A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, Tolerability, and Efficacy of Intravenous CD101 vs Intravenous Caspofungin Followed by Oral Fluconazole Step-down in the Treatment of Subjects With Candidemia and/or Invasive Candidiasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 63
- 主要终点
- Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
The purpose of this study is to determine if intravenous CD101 is safe and effective in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by oral fluconazole).
详细描述
This Bridging Extension is to determine if intravenous CD101 is safe [Day 45- 52 for subjects with candidemia only, or Day 52- 59 for subjects with invasive candidiasis with or without candidemia] and effective [Day 14 (± 1 day)] in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by oral fluconazole).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken less than or equal to 96 hours before randomization (defined as: at least 1 blood culture positive for Candida or positive test for Candida from a sponsor approved rapid diagnostic test or positive gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site)
- •willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required. Patients receiving only medications and measures for comfort and not cure should not be enrolled.
- •female subjects of child bearing potential <2 years post menopausal must agree to one barrier method and one highly effective method of birth control or sexual abstinence.
- •male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm from first dose of CD101 (Day 1) until 90 days following last administration of study drug.
- •willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally acceptable representative must provide informed consent on their behalf.
- •presence of one or more systemic signs attributable to candidemia and/or invasive candidiasis
排除标准
- •Any of the following forms of IC:
- •Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)
- •Osteomyelitis
- •Endocarditis or myocarditis
- •Meningitis, endophthalmitis, or any central nervous system infection
- •neutropenia
- •alanine aminotransferase or aspartate aminotransferase levels >10 fold the upper limit of normal
- •severe hepatic impairment in subjects with a history of chronic cirrhosis
- •greater than 48 hours systemic antifungal treatment at approved doses to treat candidemia
- •pregnant females
- •lactating females who are nursing
- •known hypersensitivity to CD101, caspofungin, any echinocandin, or to any of their excipients
- •previous participation in this or any previous CD101 study
- •recent use of an investigational medicinal product within 28 days of first dose of study drug or presence of an investigational device at the time of screening
- •Principal Investigator considers the subject should not participate
- •presence of indwelling vascular catheter or device that cannot be removed and is likely to be the source of candidemia
研究组 & 干预措施
Group 1
Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: CD101 (Drug)
Group 1
Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: intravenous placebo (Drug)
Group 1
Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: oral placebo (Drug)
Group 3
Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).
After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.
干预措施: Caspofungin (Drug)
Group 3
Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).
After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.
干预措施: Fluconazole (Drug)
Group 3
Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).
After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.
干预措施: intravenous placebo (Drug)
Group 2
Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: CD101 (Drug)
Group 2
Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: intravenous placebo (Drug)
Group 2
Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.
Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.
干预措施: oral placebo (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
时间窗: From first dose of study drug through Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.
Number of Subjects with Incidence of Treatment Emergent Adverse Events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.
Resolution of Systemic Signs Attributable to Candidemia and/or Invasive Candidiasis and Mycological Eradication [Overall Success]
时间窗: Day 14 (± 1 day)
Number of subjects with mycological eradication and complete resolution of all systemic signs of candidemia and/or invasive candidiasis which were present at baseline
次要结局
- Clinical Cure(Day 14 (±1 day) and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).)
- Evaluate PK (Cmax)(Day 1, 10 minutes before end of infusion (EOI))
- Mycological Eradication and Resolution of Systemic Signs(Day 5, and Follow-up (FU Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.)
- Evaluate PK (Cmin)(Day 15, predose)
- Mycological Eradication(Day 5, Day 14 (±1 day), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia))