to Discharge
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Part 1: Duration of Quantifiable Influenza by Quantitative Viral Culture Day 1 to Discharge
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Part 1: Duration of Quantifiable Influenza by qRT-PCR Day 2 to Discharge
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Part 1: Duration of Quantifiable Influenza by Quantitative Viral Culture Day 2 to Discharge
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) Day 1 to Discharge
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Part 1: TSS-AUC Day 2 to Discharge
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Part 1: Peak Total Symptom Score (TSS) Day 1 to Discharge
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Part 1: Peak TSS Day 2 to Discharge
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Part 1: Duration in Days of Grade ≥2 Symptoms Day 1 to Discharge
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Part 1: Duration in Days of Grade ≥2 Symptoms Day 2 to Discharge
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Part 1: Time in Days to Symptom Resolution Day 1 to Discharge
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Part 1: Time in Days to Symptom Resolution Day 2 to Discharge
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Part 1: Time in Days to Peak Daily Maximum TSS Day 1 to Discharge
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Part 1: Time in Days to Peak Daily Maximum TSS Day 2 to Discharge
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Part 2, Panel A: VL-AUC by Quantitative Viral Culture
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Part 2, Panel A: VL-AUC by qRT-PCR
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Part 2, Panel A: PVL by qRT-PCR
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Part 2, Panel A: qRT-PCR-Confirmed Influenza Infection
The proportion of participants witht wo quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Part 2, Panel A: qRT-PCR-Confirmed Symptomatic Influenza Infection
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND TSS ≥2 at ≥1 time point following inoculation.
Part 2, Panel A: qRT-PCR-Confirmed Moderately Severe Symptomatic Influenza Infection
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND any symptom of Grade ≥2 at ≥1 timepoint following inoculation.
Part 2, Panel A: qRT-PCR-Confirmed Febrile Influenza Infection
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND temperature of ≥37.9 degrees Celsius at ≥1 timepoint following inoculation.
Part 2, Panel A: Quantitative Viral Culture-Confirmed Influenza Infection
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Part 2, Panel A: Quantitative Viral Culture-Confirmed Symptomatic Influenza Infection
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample AND TSS ≥2 at ≥1 timepoint following inoculation.
Part 2, Panel A: Duration of Quantifiable Influenza by qRT-PCR
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Part 2, Panel A: Duration of Quantifiable Influenza by Quantitative Viral Culture
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Part 2, Panel A: Time in Days to Confirmed Negative Test by qRT-PCR
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by qRT-PCR.
Part 2, Panel A: Time in Days to Confirmed Negative Test by Quantitative Viral Culture
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by quantitative viral culture.
Part 2, Panel A: Time in Days to Peak Viral Load by qRT-PCR
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by qRT-PCR.
Part 2, Panel A: Time in Days to Peak Viral Load by Quantitative Viral Culture
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by quantitative viral culture.
Part 2, Panel C: VL-AUC by Quantitative Viral Culture
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Part 2, Panel B & C: VL-AUC by qRT-PCR
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Part 2, Panel B & C: PVL by qRT-PCR
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Part 2, Panel B & C: PVL by Quantitative Viral Culture
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Part 2, Panel B & C: Duration of Quantifiable Influenza by qRT-PCR
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Part 2, Panel B & C: Duration of Quantifiable Influenza by Quantitative Viral Culture
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Part 2, Panel B & C: Time in Days to Confirmed Negative Test by qRT-PCR
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by qRT-PCR.
Part 2, Panel B & C: Time in Days to Confirmed Negative Test by Quantitative Viral Culture
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by quantitative viral culture.
Part 2, Panel B & C: Time in Days to Peak Viral Load by qRT-PCR
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by qRT-PCR.
Part 2, Panel B & C: Time in Days to Peak Viral Load by Quantitative Viral Culture
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by quantitative viral culture.
Part 2, Panel A: TSS-AUC Day 1 to Discharge
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Part 2, Panel B & C: TSS-AUC Day 2 to Discharge
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Part 2, Panel A: Peak TSS Day 1 to Discharge
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Part 2, Panel B & C: Peak TSS Day 2 to Discharge
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Part 2, Panel A: Daily Maximum TSS Day 1 to Discharge
Maximum TSS on each day, measured by graded symptom scoring system.
Part 2, Panel B & C: Daily Maximum TSS Day 2 to Discharge
Maximum TSS on each day, measured by graded symptom scoring system.
Part 2, Panel A: Duration in Days of Grade ≥2 Symptoms Day 1 to Discharge
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Part 2, Panel B & C: Duration in Days of Grade ≥2 Symptoms Day 2 to Discharge
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Part 2, Panel A: Time in Days to Symptom Resolution Day 1 to Discharge
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Part 2, Panel B & C: Time in Days to Symptom Resolution Day 2 to Discharge
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Part 2, Panel A: Time in Days to Peak Daily Maximum TSS Day 1 to Discharge
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Part 2, Panel B & C: Time in Days to Peak Daily Maximum TSS Day 2 to Discharge
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Part 2, Panels A & B: Number of Participants with One or More AE
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.
Part 2, Panels A & B: Number of Participants who Discontinue Study Drug Due to an AE
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.
Part 2, Panels A & B: Number of Participants with One or More Viral Challenge-Related AE
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 investigator.
Part 2, Panels A & B: Number of Participants with Viral Challenge-Related Concomitant Medication Use
The number of participants who use at least 1 concomitant medication.
Part 2, Panels A & B: Maximum Plasma Concentration (Cmax) of N-hydroxycytidine (NHC)
The Cmax of NHC will be reported.
Part 2, Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC
The Tmax of NHC will be reported.
Part 2, Panels A & B: Half Life (t1/2) of NHC
The t1/2 of NHC will be reported.
Part 2, Panels A & B: Area Under the Plasma Concentration From 0 to 12 Hours Postdose (AUC0-12) of NHC
The AUC0-12 of NHC will be reported.
Part 2, Panels A & B: Area Under the Plasma Concentration From 0 to Time of the Last Quantifiable Concentration after Dosing (AUC0-last) of NHC
The AUC0-last of NHC will be reported.
Part 2, Panels A & B: Trough Concentration (Ctrough) of NHC
The Ctrough of NHC will be reported.

Full Information

First Posted
April 5, 2023
Last Updated
August 28, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05818124
Brief Title
Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 21, 2023 (Actual)
Primary Completion Date
March 29, 2024 (Anticipated)
Study Completion Date
March 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2)
Arm Type
Experimental
Arm Description
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
Arm Title
Panel B: Molnupiravir Treatment (Part 2)
Arm Type
Experimental
Arm Description
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
Arm Title
Panel C: Oseltamivir Treatment (Part 2)
Arm Type
Active Comparator
Arm Description
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
Arm Title
Panel D: Molnupiravir Placebo (Part 2)
Arm Type
Placebo Comparator
Arm Description
Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM
Arm Title
Virus Inoculation (Part 1 & 2)
Arm Type
Experimental
Arm Description
Influenza A challenge virus given once by intranasal administration
Intervention Type
Drug
Intervention Name(s)
Molnupiravir
Other Intervention Name(s)
MK-4482
Intervention Description
Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.
Intervention Type
Drug
Intervention Name(s)
Placebo molnupiravir
Intervention Description
Four placebo capsules matched to molnupiravir taken twice daily by mouth.
Intervention Type
Drug
Intervention Name(s)
Placebo oseltamivir
Intervention Description
Placebo capsule matched to oseltamivir taken twice daily by mouth.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Intervention Description
One capsule of oseltamivir 75 mg taken twice daily by mouth.
Intervention Type
Biological
Intervention Name(s)
Influenza A Virus
Intervention Description
Influenza A challenge virus given once by intranasal administration at an inoculum concentration of between approximately 5 and 7 Log10 tissue culture infective dose 50% (TCID50/mL).
Primary Outcome Measure Information:
Title
Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) Day 1 to Discharge
Description
The proportion of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: Infectivity Rate Based on qRT-PCR Day 2 to Discharge
Description
The proportion of participants with two quantifiable ≥LLOQ influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: Number of participants experiencing ≥1 viral challenge-related adverse event (AE)
Description
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 investigator.
Time Frame
From Day 0 to Day 31
Title
Part 2, Panel A: Peak Viral Load (PVL) by Quantitative Viral Culture
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel B: Area Under the Viral Load-Time Curve (VL-AUC) by Quantitative Viral Culture
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Secondary Outcome Measure Information:
Title
Part 1: Quantitative Viral Culture-Confirmed Influenza Infection Day 1 to Discharge
Description
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: Quantitative Viral Culture-Confirmed Influenza Infection Day 2 to Discharge
Description
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: VL-AUC by Quantitative Viral Culture Day 1 to Discharge
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: VL-AUC by qRT-PCR Day 1 to Discharge
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: VL-AUC by Quantitative Viral Culture Day 2 to Discharge
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: VL-AUC by qRT-PCR Day 2 to Discharge
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: PVL by qRT-PCR Day 1 to Discharge
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: PVL by Quantitative Viral Culture Day 1 to Discharge
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: PVL by qRT-PCR Day 2 to Discharge
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: PVL by Quantitative Viral Culture Day 2 to Discharge
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: Duration of Quantifiable Influenza by qRT-PCR Day 1 to Discharge
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: Duration of Quantifiable Influenza by Quantitative Viral Culture Day 1 to Discharge
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 1: Duration of Quantifiable Influenza by qRT-PCR Day 2 to Discharge
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: Duration of Quantifiable Influenza by Quantitative Viral Culture Day 2 to Discharge
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Time Frame
From Day 2 afternoon up to Day 8
Title
Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) Day 1 to Discharge
Description
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Time Frame
From Day 1 morning up to Day 8
Title
Part 1: TSS-AUC Day 2 to Discharge
Description
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Time Frame
From Day 2 middle of the day to up to Day 8
Title
Part 1: Peak Total Symptom Score (TSS) Day 1 to Discharge
Description
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Time Frame
From Day 1 morning up to Day 8
Title
Part 1: Peak TSS Day 2 to Discharge
Description
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Time Frame
From Day 2 middle of the day up to Day 8
Title
Part 1: Duration in Days of Grade ≥2 Symptoms Day 1 to Discharge
Description
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Time Frame
From Day 1 morning up to Day 8
Title
Part 1: Duration in Days of Grade ≥2 Symptoms Day 2 to Discharge
Description
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Time Frame
From Day 2 middle of the day up to Day 8
Title
Part 1: Time in Days to Symptom Resolution Day 1 to Discharge
Description
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Time Frame
From Day 1 morning up to Day 8
Title
Part 1: Time in Days to Symptom Resolution Day 2 to Discharge
Description
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Time Frame
From Day 2 middle of the day up to Day 8
Title
Part 1: Time in Days to Peak Daily Maximum TSS Day 1 to Discharge
Description
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Time Frame
From Day 1 morning up to Day 8
Title
Part 1: Time in Days to Peak Daily Maximum TSS Day 2 to Discharge
Description
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Time Frame
From Day 2 middle of the day up to Day 8
Title
Part 2, Panel A: VL-AUC by Quantitative Viral Culture
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: VL-AUC by qRT-PCR
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: PVL by qRT-PCR
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: qRT-PCR-Confirmed Influenza Infection
Description
The proportion of participants witht wo quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: qRT-PCR-Confirmed Symptomatic Influenza Infection
Description
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND TSS ≥2 at ≥1 time point following inoculation.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel A: qRT-PCR-Confirmed Moderately Severe Symptomatic Influenza Infection
Description
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND any symptom of Grade ≥2 at ≥1 timepoint following inoculation.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel A: qRT-PCR-Confirmed Febrile Influenza Infection
Description
The proportion of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples over 2 days AND temperature of ≥37.9 degrees Celsius at ≥1 timepoint following inoculation.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel A: Quantitative Viral Culture-Confirmed Influenza Infection
Description
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Quantitative Viral Culture-Confirmed Symptomatic Influenza Infection
Description
The proportion of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample AND TSS ≥2 at ≥1 timepoint following inoculation.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel A: Duration of Quantifiable Influenza by qRT-PCR
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Duration of Quantifiable Influenza by Quantitative Viral Culture
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Time in Days to Confirmed Negative Test by qRT-PCR
Description
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Time in Days to Confirmed Negative Test by Quantitative Viral Culture
Description
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Time in Days to Peak Viral Load by qRT-PCR
Description
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by qRT-PCR.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel A: Time in Days to Peak Viral Load by Quantitative Viral Culture
Description
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by quantitative viral culture.
Time Frame
From Day 1 afternoon up to Day 8
Title
Part 2, Panel C: VL-AUC by Quantitative Viral Culture
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: VL-AUC by qRT-PCR
Description
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: PVL by qRT-PCR
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by qRT-PCR.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: PVL by Quantitative Viral Culture
Description
PVL is the maximum viral load of influenza challenge virus from nasopharyngeal samples to be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Duration of Quantifiable Influenza by qRT-PCR
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by qRT-PCR.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Duration of Quantifiable Influenza by Quantitative Viral Culture
Description
Time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples). To be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Confirmed Negative Test by qRT-PCR
Description
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by qRT-PCR.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Confirmed Negative Test by Quantitative Viral Culture
Description
Time in days from the beginning of the specified time frame until the first confirmed unquantifiable (<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples. To be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Peak Viral Load by qRT-PCR
Description
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by qRT-PCR.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Peak Viral Load by Quantitative Viral Culture
Description
Time in days from the beginning of the specified time frame until the peak viral load measurement to be determined by quantitative viral culture.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel A: TSS-AUC Day 1 to Discharge
Description
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel B & C: TSS-AUC Day 2 to Discharge
Description
TSS-AUC as measured by graded symptom scoring system collected 3 times daily. Each symptom is graded where a higher grade represents a higher symptom intensity/impact.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel A: Peak TSS Day 1 to Discharge
Description
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel B & C: Peak TSS Day 2 to Discharge
Description
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel A: Daily Maximum TSS Day 1 to Discharge
Description
Maximum TSS on each day, measured by graded symptom scoring system.
Time Frame
3 times daily from the morning of Day 1 through Day 8
Title
Part 2, Panel B & C: Daily Maximum TSS Day 2 to Discharge
Description
Maximum TSS on each day, measured by graded symptom scoring system.
Time Frame
3 times daily from the morning of Day 1 through Day 8
Title
Part 2, Panel A: Duration in Days of Grade ≥2 Symptoms Day 1 to Discharge
Description
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel B & C: Duration in Days of Grade ≥2 Symptoms Day 2 to Discharge
Description
Duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel A: Time in Days to Symptom Resolution Day 1 to Discharge
Description
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Symptom Resolution Day 2 to Discharge
Description
Time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panel A: Time in Days to Peak Daily Maximum TSS Day 1 to Discharge
Description
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Time Frame
From Day 1 morning up to Day 8
Title
Part 2, Panel B & C: Time in Days to Peak Daily Maximum TSS Day 2 to Discharge
Description
Time in days from the beginning of the specified time frame to the time of the peak daily maximum TSS.
Time Frame
From Day 2 morning up to Day 8
Title
Part 2, Panels A & B: Number of Participants with One or More AE
Description
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.
Time Frame
Up to 31 days
Title
Part 2, Panels A & B: Number of Participants who Discontinue Study Drug Due to an AE
Description
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.
Time Frame
Up to day 8
Title
Part 2, Panels A & B: Number of Participants with One or More Viral Challenge-Related AE
Description
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 investigator.
Time Frame
Up to 31 days
Title
Part 2, Panels A & B: Number of Participants with Viral Challenge-Related Concomitant Medication Use
Description
The number of participants who use at least 1 concomitant medication.
Time Frame
Up to 31 days
Title
Part 2, Panels A & B: Maximum Plasma Concentration (Cmax) of N-hydroxycytidine (NHC)
Description
The Cmax of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose
Title
Part 2, Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC
Description
The Tmax of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose
Title
Part 2, Panels A & B: Half Life (t1/2) of NHC
Description
The t1/2 of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose
Title
Part 2, Panels A & B: Area Under the Plasma Concentration From 0 to 12 Hours Postdose (AUC0-12) of NHC
Description
The AUC0-12 of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose
Title
Part 2, Panels A & B: Area Under the Plasma Concentration From 0 to Time of the Last Quantifiable Concentration after Dosing (AUC0-last) of NHC
Description
The AUC0-last of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose
Title
Part 2, Panels A & B: Trough Concentration (Ctrough) of NHC
Description
The Ctrough of NHC will be reported.
Time Frame
Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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^2. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
hVIVO Services ( Site 0001)
City
London
State/Province
London, City Of
ZIP/Postal Code
E1 2AX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
07958615767

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

Learn more about this trial

Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)

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