Respiratory Syncytial Viruses
Conditions
Brief summary
The purpose of this study is to characterize the Pharmacokinetic and to confirm the popPK model derived from healthy volunteers in hospitalized adults who are infected with respiratory syncytial virus (RSV) and to determine in adults who are hospitalized with respiratory syncytial virus (RSV) infection the dose response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.
Detailed description
The study will be conducted in 3 phases: a screening phase, a treatment phase from Day 1 to Day 5/6 (depending on the timing of the loading dose), and a follow-up phase for a total of 28 days post randomization. Participants will have assessments completed at Day 7, Day 10, Day 14, and Day 28. Depending on discharge date, assessments will be completed either while hospitalized or during outpatient visits. The duration of the participant's participation will be approximately 28 days. The study will be performed in 2 parts. Participants will be randomly assigned to one of 2 treatment groups in part 1, and to one of 3 treatment groups in part 2. Treatment groups will be evaluated for PK and safety after a target of approximately 24 participants have been enrolled in part 1 and before initiating part 2 (approximately 90 participants in part 2). An Independent Data Monitoring Committee (IDMC) will be established to monitor the safety of participants and will review data in an unblinded manner on a regular basis to ensure the continuing safety of the participants enrolled in this study and to evaluate whether efficacy objectives are met. The committee will meet periodically to review interim data. Based on the recommendations of the IDMC following interim analyses/reviews, an increase in duration may be implemented.
Interventions
DRUGlumicitabine
Oral administration of lumicitabine as tablet.
DRUGPlacebo
Oral administration of matching placebo.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized (or in emergency room prior to hospitalization) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization * Diagnosed with respiratory syncytial virus (RSV) infection based on polymerase chain reaction (PCR)-based assay with or without co infection with another respiratory pathogen (eg, influenza, human metapneumovirus, or bacteria) * With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population and/or the RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator * A woman must have a negative urine beta human chorionic gonadotropin at screening * A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug * Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies A woman must be of non-childbearing potential defined as either: a) Postmenopausal: a postmenopausal state is defined as more than (\>) 45 years and no menses for 12 consecutive months without an alternative medical cause, OR Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy. b) Of childbearing potential and, if heterosexually active, also included: practicing a highly effective method of contraception (failure rate of less than (\<) 1percent (%) per year when used consistently and correctly) * Participants must have a body weight of at least 50.0 kilogram, at screening
Exclusion criteria
* Participants who are not expected to survive for more than 48 hours * Participants who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization * Participants who are considered by the investigator to be immuno-compromised within the past 12 months, whether due to underlying medical condition (example, malignancy or genetic disorder) or medical therapy (example, medications other than corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD) or asthma exacerbations, chemotherapy, radiation, stem cell or solid organ transplant) * Participants with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis * Participants undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation) of (\<) 60 milliliters per minute (mL/min) per 1.73 meter square (m\^2) * Participants with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table: Hemoglobin \<9.5 gram per deciliter (g/dL), Platelet count \<75,000 per millimeter cube (/mm\^³), White blood cell count \<1,000/mm\^³, Absolute neutrophil count \<1,000/mm\^³
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1 | Day 1 | Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5 | Day 5 | Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1 | Day 1 | AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5 | Day 5 | AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1 | Day 1 | Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5 | Day 5 | Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine. |
| Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 1 (Baseline) to 7 | RSV RNA viral load in log10 copies/milliliter/day (log10 copies/mL/day) was measured in mid-turbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Due to early termination of study, the analysis was not conducted as planned. Instead, using the same specification as for the primary analysis, a comparison was made on the AUC(1-7) days of pooled active treatment groups versus pooled placebo. The comparison was done as planned using a mixed model for repeated measures, using all available viral load data of baseline up to and including Day 7. The model computes the AUC at group level based on all available data, taking missing data into account under the missing at random assumption. The table reports the planned difference versus (pooled) placebo. No adjustment for multiplicity was applied. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Hospital Stay From Admission to Readiness for Discharge | Up to 28 Days | It is the time from hospital admission to readiness for discharge in hours, with readiness for discharge defined by the investigator. |
| Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment | Up to 28 Days | Number of participants who required to be admitted to the ICU since initiation of treatment were reported. |
| Duration of Intensive Care Unit Stay | Up to 28 Days | In the event that a participant required ICU since initiation of treatment, the duration for how long the participant remained in the ICU was measured. |
| Number of Participants Who Required Supplemental Oxygen | Up to 28 Days | Number of participants who required supplemental oxygen were reported. |
| Time to End of Oxygen Supplementation | Up to 28 Days | It is the time from first dose of study drug to the last end date and time of any oxygen supplementation in hours. |
| Time (Number of Hours) Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=) 93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to the Onset of Respiratory Symptoms | Up to 28 Days | Time (number of hours) until SpO2 \>= 93% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms was reported. |
| Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate | Up to 28 Days | It is the time from first dose of study drug until the time to return to pre-RSV disease level for respiratory rate. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal. |
| Time to Return to Pre-RSV Disease Level for Oxygen Saturation | Up to 28 Days | It is the time from first dose of study drug until the time to return to pre-RSV disease level for oxygen saturation. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal. |
| Time to Return to Pre-RSV Disease Level for Body Temperature | Up to 28 Days | It is the time from first dose of study drug until the time to return to pre-RSV disease level for body temperature. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal. |
| Number of Participants Who Required Noninvasive Mechanical Ventilation Support | Up to 28 Days | Number of participants who required noninvasive mechanical ventilation support (that is supplemental oxygen \[excluding mechanical ventilation\]) were reported. |
| Time to End of Noninvasive Mechanical Ventilation Support | Up to 28 Days | It is the time from first dose of study drug to the last end date and time of noninvasive mechanical ventilation support in hours. |
| Number of Participants Who Required Invasive Mechanical Ventilation Support | Up to 28 Days | Number of participants who required invasive mechanical ventilation support were reported. |
| Time to End of Invasive Mechanical Ventilation Support | Up to 28 Days | It is the time from first dose of study drug to the last end date and time of invasive mechanical ventilation support in hours. |
| Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score | Up to 28 Days | It is the time from first dose of study drug until the time to return to pre-RSV functional status. Functional status is the total points on the KATZ index of independence in activities of daily living (KATZ ADL score). Katz activities of daily living assessed questions related to bathing, dressing, toileting, transferring, continence and feeding components. Total score was calculated by adding the scores for all 6 activities which ranges from 0 high (participant independent) to 6 low (participant very dependent). If one or more component was missing, then the KATZ ADL score was not calculated. The return to pre-RSV functional status occurs at the timepoint where for the first time the KATZ ADL score is equal or higher than the pre-RSV KATZ ADL score and after which no scores lower than the pre-RSV KATZ ADL score occur anymore. |
| Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube | Up to 28 Days | Number of participants who required hydration or feeding by IV catheter or nasogastric tube were reported. |
| Time to Clinical Stability | Up to 28 Days | Time to clinical stability is defined as the time from first dose of study drug until the time at which the following criteria were all met: normalization of blood oxygen level (return to baseline; by pulse oximetry) without requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate and normalization of heart rate. |
| Number of Participants in Each Ordinal Scale Category | Day 5/6 (Day of last study treatment) | Number of participants in each ordinal scale category were reported. Ordinal scale consists of 6 categories or clinical states that are exhaustive, mutually exclusive, and ordered: category 1) death; category 2) admitted to ICU; category 3) non-ICU hospitalization requiring supplemental oxygen; category 4) non-ICU hospitalization not requiring supplemental oxygen; category 5) not hospitalized, unable to resume normal activities; category 6) not hospitalized, resumption of normal activities. |
| Number of Participants With All-Cause Mortality | Up to 28 Days | All-cause mortality included all deaths of participants due to any cause. |
| Number of Participants With Adverse Events (AEs) | Up to 28 Days | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. |
| Peak Viral Load | Up to 28 Days | Peak Viral load is the highest value of log10 viral load at or after the baseline measurement. Peak viral load over time was measured by qRT-PCR. |
| Time to Peak Viral Load | Up to 28 Days | Time to peak viral load is the time from initiation of study treatment until the first time point with the peak viral load. |
| Rate of Decline of Viral Load | Up to 28 Days | Rate of decline of viral load over the first 24 hours calculated as a log decline/24 hours defined as: 24-hour log viral load after first dose of study drug minus (-) log viral load at baseline divided by (/) date/time of 24-hour viral load sample - date/time of baseline viral load. |
| Time to RSV RNA Viral Load Being Undetectable | Up to 28 Days | It is the time in hours from initiation of study treatment until the first post baseline time point at which the virus is undetectable in an assessment and after which time no detectable virus assessment follows as measured by qRT-PCR. |
| Number of Participants With Undetectable Viral Load | Up to 28 Days | Number of participants with undetectable viral load up to 28 days were reported. |
| RSV RNA Viral Load AUC up to Day 14 | Up to Day 14 | RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling. |
| RSV RNA Viral Load AUC in Participants Assigned to a Longer Dosing Duration | Up to 1 Day after the last dose of study drug | RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling. |
| Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences | Baseline up to 28 Days | Number of participants with postbaseline changes in the RSV polymerase L gene and other regions of the RSV genome compared with baseline sequences were reported. |
| RSV RNA Viral Load Over Time | Days 2, 3, 4, 5, 6, 7, 10, 14, and 28 | Antiviral activity RSV RNA viral load was measured in mid-turbinate nasal swabs (obtained from non-intubated participants) or in mid-turbinate nasal swabs and endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using qRT-PCR performed at the central laboratory. |
| Number of Participants With Vital Sign Abnormalities | Up to 28 Days | Number of participants with vital sign (systolic and diastolic blood pressure \[BP\], pulse rate, respiratory rate, temperature and oxygen saturation) abnormalities were reported. For systolic BP: abnormally low refers to less than or equal to (\<=) 90 millimeter of mercury (mmHg); for diastolic BP: abnormally low refers to \<= 50 mmHg; for pulse rate abnormally low refers to less than (\<) 45 beats per minutes (bpm) and abnormally high refers to greater than or equal to (\>=) 120 bpm; for temperature in degree Celsius abnormally high refers to greater than (\>) 37.8 (tympanic), \>38.0 (forehead), \>38.0 (oral), \>37.2 (rectal), \>38.0 (axillary); for oxygen saturation in percentage (%) abnormally low refers to \< 95. Grade 1 = mild; grade 2 = moderate; grade 3 = severe. |
| Number of Participants With QT Interval Abnormalities | Up to 28 Days | Number of participants with QT interval abnormalities (prolonged) were reported. |
| Number of Participants With Clinical Laboratory Abnormalities | Up to 28 Days | Number of participants with clinical laboratory (serum chemistry and hematology) abnormalities were reported. Abbreviations; Erythrocyte MCHC = Erythrocyte Mean Corpuscular Hemoglobin Concentration; Erythrocyte MCH = Erythrocyte Mean Corpuscular Hemoglobin; Ery. = Erythrocyte |
| Time of Hospital Stay From Study Treatment Initiation to Discharge | From study treatment initiation to discharge (Up to 28 Days) | It is the time from treatment initiation to hospital discharge in hours. |
| Time of Hospital Stay From Admission to Discharge | From admission to discharge (Up to 28 Days) | It is the time from hospital admission to hospital discharge in hours. |
| Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge | From study treatment initiation to readiness for discharge on Day 2 or up to Day 6 if hospitalization is prolonged | It is the time from study treatment initiation to readiness for discharge in hours, with readiness for discharge defined by the investigator. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, France, Germany, Japan, Malaysia, Mexico, Netherlands, Poland, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Sponsor halted screening and enrollment in study on 22 June 2018 due to emerging lumicitabine nonclinical data. On 17 October 2018, study was stopped prematurely by sponsor as a precautionary measure, to allow further evaluation of new nonclinical pharmacokinetic (PK) and safety findings and determine their relevance to human studies.
Pre-assignment details
A total of 49 participants were randomized and treated (2 participants in Part 0, 36 participants in Part 1 and 11 participants in Part 2). Analyses were conducted on pooled groups across the 3 study parts.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single loading dose (LD) (Dose 1) of matching placebo tablet orally on Day 1 followed by nine maintenance doses (MD) (Doses 2 to 10) of matching placebo tablets orally twice daily (bid) from Day 1/2 to Day 5/6 (depending on the timing of the LD administration). | 16 |
| 750 mg LD / 250 mg MD Lumicitabine Participants received a single 750 milligram (mg) LD (Dose 1) of lumicitabine tablet orally followed by nine MD (Doses 2 to 10) of 250 mg lumicitabine tablets orally bid from Day 1/2 to Day 5/6 (depending on the timing of the LD administration). | 27 |
| 1000 mg LD / 500 mg MD Lumicitabine Participants received a single 1000 mg LD (Dose 1) of lumicitabine tablet orally followed by nine MD (Doses 2 to 10) of 500 mg lumicitabine tablets orally bid from Day 1/2 to Day 5/6 (depending on the timing of the LD administration). | 6 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | 1000 mg LD / 500 mg MD Lumicitabine | Total | Placebo | 750 mg LD / 250 mg MD Lumicitabine |
|---|---|---|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 18.46 | 66.3 years STANDARD_DEVIATION 17.54 | 65.5 years STANDARD_DEVIATION 17.94 | 66.3 years STANDARD_DEVIATION 17.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 45 Participants | 14 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 18 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 29 Participants | 12 Participants | 14 Participants |
| Region of Enrollment ARGENTINA | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment AUSTRALIA | 1 Participants | 7 Participants | 3 Participants | 3 Participants |
| Region of Enrollment FRANCE | 0 Participants | 7 Participants | 1 Participants | 6 Participants |
| Region of Enrollment JAPAN | 3 Participants | 9 Participants | 3 Participants | 3 Participants |
| Region of Enrollment MALAYSIA | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment POLAND | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment SOUTH KOREA | 0 Participants | 4 Participants | 1 Participants | 3 Participants |
| Region of Enrollment SPAIN | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment SWEDEN | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Region of Enrollment TAIWAN | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment UNITED KINGDOM | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment UNITED STATES | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 5 Participants | 19 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 30 Participants | 11 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 27 | 0 / 6 |
| other Total, other adverse events | 6 / 16 | 17 / 27 | 5 / 6 |
| serious Total, serious adverse events | 2 / 16 | 4 / 27 | 1 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 1
Population: PK analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1 | 9936 nanogram*hour per milliliter (ng*h/mL) | Standard Deviation 2090 |
| 1000 mg LD / 500 mg MD Lumicitabine | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1 | 17120 nanogram*hour per milliliter (ng*h/mL) | Standard Deviation 4330 |
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 5
Population: PK analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5 | 7557 ng*h/mL | Standard Deviation 1525 |
| 1000 mg LD / 500 mg MD Lumicitabine | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5 | 13300 ng*h/mL | Standard Deviation 4603 |
Primary
Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7])
RSV RNA viral load in log10 copies/milliliter/day (log10 copies/mL/day) was measured in mid-turbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Due to early termination of study, the analysis was not conducted as planned. Instead, using the same specification as for the primary analysis, a comparison was made on the AUC(1-7) days of pooled active treatment groups versus pooled placebo. The comparison was done as planned using a mixed model for repeated measures, using all available viral load data of baseline up to and including Day 7. The model computes the AUC at group level based on all available data, taking missing data into account under the missing at random assumption. The table reports the planned difference versus (pooled) placebo. No adjustment for multiplicity was applied.
Time frame: Day 1 (Baseline) to 7
Population: Intent-to-treat-infected (ITT-i) set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 3 | -1.4 log10 copies/mL/day |
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 4 | -2.1 log10 copies/mL/day |
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 5 | -2.5 log10 copies/mL/day |
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 6 | -2.5 log10 copies/mL/day |
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 7 | -2.8 log10 copies/mL/day |
| 750 mg LD / 250 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 2 | -0.3 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 2 | -1.4 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 3 | -1.9 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 6 | -2.7 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 7 | -2.8 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 4 | -2.2 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 5 | -2.5 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 4 | -1.8 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 5 | -1.3 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 2 | -2.5 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 6 | -3.1 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 3 | -1.9 log10 copies/mL/day |
| 1000 mg LD / 500 mg MD Lumicitabine | Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7]) | Day 7 | -3.3 log10 copies/mL/day |
95% CI: [-0.89, 0.24]
95% CI: [-1.33, 0.62]
Primary
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1 | 1845 nanogram per milliliter (ng/mL) | Standard Deviation 545.2 |
| 1000 mg LD / 500 mg MD Lumicitabine | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1 | 2801 nanogram per milliliter (ng/mL) | Standard Deviation 1509 |
Primary
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 5
Population: PK analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5 | 745.4 ng/mL | Standard Deviation 164.2 |
| 1000 mg LD / 500 mg MD Lumicitabine | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5 | 1145 ng/mL | Standard Deviation 440.8 |
Primary
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 1
Population: PK analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1 | 93.7 ng/mL | Standard Deviation 44.16 |
| 1000 mg LD / 500 mg MD Lumicitabine | Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1 | 184.4 ng/mL | Standard Deviation 70.66 |
Primary
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time frame: Day 5
Population: PK analysis was performed on safety set which included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5 | 148.3 ng/mL | Standard Deviation 60.41 |
| 1000 mg LD / 500 mg MD Lumicitabine | Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5 | 281.3 ng/mL | Standard Deviation 156.6 |
Secondary
Duration of Intensive Care Unit Stay
In the event that a participant required ICU since initiation of treatment, the duration for how long the participant remained in the ICU was measured.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Overall number of participants analyzed is 0, since none of the participants were admitted to ICU since initiation of treatment.
Secondary
Number of Participants in Each Ordinal Scale Category
Number of participants in each ordinal scale category were reported. Ordinal scale consists of 6 categories or clinical states that are exhaustive, mutually exclusive, and ordered: category 1) death; category 2) admitted to ICU; category 3) non-ICU hospitalization requiring supplemental oxygen; category 4) non-ICU hospitalization not requiring supplemental oxygen; category 5) not hospitalized, unable to resume normal activities; category 6) not hospitalized, resumption of normal activities.
Time frame: Day 5/6 (Day of last study treatment)
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 1 | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 2 | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 3 | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 4 | 6 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 5 | 5 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 6 | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 6 | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 1 | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 4 | 8 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 5 | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 2 | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 3 | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 2 | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 3 | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 6 | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 4 | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 1 | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants in Each Ordinal Scale Category | Category 5 | 1 Participants |
Secondary
Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
Number of participants who required hydration or feeding by IV catheter or nasogastric tube were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube | 1 Participants |
Secondary
Number of Participants Who Required Invasive Mechanical Ventilation Support
Number of participants who required invasive mechanical ventilation support were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
Secondary
Number of Participants Who Required Noninvasive Mechanical Ventilation Support
Number of participants who required noninvasive mechanical ventilation support (that is supplemental oxygen \[excluding mechanical ventilation\]) were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants Who Required Noninvasive Mechanical Ventilation Support | 14 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Noninvasive Mechanical Ventilation Support | 18 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Noninvasive Mechanical Ventilation Support | 4 Participants |
Secondary
Number of Participants Who Required Supplemental Oxygen
Number of participants who required supplemental oxygen were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants Who Required Supplemental Oxygen | 14 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Supplemental Oxygen | 18 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required Supplemental Oxygen | 4 Participants |
Secondary
Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment
Number of participants who required to be admitted to the ICU since initiation of treatment were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
Time frame: Up to 28 Days
Population: Safety set included all participants who received at least 1 dose of study drug, analyzed as treated. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Adverse Events (AEs) | 7 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Adverse Events (AEs) | 22 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Adverse Events (AEs) | 5 Participants |
Secondary
Number of Participants With All-Cause Mortality
All-cause mortality included all deaths of participants due to any cause.
Time frame: Up to 28 Days
Population: Safety set included all participants who received at least 1 dose of study drug, analyzed as treated. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With All-Cause Mortality | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With All-Cause Mortality | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With All-Cause Mortality | 0 Participants |
Secondary
Number of Participants With Clinical Laboratory Abnormalities
Number of participants with clinical laboratory (serum chemistry and hematology) abnormalities were reported. Abbreviations; Erythrocyte MCHC = Erythrocyte Mean Corpuscular Hemoglobin Concentration; Erythrocyte MCH = Erythrocyte Mean Corpuscular Hemoglobin; Ery. = Erythrocyte
Time frame: Up to 28 Days
Population: Safety set included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'n' (number analyzed) signifies number of participants evaluable for specified categories. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Eosinophils : High | 3 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : High | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCHC : Low | 1 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Indirect Bilirubin : Low | 1 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : High | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : Low | 1 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : High | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate: High | 3 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : High | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase : Low | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes : Low | 5 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : Low | 1 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : High | 5 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Direct Bilirubin : High | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : High | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : High | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : Low | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase ; High | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : Low | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Basophils : High | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase ; High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate : Low | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : Low | 4 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : High | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : Low | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Direct Bilirubin : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : High | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : High | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Indirect Bilirubin : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : Low | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : High | 9 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Basophils : High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Eosinophils : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCHC : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : High | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : High | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes : Low | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase : Low | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate: High | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : High | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : Low | 5 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : High | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Bicarbonate: High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Chloride : High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase : Low | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Creatine Kinase ; High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Direct Bilirubin : High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Indirect Bilirubin : Low | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Basophils : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Eosinophils : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCHC : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes MCH : High | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Erythrocytes : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Ery. Distribution Width : High | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : Low | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Hematocrit : High | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : High | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Monocyte : High | 3 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : Low | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes : High | 4 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Reticulocytes/Erythrocytes : Low | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes : Low | 0 Participants |
Secondary
Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences
Number of participants with postbaseline changes in the RSV polymerase L gene and other regions of the RSV genome compared with baseline sequences were reported.
Time frame: Baseline up to 28 Days
Population: Analysis was performed on ITT-i set. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
Secondary
Number of Participants With QT Interval Abnormalities
Number of participants with QT interval abnormalities (prolonged) were reported.
Time frame: Up to 28 Days
Population: Safety set included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With QT Interval Abnormalities | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With QT Interval Abnormalities | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With QT Interval Abnormalities | 0 Participants |
Secondary
Number of Participants With Undetectable Viral Load
Number of participants with undetectable viral load up to 28 days were reported.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Undetectable Viral Load | 14 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Undetectable Viral Load | 19 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Undetectable Viral Load | 5 Participants |
Secondary
Number of Participants With Vital Sign Abnormalities
Number of participants with vital sign (systolic and diastolic blood pressure \[BP\], pulse rate, respiratory rate, temperature and oxygen saturation) abnormalities were reported. For systolic BP: abnormally low refers to less than or equal to (\<=) 90 millimeter of mercury (mmHg); for diastolic BP: abnormally low refers to \<= 50 mmHg; for pulse rate abnormally low refers to less than (\<) 45 beats per minutes (bpm) and abnormally high refers to greater than or equal to (\>=) 120 bpm; for temperature in degree Celsius abnormally high refers to greater than (\>) 37.8 (tympanic), \>38.0 (forehead), \>38.0 (oral), \>37.2 (rectal), \>38.0 (axillary); for oxygen saturation in percentage (%) abnormally low refers to \< 95. Grade 1 = mild; grade 2 = moderate; grade 3 = severe.
Time frame: Up to 28 Days
Population: Safety set included all participants who received at least 1 dose of study drug, analyzed as treated. Here 'n' (number analyzed) signifies number of participants evaluable for specified categories. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 2 or moderate) | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 1 or mild) | 5 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Oxygen Saturation (Abnormally low) | 7 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 1 or mild) | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 2 or moderate) | 3 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 2 or moderate) | 5 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Pulse Rate (Abnormally high) | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 3 or severe) | 0 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 3 or severe) | 1 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Temperature (Abnormally high) | 4 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 1 or mild) | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 3 or severe) | 3 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Abnormally low) | 2 Participants |
| 750 mg LD / 250 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Abnormally low) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 1 or mild) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Abnormally low) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 1 or mild) | 6 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 2 or moderate) | 4 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 3 or severe) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Abnormally low) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 1 or mild) | 8 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 2 or moderate) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 3 or severe) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Pulse Rate (Abnormally high) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 2 or moderate) | 6 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 3 or severe) | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Temperature (Abnormally high) | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Oxygen Saturation (Abnormally low) | 9 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 1 or mild) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Abnormally low) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 1 or mild) | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 2 or moderate) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 3 or severe) | 1 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Abnormally low) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Respiratory Rate (Grade 3 or severe) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Systolic BP (Grade 2 or moderate) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Oxygen Saturation (Abnormally low) | 2 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 3 or severe) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 2 or moderate) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Temperature (Abnormally high) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Pulse Rate (Abnormally high) | 0 Participants |
| 1000 mg LD / 500 mg MD Lumicitabine | Number of Participants With Vital Sign Abnormalities | Diastolic BP (Grade 1 or mild) | 1 Participants |
Secondary
Peak Viral Load
Peak Viral load is the highest value of log10 viral load at or after the baseline measurement. Peak viral load over time was measured by qRT-PCR.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
Rate of Decline of Viral Load
Rate of decline of viral load over the first 24 hours calculated as a log decline/24 hours defined as: 24-hour log viral load after first dose of study drug minus (-) log viral load at baseline divided by (/) date/time of 24-hour viral load sample - date/time of baseline viral load.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
RSV RNA Viral Load AUC in Participants Assigned to a Longer Dosing Duration
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
Time frame: Up to 1 Day after the last dose of study drug
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. No participant received extended treatment, therefore data was not analyzed.
Secondary
RSV RNA Viral Load AUC up to Day 14
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
Time frame: Up to Day 14
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
RSV RNA Viral Load Over Time
Antiviral activity RSV RNA viral load was measured in mid-turbinate nasal swabs (obtained from non-intubated participants) or in mid-turbinate nasal swabs and endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using qRT-PCR performed at the central laboratory.
Time frame: Days 2, 3, 4, 5, 6, 7, 10, 14, and 28
Population: Analysis was performed on ITT-i set. Here 'n' (number analyzed) signifies number of participants evaluable for each time point. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 10 | 2.5966 log10 copies/mL | Standard Deviation 1.04644 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 5 | 3.6463 log10 copies/mL | Standard Deviation 1.44056 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 3 | 4.8255 log10 copies/mL | Standard Deviation 1.84651 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 7 | 3.4044 log10 copies/mL | Standard Deviation 1.75773 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 6 | 3.6996 log10 copies/mL | Standard Deviation 1.98383 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 2 | 5.9257 log10 copies/mL | Standard Deviation 1.95951 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 14 | 2.3605 log10 copies/mL | Standard Deviation 1.0022 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 4 | 4.0608 log10 copies/mL | Standard Deviation 1.57493 |
| 750 mg LD / 250 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 28 | 1.9179 log10 copies/mL | Standard Deviation 0.06682 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 28 | 1.9714 log10 copies/mL | Standard Deviation 0.22559 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 2 | 4.7208 log10 copies/mL | Standard Deviation 1.60154 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 3 | 4.3515 log10 copies/mL | Standard Deviation 1.97633 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 4 | 3.9345 log10 copies/mL | Standard Deviation 1.646 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 5 | 3.6206 log10 copies/mL | Standard Deviation 1.71515 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 6 | 3.4313 log10 copies/mL | Standard Deviation 1.577 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 7 | 3.2306 log10 copies/mL | Standard Deviation 1.58432 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 10 | 2.7516 log10 copies/mL | Standard Deviation 1.72825 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 14 | 2.3010 log10 copies/mL | Standard Deviation 1.03732 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 7 | 2.6147 log10 copies/mL | Standard Deviation 0.89779 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 4 | 4.0729 log10 copies/mL | Standard Deviation 1.15419 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 2 | 3.4242 log10 copies/mL | Standard Deviation 1.10867 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 10 | 2.5792 log10 copies/mL | Standard Deviation 1.00954 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 3 | 4.3129 log10 copies/mL | Standard Deviation 0.99078 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 28 | 1.9000 log10 copies/mL | Standard Deviation 0 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 6 | 3.2163 log10 copies/mL | Standard Deviation 1.30083 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 5 | 4.5344 log10 copies/mL | Standard Deviation 0.97473 |
| 1000 mg LD / 500 mg MD Lumicitabine | RSV RNA Viral Load Over Time | Day 14 | 2.1512 log10 copies/mL | Standard Deviation 0.50236 |
Secondary
Time (Number of Hours) Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=) 93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to the Onset of Respiratory Symptoms
Time (number of hours) until SpO2 \>= 93% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms was reported.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
Time of Hospital Stay From Admission to Discharge
It is the time from hospital admission to hospital discharge in hours.
Time frame: From admission to discharge (Up to 28 Days)
Population: Analysis was performed on ITT-i set. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time of Hospital Stay From Admission to Discharge | 192.40 Hours | Standard Deviation 199.363 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Admission to Discharge | 181.97 Hours | Standard Deviation 107.938 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Admission to Discharge | 297.53 Hours | Standard Deviation 348.729 |
Secondary
Time of Hospital Stay From Admission to Readiness for Discharge
It is the time from hospital admission to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Time frame: Up to 28 Days
Population: Analysis was performed on ITT-i set. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time of Hospital Stay From Admission to Readiness for Discharge | 133.41 Hours | Standard Deviation 83.057 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Admission to Readiness for Discharge | 178.82 Hours | Standard Deviation 108.522 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Admission to Readiness for Discharge | 297.13 Hours | Standard Deviation 349.159 |
Secondary
Time of Hospital Stay From Study Treatment Initiation to Discharge
It is the time from treatment initiation to hospital discharge in hours.
Time frame: From study treatment initiation to discharge (Up to 28 Days)
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Discharge | 183.91 Hours | Standard Deviation 217.02 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Discharge | 146.72 Hours | Standard Deviation 94.91 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Discharge | 405.24 Hours | Standard Deviation 294.771 |
Secondary
Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge
It is the time from study treatment initiation to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Time frame: From study treatment initiation to readiness for discharge on Day 2 or up to Day 6 if hospitalization is prolonged
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge | 111.05 Hours | Standard Deviation 78.237 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge | 144.17 Hours | Standard Deviation 96.019 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge | 197.60 Hours | Standard Deviation 256.702 |
Secondary
Time to Clinical Stability
Time to clinical stability is defined as the time from first dose of study drug until the time at which the following criteria were all met: normalization of blood oxygen level (return to baseline; by pulse oximetry) without requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate and normalization of heart rate.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to Clinical Stability | 151.21 Hours | Standard Deviation 266.46 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Clinical Stability | 171.74 Hours | Standard Deviation 261.384 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Clinical Stability | 207.00 Hours | Standard Deviation 282.955 |
Secondary
Time to End of Invasive Mechanical Ventilation Support
It is the time from first dose of study drug to the last end date and time of invasive mechanical ventilation support in hours.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Overall number of participants analyzed is zero, since none of the participants required mechanical ventilation support.
Secondary
Time to End of Noninvasive Mechanical Ventilation Support
It is the time from first dose of study drug to the last end date and time of noninvasive mechanical ventilation support in hours.
Time frame: Up to 28 Days
Population: Population included ITT-i set who required noninvasive mechanical ventilation support. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to End of Noninvasive Mechanical Ventilation Support | 83.92 Hours | Standard Deviation 168.125 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to End of Noninvasive Mechanical Ventilation Support | 139.38 Hours | Standard Deviation 237.584 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to End of Noninvasive Mechanical Ventilation Support | 132.40 Hours | Standard Deviation 288.568 |
Secondary
Time to End of Oxygen Supplementation
It is the time from first dose of study drug to the last end date and time of any oxygen supplementation in hours.
Time frame: Up to 28 Days
Population: Population included ITT-i set who required supplemental oxygen. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to End of Oxygen Supplementation | 83.92 Hours | Standard Deviation 168.125 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to End of Oxygen Supplementation | 139.38 Hours | Standard Deviation 237.584 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to End of Oxygen Supplementation | 132.40 Hours | Standard Deviation 288.568 |
Secondary
Time to Peak Viral Load
Time to peak viral load is the time from initiation of study treatment until the first time point with the peak viral load.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate
It is the time from first dose of study drug until the time to return to pre-RSV disease level for respiratory rate. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate | 64.72 Hours | Standard Deviation 180.542 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate | 47.75 Hours | Standard Deviation 153.293 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate | 196.96 Hours | Standard Deviation 290.694 |
Secondary
Time to Return to Pre-RSV Disease Level for Body Temperature
It is the time from first dose of study drug until the time to return to pre-RSV disease level for body temperature. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.
Secondary
Time to Return to Pre-RSV Disease Level for Oxygen Saturation
It is the time from first dose of study drug until the time to return to pre-RSV disease level for oxygen saturation. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to Return to Pre-RSV Disease Level for Oxygen Saturation | 55.55 Hours | Standard Deviation 85.915 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-RSV Disease Level for Oxygen Saturation | 33.85 Hours | Standard Deviation 57.703 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-RSV Disease Level for Oxygen Saturation | 47.56 Hours | Standard Deviation 106.347 |
Secondary
Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score
It is the time from first dose of study drug until the time to return to pre-RSV functional status. Functional status is the total points on the KATZ index of independence in activities of daily living (KATZ ADL score). Katz activities of daily living assessed questions related to bathing, dressing, toileting, transferring, continence and feeding components. Total score was calculated by adding the scores for all 6 activities which ranges from 0 high (participant independent) to 6 low (participant very dependent). If one or more component was missing, then the KATZ ADL score was not calculated. The return to pre-RSV functional status occurs at the timepoint where for the first time the KATZ ADL score is equal or higher than the pre-RSV KATZ ADL score and after which no scores lower than the pre-RSV KATZ ADL score occur anymore.
Time frame: Up to 28 Days
Population: ITT-i set included all randomly assigned participants who received at least 1 dose of study drug and who had an RSV infection confirmed by a PCR-based assay at the central laboratory at baseline, analyzed as randomized. Analyses were conducted on pooled groups across the 3 study parts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 750 mg LD / 250 mg MD Lumicitabine | Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score | 3.60 Days | Standard Deviation 7.434 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score | 4.48 Days | Standard Deviation 6.961 |
| 1000 mg LD / 500 mg MD Lumicitabine | Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score | 6.00 Days | Standard Deviation 11.203 |
Secondary
Time to RSV RNA Viral Load Being Undetectable
It is the time in hours from initiation of study treatment until the first post baseline time point at which the virus is undetectable in an assessment and after which time no detectable virus assessment follows as measured by qRT-PCR.
Time frame: Up to 28 Days
Population: Data was not collected and analyzed because this study was stopped prematurely.