A Multicenter, Double-blinded, Randomized, Parallel Design, Phase IIa Clinical Trial to Evaluate the Efficacy, Safety and PK of LCB01-0371 With Vancomycin Versus Vancomycin Monotherapy in Patients With MRSA Bacteremia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind with placebo
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Combination therapy - Vancomycin (IV) plus Delpazolid (PO)
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: 800 mg, BID, PO
干预措施: Delpazolid (Drug)
Combination therapy - Vancomycin (IV) plus Delpazolid (PO)
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: 800 mg, BID, PO
干预措施: Vancomycin (Drug)
Monotherapy - Vancomycin (IV) plus Placebo of Delpazolid (PO)
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
干预措施: Vancomycin (Drug)
Monotherapy - Vancomycin (IV) plus Placebo of Delpazolid (PO)
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
干预措施: Placebo of Delpazolid (Drug)
结局指标
主要结局
Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS
时间窗: 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
时间窗: 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
次要结局
- Overall Cure Rate by End of Treatment (EOT)_FAS(Day 7 visit and EOT (up to 6 weeks) visit)
- Overall Cure Rate by End of Treatment (EOT)_PPS(Day 7 visit and EOT (up to 6 weeks) visit)
- Mortality From MRSA Bacteremia by EOT_FAS(During the treatment period (from the first administration to EOT (up to 6 weeks)))
- Mortality From MRSA Bacteremia by EOT_PPS(During the treatment period (from the first administration to EOT (up to 6 weeks)))
- Relapse Rate of MRSA bacteremia_FAS(from the first administration to TOC (4 weeks after EOT))
- Relapse Rate of MRSA bacteremia_PPS(from the first administration to TOC (4 weeks after EOT))
- 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))
- 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))
- Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS(Day 3, Day 5, Day 7, Day 14)
- Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS(Day 3, Day 5, Day 7, Day 14)
- Time to Clearance of MRSA bacteremia_FAS(by EOT (up to 6 weeks))
- Time to Clearance of MRSA bacteremia_PPS(by EOT (up to 6 weeks))