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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
ITCZ syrup product containing ITCZ 10 mg per ml in dose range of 20 ml to 40 ml daily for 7 days up to 12 weeks
200 mg IV twice daily for 2 days and once daily for the next 1 to 12 days
Unnamed facility
Fukuoka, Japan
Maximum Plasma Itraconazole Concentration (Cmax)
The Cmax is defined as the maximum observed analyte concentration. Cmax was measured in microgram per milliliter (mcg/ml).
Time frame: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24])
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.
Time frame: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Minimum Inhibitory Concentration (MIC)
The MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation.
Time frame: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC)
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.
Time frame: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC)
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 frame: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Time Above Minimum Inhibitory Concentration (T>MIC)
The T\>MIC was calculated only in participants for whom the MIC was obtained.
Time frame: 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 Centralized Assessment
Level of improvement in the clinical symptoms was assessed as: disappeared (if clinical symptoms disappeared), improved (significant improvement in clinical symptoms ), no change (almost no improvement in the clinical symptoms), worsened (if the clinical symptoms worsened) and could not be assessed (if it was difficult to make the above-noted assessments).
Time frame: 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)
Level of improvement in the clinical symptoms was assessed as: disappeared (if clinical symptoms disappeared), improved (significant improvement in clinical symptoms ), no change (almost no improvement in the clinical symptoms), worsened (if the clinical symptoms worsened) and could not be assessed (if it was difficult to make the above-noted assessments). The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, chronic necrotic pulmonary aspergillosis (C.N.P.A), pulmonary aspergilloma (P.A.) and pulmonary cryptococcosis (P.C).
Time frame: 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
Efficacy rate (E.R.) was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective and cases for whom treatment was judged to be ineffective multiplied by 100. Treatment success rate (T.S.R.) was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective, cases for whom treatment was judged to be ineffective and cases for whom the efficacy could not be assessed multiplied by 100.
Time frame: 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)
E.R. was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective and number of cases for whom treatment was judged to be ineffective multiplied by 100. T.S.R. was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective, number of cases for whom treatment was judged to be ineffective and number of cases for whom the efficacy could not be assessed multiplied by 100.
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Time frame: 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
Mycological efficacy was assessed as disappeared (if results for pathogenic fungus became negative, or if it was not possible to obtain the appropriate specimens), decreased (if level of pathogenic fungus was decreased in culture), no change (if there was no quantitative change in pathogenic fungus), increased (if there was a quantitative increase in pathogenic fungus, if results for pathogenic fungus became positive after start of dosing or if new pathogenic fungus was identified) , could not be assessed (if it was difficult to make the above assessment due to lack of detection in tests).
Time frame: 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)
Mycological efficacy was assessed as disappeared, decreased, no change, increased, could not be assessed. The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C.
Time frame: 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
Serological effect against fungi was assessed as changed to negative (if the test values became negative), improved (if the test values decreased), no change (if there was no change in the test values), no change (if there was no change in the test values) , worsened (if the test values increased) and could not be assessed (if it was difficult to make the above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing).
Time frame: 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)
Serological effect against fungi was assessed as changed to negative (if the test values became negative), improved (if the test values decreased), no change (if there was no change in the test values), worsened (if the test values increased) and could not be assessed (if it was difficult to make above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing). The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C.
Time frame: 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 the Endoscopy or Image Diagnosis By Centralized Assessment
Level of Improvement in the Endoscopy or Image diagnosis was assessed as disappeared (if the abnormal findings were normalized), decreased (if level of pathogenic fungus was decreased in culture), improved (if significant improvement was observed in the abnormal findings), no change (if no significant improvement was observed in the abnormal findings), worsened (if the abnormal findings were worsened) and could not be assessed (if it was difficult to make the above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing).
Time frame: 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)
Level of Improvement in Endoscopy was assessed as disappeared, decreased, improved, no change, worsened and could not be assessed. The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C.
Time frame: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)