MRSA Bacteremia
Conditions
Keywords
MRSA, Staphylococcus aureus bacteremia, SAB, bloodstream infection, BSI, Bacteremia
Brief summary
The objectives of this study is to exploratory whether Vancomycin + Delpazolid is more effective to the standard of treatment (Vancomycin)/ for hospitalized adults with MRSA bacteraemia.
Detailed description
The mortality from S aureus bacteremia is higher for MRSA than for methicillin-susceptible S aureus (MSSA), typically at 20% to 25%. The current standard therapy for MRSA bacteremia is Vancomycin. Vancomycin has many shortcomings, including poor tissue penetration and slow killing time. Vancomycin has reduced efficacy against MRSA and tended to increase the MIC level (called MIC creep). Addition of Delpazolid to Vancomycin could improve the known drawbacks of Vancomycin alone.
Interventions
DRUGDelpazolid
BID, PO
DRUGVancomycin
IV infusion per 2020 IDSA guideline
DRUGPlacebo of Delpazolid
BID, PO
Sponsors
LigaChem Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind with placebo
Intervention model description
Placebo-controlled
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥19 years of age on the date of written consent * Subject who has confirmed positive MRSA at least one set of blood cultures within 72 hours prior to randomization OR, Subject who has confirmed positive MRSA at least one set of blood culture whthin 96 hours prior to randomization and treated with vancomycin at least 72 hours prior to randomization * Subject who has clinical symptoms or signs of MRSA bacteremia according to the judgment of the investigator * Subject who voluntarily decides to participate in this clinical trial after being explained fully, and agrees in writing to implement the clinical trial compliance matters
Exclusion criteria
* Subject with polymicrobial bacteremia or infections including Gram-negative strain * Subject undergoing or in need of treatment with antiviral or antifungal drugs * Subject who has received treatment for MRSA bacteremia within 3 months of screening (Subjects who have re-infection by investigator's judgement may participant in the study.) * Subject who has been administered effective antibiotics against MRSA (Vancomycin, etc.) for more than 96 hours prior to the first investigational product administration. (However, antibiotics effective for MRSA such as vancomycin are allowed to be administered for less than 72 hours.) * Septic shock patients * Subject who has hypersensitivity to vancomycin or linezolid * Subject who has a history of hypersensitivity to peptide-based antibiotics and aminoglycoside-based antibiotics * Subject who is receiving a MAO inhibitor(MAOI) or has received MAOI within 14 days of the first investigational drug administration * Subject taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptan), meperidine, or buspirone * Subject with severely decreased immunity (Severe neutropenia (ANC \<0.5×10\^9/L) etc.) * Subject who is expected to die within 2 days due to serious complications of MRSA bacteremia based on the judgment of the investigator * Body Mass Index (BMI) ≥35 kg/m2 * Subject who is unable to administer drugs orally * Pregnant or lactating female, female or male with childbearing potential who disagrees with the use of appropriate contraceptive methods during the study and up to 14 days after the last dose of the investigator product * Subject who has received other clinical trial drugs within 30 days of screening * Subject who is not suitable for participation in this clinical trial according to the medical findings of investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS | at Day 14 | * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100 |
| Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS | at Day 14 | * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clearance of MRSA bacteremia_PPS | by EOT (up to 6 weeks) | If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed. |
| Mortality From MRSA Bacteremia by EOT_PPS | During the treatment period (from the first administration to EOT (up to 6 weeks)) | * Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100 |
| Relapse Rate of MRSA bacteremia_FAS | from the first administration to TOC (4 weeks after EOT) | * Defined as a positive blood culture to MRSA when previous ones were negative * Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100 |
| Relapse Rate of MRSA bacteremia_PPS | from the first administration to TOC (4 weeks after EOT) | * Defined as a positive blood culture to MRSA when previous ones were negative * Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100 |
| Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks) | * Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test * Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100 |
| Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks) | * Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test * Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100 |
| Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day 3, Day 5, Day 7, Day 14 | * Proportion of participants who have positive results on blood culture tests * Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100 |
| Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day 3, Day 5, Day 7, Day 14 | * Proportion of participants who have positive results on blood culture tests * Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100 |
| Time to Clearance of MRSA bacteremia_FAS | by EOT (up to 6 weeks) | If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed. |
| Overall Cure Rate by End of Treatment (EOT)_FAS | Day 7 visit and EOT (up to 6 weeks) visit | * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100 |
| Overall Cure Rate by End of Treatment (EOT)_PPS | Day 7 visit and EOT (up to 6 weeks) visit | * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100 |
| Mortality From MRSA Bacteremia by EOT_FAS | During the treatment period (from the first administration to EOT (up to 6 weeks)) | * Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) parameters_Cmax,ss | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Cmax,ss: Maximum concentration of drug at steady state) |
| Pharmacokinetics (PK) parameters_Cmin,ss | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Cmin,ss: Minimum concentration of drug at steady state) |
| Pharmacokinetics (PK) parameters_Tmax,ss | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Tmax,ss: Time to reach Cmax at steady state) |
| Pharmacokinetics (PK) parameters_t1/2β | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (t1/2β : Terminal elimination half-life) |
| Pharmacokinetics (PK) parameters_MRT,ss | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (MRT,ss: Mean residence time at steady state) |
| Pharmacokinetics (PK) parameters_AUC,ss | Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product. | Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (AUC,ss: Area under the concentration-time curve at steady state) |
| Delpazolid MIC Levels | Screening (Baseline), Day 14, EOT | Delpazolid minimum inhibitory concentration (MIC) level by broth microdilution (BMD) |
| Vancomycin MIC Level | at Screening visit (baseline) | Vancomycin minimum inhibitory concentration (MIC) levels |
Countries
South Korea
Participant flow
Recruitment details
This study was initiated on 26 Apr 2022 (first signed informed consent) with the date of last participant who completed last study visit on 18 Mar 2024. A total of 45 participants were screened. Of these, 40 participants were randomized to 1 of 2 arms. The remaining 5 participants were considered to have been screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID Vancomycin: IV infusion per 2020 IDSA guideline
* Intravenous Vancomycin dosed as per 2020 IDSA guideline
* Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
* Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin).
Delpazolid: BID, PO | 18 |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid Vancomycin: IV infusion per 2020 IDSA guideline
* Intravenous Vancomycin dosed as per 2020 IDSA guideline
* Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
* Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin).
Placebo of Delpazolid: BID, PO | 20 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | If the following treatment failure criteria are met during treatment period | 1 | 2 |
| Overall Study | When investigators decide that the subject should stop participating in the trial for other reasons | 4 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 13 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 5 Participants | 15 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 16.47 | 69.3 years STANDARD_DEVIATION 9.68 | 66.8 years STANDARD_DEVIATION 13.73 |
| BMI (kg/m2) | 24.229 kg/m^2 STANDARD_DEVIATION 4.6732 | 24.020 kg/m^2 STANDARD_DEVIATION 3.1754 | 24.130 kg/m^2 STANDARD_DEVIATION 3.9823 |
| Childbearing potential No | 8 Participants | 7 Participants | 15 Participants |
| Childbearing potential Yes | 2 Participants | 0 Participants | 2 Participants |
| Height (cm) | 161.85 cm STANDARD_DEVIATION 7.582 | 164.15 cm STANDARD_DEVIATION 6.302 | 162.94 cm STANDARD_DEVIATION 7.009 |
| Primary Lesion Device related | 1 Participants | 0 Participants | 1 Participants |
| Primary Lesion Infective endocarditis | 0 Participants | 2 Participants | 2 Participants |
| Primary Lesion Intravenous line related | 7 Participants | 2 Participants | 9 Participants |
| Primary Lesion Native osteoarticular | 1 Participants | 2 Participants | 3 Participants |
| Primary Lesion Other | 3 Participants | 5 Participants | 8 Participants |
| Primary Lesion Pleuropulmonary infection | 0 Participants | 3 Participants | 3 Participants |
| Primary Lesion Primary blood stream infection | 3 Participants | 1 Participants | 4 Participants |
| Primary Lesion Skin and soft tissue infection | 6 Participants | 1 Participants | 7 Participants |
| Primary Lesion Unknown | 0 Participants | 2 Participants | 2 Participants |
| Primary lesion removable No | 9 Participants | 11 Participants | 20 Participants |
| Primary lesion removable Yes | 11 Participants | 7 Participants | 18 Participants |
| Primary lesion removed No | 5 Participants | 3 Participants | 8 Participants |
| Primary lesion removed Yes | 6 Participants | 4 Participants | 10 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
| Vancomycin MIC <1.5 mcg/mL | 13 Participants | 10 Participants | 23 Participants |
| Vancomycin MIC ≥1.5 mcg/mL | 7 Participants | 8 Participants | 15 Participants |
| Weight (kg) | 63.59 kg STANDARD_DEVIATION 13.256 | 64.77 kg STANDARD_DEVIATION 9.536 | 64.14 kg STANDARD_DEVIATION 11.506 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 20 |
| other Total, other adverse events | 13 / 18 | 16 / 20 |
| serious Total, serious adverse events | 0 / 18 | 1 / 20 |
Outcome results
Primary
Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS
* 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100
Time frame: at Day 14
Population: FAS (Full analysis set) : The analysis was conducted on patients who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS | 9 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS | 10 Participants |
Primary
Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS
* 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100
Time frame: at Day 14
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS | 9 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS | 9 Participants |
Secondary
Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS
* Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test * Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100
Time frame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
Population: FAS (Full analysis set) : The analysis was conducted on participants who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day5 | 9 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day14 | 9 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day7 | 7 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | End of Treatment | 12 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day3 | 8 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | End of Treatment | 14 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day3 | 6 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day5 | 11 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day7 | 6 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS | Day14 | 11 Participants |
Secondary
Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS
* Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test * Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100
Time frame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day3 | 5 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day5 | 8 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day7 | 6 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day14 | 9 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | End of Treatment | 10 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | End of Treatment | 12 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day14 | 10 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day5 | 8 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day3 | 5 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS | Day7 | 5 Participants |
Secondary
Mortality From MRSA Bacteremia by EOT_FAS
* Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100
Time frame: During the treatment period (from the first administration to EOT (up to 6 weeks))
Population: FAS (Full analysis set) : The analysis was conducted on patients who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Mortality From MRSA Bacteremia by EOT_FAS | Overall death | 0 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Mortality From MRSA Bacteremia by EOT_FAS | Death from MRSA bacteremia | 0 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Mortality From MRSA Bacteremia by EOT_FAS | Overall death | 1 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Mortality From MRSA Bacteremia by EOT_FAS | Death from MRSA bacteremia | 0 Participants |
Secondary
Mortality From MRSA Bacteremia by EOT_PPS
* Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100
Time frame: During the treatment period (from the first administration to EOT (up to 6 weeks))
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Mortality From MRSA Bacteremia by EOT_PPS | Overall death | 0 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Mortality From MRSA Bacteremia by EOT_PPS | Death from MRSA bacteremia | 0 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Mortality From MRSA Bacteremia by EOT_PPS | Overall death | 1 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Mortality From MRSA Bacteremia by EOT_PPS | Death from MRSA bacteremia | 0 Participants |
Secondary
Overall Cure Rate by End of Treatment (EOT)_FAS
* 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100
Time frame: Day 7 visit and EOT (up to 6 weeks) visit
Population: FAS (Full analysis set) : The analysis was conducted on patients who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate by End of Treatment (EOT)_FAS | Day 7 | 7 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate by End of Treatment (EOT)_FAS | End of Treatment | 12 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate by End of Treatment (EOT)_FAS | Day 7 | 6 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate by End of Treatment (EOT)_FAS | End of Treatment | 14 Participants |
Secondary
Overall Cure Rate by End of Treatment (EOT)_PPS
* 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100
Time frame: Day 7 visit and EOT (up to 6 weeks) visit
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate by End of Treatment (EOT)_PPS | Day 7 | 6 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Overall Cure Rate by End of Treatment (EOT)_PPS | End of Treatment | 10 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate by End of Treatment (EOT)_PPS | Day 7 | 5 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Overall Cure Rate by End of Treatment (EOT)_PPS | End of Treatment | 12 Participants |
Secondary
Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS
* Proportion of participants who have positive results on blood culture tests * Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100
Time frame: Day 3, Day 5, Day 7, Day 14
Population: FAS (Full analysis set) : The analysis was conducted on participants who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day3 | 6 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day5 | 4 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day7 | 1 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day14 | 0 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day14 | 2 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day3 | 12 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day7 | 3 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS | Day5 | 7 Participants |
Secondary
Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS
* Proportion of participants who have positive results on blood culture tests * Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100
Time frame: Day 3, Day 5, Day 7, Day 14
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day3 | 5 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day7 | 0 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day14 | 0 Participants |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day5 | 3 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day14 | 2 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day3 | 9 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day5 | 6 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS | Day7 | 3 Participants |
Secondary
Relapse Rate of MRSA bacteremia_FAS
* Defined as a positive blood culture to MRSA when previous ones were negative * Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100
Time frame: from the first administration to TOC (4 weeks after EOT)
Population: * Participants in FAS who had MRSA negative two consecutive set in the blood culture test~* FAS (Full analysis set) : The analysis was conducted on participants who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Relapse Rate of MRSA bacteremia_FAS | 2 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Relapse Rate of MRSA bacteremia_FAS | 1 Participants |
Secondary
Relapse Rate of MRSA bacteremia_PPS
* Defined as a positive blood culture to MRSA when previous ones were negative * Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100
Time frame: from the first administration to TOC (4 weeks after EOT)
Population: * Participants in PPS who had MRSA negative two consecutive set in the blood culture test~* PPS (Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Relapse Rate of MRSA bacteremia_PPS | 2 Participants |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Relapse Rate of MRSA bacteremia_PPS | 1 Participants |
Secondary
Time to Clearance of MRSA bacteremia_FAS
If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Time frame: by EOT (up to 6 weeks)
Population: FAS (Full analysis set) : The analysis was conducted on participants who received the IP at least once after randomization and had at least one valid efficacy evaluation result. Additionally, participants who violated the inclusion/exclusion criteria were excluded from the FAS analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Time to Clearance of MRSA bacteremia_FAS | 7.00 days |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Time to Clearance of MRSA bacteremia_FAS | 8.00 days |
Secondary
Time to Clearance of MRSA bacteremia_PPS
If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Time frame: by EOT (up to 6 weeks)
Population: PPS(Per protocol set): The analysis was conducted on patients from the FAS who completed the study without experiencing major Protocol deviation and whose IP treatment compliance\* was less than 80% up to 14 days after the first dose of the IP. Participants whose reason for withdrawal is Treatment failure criteria are met during the treatment period are not excluded from the PPS.~\*(Sum of the number (tab) of actually taken up to the 14th day /14 days (minimum administration period)X4(tab))X100
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Time to Clearance of MRSA bacteremia_PPS | 4.00 days |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Time to Clearance of MRSA bacteremia_PPS | 7.00 days |
Other Pre-specified
Delpazolid MIC Levels
Delpazolid minimum inhibitory concentration (MIC) level by broth microdilution (BMD)
Time frame: Screening (Baseline), Day 14, EOT
Population: Participants in the Safety Set who were evaluated for Delpazolid MIC at baseline, Day 14, and EOT.~Of the subjects in the SS (combination: 18 subjects, monotheray: 20 subjects), Delpazolid MIC was evaluated in 18 and 17 subjects from the combination and monotherapy groups at screening, 1 and 2 at Day 14, and 1 and 0 at EOT, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Delpazolid MIC Levels | Baseline | 1.1 mcg/ml | Standard Deviation 0.34 |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Delpazolid MIC Levels | Day14 | 1.0 mcg/ml | — |
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Delpazolid MIC Levels | End of Treatment | 1.0 mcg/ml | — |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Delpazolid MIC Levels | Baseline | 1.1 mcg/ml | Standard Deviation 0.42 |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Delpazolid MIC Levels | Day14 | 1.0 mcg/ml | Standard Deviation 0 |
Other Pre-specified
Pharmacokinetics (PK) parameters_AUC,ss
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (AUC,ss: Area under the concentration-time curve at steady state)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_AUC,ss | 90,855.222 ng*h/mL |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_AUC,ss | 83,671.053 ng*h/mL |
| ESRD | Pharmacokinetics (PK) parameters_AUC,ss | 99,065.701 ng*h/mL |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_AUC,ss | 112,462.317 ng*h/mL |
| Undergoing HD | Pharmacokinetics (PK) parameters_AUC,ss | 58,444.580 ng*h/mL |
| No HI/LC | Pharmacokinetics (PK) parameters_AUC,ss | 59,842.551 ng*h/mL |
| HI/LC | Pharmacokinetics (PK) parameters_AUC,ss | 152,880.564 ng*h/mL |
Other Pre-specified
Pharmacokinetics (PK) parameters_Cmax,ss
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Cmax,ss: Maximum concentration of drug at steady state)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_Cmax,ss | 8,595.050 ng/mL | — |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_Cmax,ss | 8,610.266 ng/mL | — |
| ESRD | Pharmacokinetics (PK) parameters_Cmax,ss | 8,577.661 ng/mL | — |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_Cmax,ss | 10,903.652 ng/mL | — |
| Undergoing HD | Pharmacokinetics (PK) parameters_Cmax,ss | 5,132.147 ng/mL | Standard Deviation 938.601 |
| No HI/LC | Pharmacokinetics (PK) parameters_Cmax,ss | 6,216.075 ng/mL | — |
| HI/LC | Pharmacokinetics (PK) parameters_Cmax,ss | 13,353.002 ng/mL | — |
Other Pre-specified
Pharmacokinetics (PK) parameters_Cmin,ss
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Cmin,ss: Minimum concentration of drug at steady state)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_Cmin,ss | 6,586.689 ng/mL |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_Cmin,ss | 5,541.150 ng/mL |
| ESRD | Pharmacokinetics (PK) parameters_Cmin,ss | 7,781.590 ng/mL |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_Cmin,ss | 7,955.430 ng/mL |
| Undergoing HD | Pharmacokinetics (PK) parameters_Cmin,ss | 4,533.576 ng/mL |
| No HI/LC | Pharmacokinetics (PK) parameters_Cmin,ss | 3,992.895 ng/mL |
| HI/LC | Pharmacokinetics (PK) parameters_Cmin,ss | 11,774.277 ng/mL |
Other Pre-specified
Pharmacokinetics (PK) parameters_MRT,ss
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (MRT,ss: Mean residence time at steady state)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_MRT,ss | 6,843.719 h | — |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_MRT,ss | 1,159.389 h | — |
| ESRD | Pharmacokinetics (PK) parameters_MRT,ss | 13,340.095 h | — |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_MRT,ss | 9,730.567 h | — |
| Undergoing HD | Pharmacokinetics (PK) parameters_MRT,ss | 2,513.446 h | — |
| No HI/LC | Pharmacokinetics (PK) parameters_MRT,ss | 436.814 h | Standard Deviation 654.947 |
| HI/LC | Pharmacokinetics (PK) parameters_MRT,ss | 19,657.528 h | — |
Other Pre-specified
Pharmacokinetics (PK) parameters_t1/2β
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (t1/2β : Terminal elimination half-life)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_t1/2β | 9,292.011 h | — |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_t1/2β | 1,689.649 h | — |
| ESRD | Pharmacokinetics (PK) parameters_t1/2β | 17,980.425 h | — |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_t1/2β | 13,973.252 h | — |
| Undergoing HD | Pharmacokinetics (PK) parameters_t1/2β | 2,270.149 h | — |
| No HI/LC | Pharmacokinetics (PK) parameters_t1/2β | 425.392 h | Standard Deviation 572.107 |
| HI/LC | Pharmacokinetics (PK) parameters_t1/2β | 27,025.249 h | — |
Other Pre-specified
Pharmacokinetics (PK) parameters_Tmax,ss
Plasma LCB01-0371 concentration data in MRSA bacteremia patients were used to establish a pharmacokinetic model using NONMEM®. A two-compartment model, in which the Hemodialysis (HD) status and albumin as a covariate, was selected as the final model. (Tmax,ss: Time to reach Cmax at steady state)
Time frame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Population: Out of the total 40 enrolled patients, the blood concentrations of LCB01-0371 from the 15 patients in the treatment group who received LCB01-0371 (excluding the 19 control subjects who received placebo) were included in the population PK model analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Pharmacokinetics (PK) parameters_Tmax,ss | 3.562 h | Standard Deviation 1.322 |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Pharmacokinetics (PK) parameters_Tmax,ss | 3.083 h | Standard Deviation 1.515 |
| ESRD | Pharmacokinetics (PK) parameters_Tmax,ss | 4.110 h | Standard Deviation 0.861 |
| Not Undergoing HD | Pharmacokinetics (PK) parameters_Tmax,ss | 3.286 h | Standard Deviation 1.542 |
| Undergoing HD | Pharmacokinetics (PK) parameters_Tmax,ss | 3.978 h | Standard Deviation 0.861 |
| No HI/LC | Pharmacokinetics (PK) parameters_Tmax,ss | 3.291 h | Standard Deviation 1.429 |
| HI/LC | Pharmacokinetics (PK) parameters_Tmax,ss | 4.105 h | Standard Deviation 0.984 |
Other Pre-specified
Vancomycin MIC Level
Vancomycin minimum inhibitory concentration (MIC) levels
Time frame: at Screening visit (baseline)
Population: Participants who received the IP at least once and had samples collected for MIC evaluation among the 40 randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy - Vancomycin IV Plus Delpazolid 800 mg, PO, BID | Vancomycin MIC Level | 0.78 mcg/ml | Standard Deviation 0.256 |
| Monotherapy - Vancomycin IV Plus Placebo of Delpazolid | Vancomycin MIC Level | 0.75 mcg/ml | Standard Deviation 0.258 |