A Pharmacokinetic Study of JK1211 in Patients With Systemic Fungal Infection (SFI) and Patients With Febrile Neutropenia (FN) Suspected of Fungal Infection.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 55
- 主要终点
- Maximum Plasma Itraconazole Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics (how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time) of itraconazole (ITCZ) oral solution in participants with Systemic Fungal Infection (SFI) and those with febrile (with fever) neutropenia (FN, decrease in white blood cells) suspected of fungal infection.
详细描述
This is an open-label (all people know the identity of the intervention), multicenter (conducted in more than 1 center) and uncontrolled (no competitive drugs involved) study. Participants with SFI will receive treatment with ITCZ oral solution or switch treatment from intravenous (into a vein) infusion of itraconazole (ITCZ-intravenous) to ITCZ oral solution as per Investigator's discretion. All the participants with FN suspected of fungal infection will receive the switch treatment from ITCZ- intravenous to ITCZ oral solution. The study will include 3 periods: Pre-observation period (7 days), Treatment period (85 days for ITCZ oral solution monotherapy and 99 days for switch treatment) and Follow-up observation period (30 days). The participants who receive ITCZ oral solution monotherapy will receive ITCZ oral solution without ITCZ-intravenous in the dose range of 20 milliliter (ml) per day to 40 ml per day for 12 weeks (85 days) and those on the switch treatment will receive 400 milligram (mg) per day ITCZ-intravenous twice for first 2 days followed by 200 mg per day ITCZ-intravenous up to 14 days and then they will be administered treatment as per ITCZ oral solution monotherapy. Efficacy will primarily be evaluated by assessing the pharmacokinetics. Participants' safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In case of participants with deep-seated mycosis (systemic fungal infection [SFI]) they should be either clinically suspected case or proven case
- •All participants administered need to be hospitalized during the itraconazole intravenous treatment
- •For participants with febrile (with fever) neutropenia (a decrease in white blood cells) suspected of fungal infection who have persistent fever (greater than equal to 37.5 degree celsius; greater than equal to 3 days) and have neutrophil count less than 500 per cubic millimeter (or less than 1000 per cubic millimeter and expected to decrease toward less than 500 per cubic millimeter
排除标准
- •No past history of hypersensitivity to azole antifungal agents
- •No current medication with antifungal agents such as amphotericin B (intravenous injection [injection of a substance into a vein], tablets, syrup), nystatin (tablets), fluconazole (capsules, intravenous injection), flucytosine (oral agent), miconazole (intravenous injection, gel), micafungin (intravenous infusion), fosfluconazole (intravenous injection,) voriconazole (intravenous injection, tablets), liposomal amphotericin B (intravenous injection), posaconazole
- •No medication with itraconazole in any formulation within the last 28 days
- •Participants with history of severe hepatic disease (except hepatic dysfunction because of fungal infection) and congestive heart failure
- •Female participants who are either pregnant, nursing, suspected to be pregnant or will become pregnant during the trial duration
研究组 & 干预措施
SFI (ITCZ Oral Solution Monotherapy)
Participants with deep-seated mycosis (Systemic Fungal Infection [SFI]) received itraconazole (ITCZ) oral solution in the dose range of 20 milliliter (ml) per day to 40 ml per day for 12 weeks as per Investigator's discretion.
干预措施: ITCZ Oral Solution (Drug)
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous (into the vein) infusion (ITCZ-IV) for first 2 days followed by 200 mg per day ITCZ-IV up to 14 days. Participants then received ITCZ oral solution in the dose range of 20 ml per day to 40 ml per day for 12 weeks as per Investigator's discretion.
干预措施: ITCZ Oral Solution (Drug)
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous (into the vein) infusion (ITCZ-IV) for first 2 days followed by 200 mg per day ITCZ-IV up to 14 days. Participants then received ITCZ oral solution in the dose range of 20 ml per day to 40 ml per day for 12 weeks as per Investigator's discretion.
干预措施: ITCZ-IV (Drug)
FN (Switched treatment)
Participants with febrile neutropenia (FN) with suspected fungal infection received 200 mg twice daily ITCZ-IV for first 2 days followed by 200 mg per day ITCZ-IV up to 14 days. Participants then received ITCZ oral solution in the dose range of 20 ml per day to 40 ml per day for 12 weeks as per Investigator's discretion.
干预措施: ITCZ Oral Solution (Drug)
FN (Switched treatment)
Participants with febrile neutropenia (FN) with suspected fungal infection received 200 mg twice daily ITCZ-IV for first 2 days followed by 200 mg per day ITCZ-IV up to 14 days. Participants then received ITCZ oral solution in the dose range of 20 ml per day to 40 ml per day for 12 weeks as per Investigator's discretion.
干预措施: ITCZ-IV (Drug)
结局指标
主要结局
Maximum Plasma Itraconazole Concentration (Cmax)
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The Cmax is defined as the maximum observed analyte concentration. Cmax was measured in microgram per milliliter (mcg/ml).
Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24])
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The AUC(0-24) is area under the plasma concentration time curve from time zero (pre-dose) to 24 hours post-dose. It is usually calculated by linear trapezoidal method. AUC was measured in mcg\*hour(hr) per ml.
Minimum Inhibitory Concentration (MIC)
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation.
Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC)
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The Cmax is maximum observed analyte concentration and MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation. The Cmax/MIC was calculated only in participants for whom the MIC was obtained.
Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC)
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The AUC (0-24) is defined as area under the plasma concentration-time curve over the dosing interval (24 hr). It is usually calculated by linear trapezoidal method. MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation. The AUC 0-24/MIC was calculated only in participants for whom the MIC was obtained.
Time Above Minimum Inhibitory Concentration (T>MIC)
时间窗: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
The T\>MIC was calculated only in participants for whom the MIC was obtained.
次要结局
- Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment))
- Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment))
- Number of Participants With Change in Clinical Symptoms by Centralized Assessment(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment))
- Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment))
- Percentage of Participants With Overall Response by Centralized Assessment(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment))
- Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment))
- Number of Participants With Mycological Efficacy by Centralized Assessment(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment))
- Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment))
- Number of Participants With Serological Effect Against Fungi by Centralized Assessment(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment))
- Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)(Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment))