Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Molnupiravir
Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.
Other Names:
Drug: Placebo molnupiravir
Four placebo capsules matched to molnupiravir taken twice daily by mouth.
Biological: Influenza A Virus
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).
|
| Experimental: 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 |
Drug: Molnupiravir
Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.
Other Names:
Drug: Placebo molnupiravir
Four placebo capsules matched to molnupiravir taken twice daily by mouth.
Biological: Influenza A Virus
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).
|
| Active Comparator: 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 |
Drug: Placebo oseltamivir
Placebo capsule matched to oseltamivir taken twice daily by mouth.
Drug: Oseltamivir
One capsule of oseltamivir 75 mg taken twice daily by mouth.
Biological: Influenza A Virus
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).
|
| Placebo Comparator: Panel D: Molnupiravir Placebo (Part 2) Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM |
Drug: Placebo molnupiravir
Four placebo capsules matched to molnupiravir taken twice daily by mouth.
Biological: Influenza A Virus
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).
|
| Experimental: Virus Inoculation (Part 1 & 2) Influenza A challenge virus given once by intranasal administration |
Biological: Influenza A Virus
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).
|
Outcome Measures
Primary Outcome Measures
- Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) Day 1 to Discharge [From Day 1 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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) [From Day 0 to Day 31]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 2 afternoon up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 middle of the day to up to Day 8]
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 [From Day 1 morning up to Day 8]
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
- Part 1: Peak TSS Day 2 to Discharge [From Day 2 middle of the day up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 middle of the day up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 middle of the day up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 middle of the day up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 1 afternoon up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
- Part 2, Panel B & C: Peak TSS Day 2 to Discharge [From Day 2 morning up to Day 8]
Maximum TSS as measured by graded symptom scoring system collected 3 times daily.
- Part 2, Panel A: Daily Maximum TSS Day 1 to Discharge [3 times daily from the morning of Day 1 through Day 8]
Maximum TSS on each day, measured by graded symptom scoring system.
- Part 2, Panel B & C: Daily Maximum TSS Day 2 to Discharge [3 times daily from the morning of Day 1 through Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [From Day 1 morning up to Day 8]
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 [From Day 2 morning up to Day 8]
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 [Up to 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.
- Part 2, Panels A & B: Number of Participants who Discontinue Study Drug Due to an AE [Up to day 8]
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 [Up to 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 investigator.
- Part 2, Panels A & B: Number of Participants with Viral Challenge-Related Concomitant Medication Use [Up to 31 days]
The number of participants who use at least 1 concomitant medication.
- Part 2, Panels A & B: 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 morning dose]
The Cmax of NHC will be reported.
- Part 2, Panels A & B: 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 morning dose]
The Tmax of NHC will be reported.
- Part 2, Panels A & B: Half Life (t1/2) of NHC [Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose]
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 [Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose]
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 [Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose]
The AUC0-last of NHC will be reported.
- Part 2, Panels A & B: Trough Concentration (Ctrough) of NHC [Day (D) 0, D2, D4: predose D5: predose, 0.5, 1.5, 4, 8, 12, 24, 48, 72 hours post morning dose]
The Ctrough of NHC will be reported.
Eligibility Criteria
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/m2 and ≤35 kg/m2.
-
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 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 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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 4482-019