Trial Outcomes & Findings for A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection (NCT NCT00784368)
NCT ID: NCT00784368
Last Updated: 2013-07-25
Results Overview
The Cmax is defined as the maximum observed analyte concentration. Cmax was measured in microgram per milliliter (mcg/ml).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
55 participants
Primary outcome timeframe
Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment
Results posted on
2013-07-25
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
FN (Switched Treatment)
Participants with febrile (with fever) neutropenia (a decrease in white blood cells) (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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
16
|
16
|
23
|
|
Overall Study
COMPLETED
|
8
|
5
|
12
|
|
Overall Study
NOT COMPLETED
|
8
|
11
|
11
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
FN (Switched Treatment)
Participants with febrile (with fever) neutropenia (a decrease in white blood cells) (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.
|
|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
0
|
6
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
1
|
|
Overall Study
Adverse Event
|
6
|
9
|
2
|
|
Overall Study
Diagnosis of fever
|
0
|
0
|
1
|
|
Overall Study
Worsening of complications
|
0
|
0
|
1
|
|
Overall Study
Worsening of symptoms
|
0
|
1
|
0
|
|
Overall Study
Withdrawal of informed consent
|
0
|
1
|
0
|
Baseline Characteristics
A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
Baseline characteristics by cohort
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=15 Participants
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.
|
SFI (Switched Treatment)
n=16 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
FN (Switched Treatment)
n=22 Participants
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.
|
Total
n=53 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
61.7 years
STANDARD_DEVIATION 13.6 • n=5 Participants
|
64.2 years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
58.3 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
61.1 years
STANDARD_DEVIATION 12.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: Pharmacokinetic (PK) analysis set included all participants who received ITCZ-OS and had plasma concentration data. One participant without any infection evidence was also included in the PK population for SFI (ITCZ-OS). 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
The Cmax is defined as the maximum observed analyte concentration. Cmax was measured in microgram per milliliter (mcg/ml).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=16 Participants
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.
|
SFI (Switched Treatment)
n=13 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
FN (Switched Treatment)
n=22 Participants
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.
|
|---|---|---|---|
|
Maximum Plasma Itraconazole Concentration (Cmax)
200 mg/day (n=11,5,12)
|
2.90 mcg/ml
Standard Deviation 1.48
|
2.30 mcg/ml
Standard Deviation 1.12
|
1.79 mcg/ml
Standard Deviation 0.682
|
|
Maximum Plasma Itraconazole Concentration (Cmax)
300 mg/day (n=4,2,0)
|
9.20 mcg/ml
Standard Deviation 2.39
|
58.2 mcg/ml
Standard Deviation NA
Standard deviation obtained by sampling distribution of 2 participants was not meaningful, hence not reported.
|
NA mcg/ml
Standard Deviation NA
No participant was administered 300 mg/day dose in the FN (Switched treatment) arm.
|
|
Maximum Plasma Itraconazole Concentration (Cmax)
400mg/day (n=1,6,10)
|
0.948 mcg/ml
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
6.10 mcg/ml
Standard Deviation 3.12
|
2.44 mcg/ml
Standard Deviation 0.996
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: The PK analysis set included all participants who received ITCZ-OS and had plasma concentration data. One participant without any infection evidence was also included in the PK population, for SFI (ITCZ-OS). Here 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=16 Participants
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.
|
SFI (Switched Treatment)
n=13 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
FN (Switched Treatment)
n=22 Participants
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.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24])
200 mg/day (n=11,5,12)
|
55.8 mcg*hr per ml
Standard Deviation 34.4
|
41.0 mcg*hr per ml
Standard Deviation 25.6
|
31.4 mcg*hr per ml
Standard Deviation 14.1
|
|
Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24])
300 mg/day (n=4,2,0)
|
207 mcg*hr per ml
Standard Deviation 54.7
|
129 mcg*hr per ml
Standard Deviation NA
Standard deviation obtained by sampling distribution of 2 participants was not meaningful, hence not reported.
|
NA mcg*hr per ml
Standard Deviation NA
No participant was administered 300 mg/day dose in the FN (Switched treatment) arm.
|
|
Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24])
400mg/day (n=1,6,10)
|
19.0 mcg*hr per ml
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
137 mcg*hr per ml
Standard Deviation 71.3
|
50.4 mcg*hr per ml
Standard Deviation 23.5
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: The PK analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively. MIC was not obtained for FN (Switched treatment) and hence the data not given for the same.
The MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=4 Participants
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.
|
SFI (Switched Treatment)
n=5 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Minimum Inhibitory Concentration (MIC)
200 mg/day (n=4,1)
|
0.438 mcg per ml
Standard Deviation 0.125
|
0.06 mcg per ml
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Minimum Inhibitory Concentration (MIC)
300 mg/day (n=0,1)
|
NA mcg per ml
Standard Deviation NA
No evaluable participant was treated with 300 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
1.00 mcg per ml
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Minimum Inhibitory Concentration (MIC)
400mg/day (n=0,3)
|
NA mcg per ml
Standard Deviation NA
No evaluable participant was treated with 400 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
0.71 mcg per ml
Standard Deviation 0.51
|
—
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: The PK analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively. MIC was not obtained for FN (Switched treatment) and hence the data not given for the same.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=4 Participants
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.
|
SFI (Switched Treatment)
n=5 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC)
200 mg/day (n=4,1)
|
7.21 ratio
Standard Deviation 2.13
|
28.8 ratio
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC)
300 mg/day (n=0,1)
|
NA ratio
Standard Deviation NA
No evaluable participant was treated with 300 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
5.81 ratio
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC)
400 mg/day (n=0,3)
|
NA ratio
Standard Deviation NA
No evaluable participant was treated with 400 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
18.9 ratio
Standard Deviation 21.6
|
—
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: The PK analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively. MIC was not obtained for FN (Switched treatment) and hence the data not given for the same.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=4 Participants
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.
|
SFI (Switched Treatment)
n=5 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC)
200 mg/day (n=4,1)
|
147 hour
Standard Deviation 56.6
|
399 hour
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC)
300 mg/day (n=0,1)
|
NA hour
Standard Deviation NA
No evaluable participant was treated with 300 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
129 hour
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC)
400 mg/day (n=0,3)
|
NA hour
Standard Deviation NA
No evaluable participant was treated with 400 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
421 hour
Standard Deviation 478
|
—
|
PRIMARY outcome
Timeframe: Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatmentPopulation: The PK analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively. MIC was not obtained for FN (Switched treatment) and hence the data not given for the same.
The T\>MIC was calculated only in participants for whom the MIC was obtained.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=4 Participants
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.
|
SFI (Switched Treatment)
n=5 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Time Above Minimum Inhibitory Concentration (T>MIC)
200 mg/day (n=4,1)
|
100 percent time
Standard Deviation 0
|
100 percent time
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Time Above Minimum Inhibitory Concentration (T>MIC)
300 mg/day (n=0,1)
|
NA percent time
Standard Deviation NA
No evaluable participant was treated with 300 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
100 percent time
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
—
|
|
Time Above Minimum Inhibitory Concentration (T>MIC)
400 mg/day (n=0,3)
|
NA percent time
Standard Deviation NA
No evaluable participant was treated with 400 mg/day, so it was not possible to evaluate the relationship between the dose level and the pharmacokinetic parameters.
|
100 percent time
Standard Deviation 0
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment)Population: FAS population included all participants except those who did not meet main eligibility criteria, who did not receive ITCZ-IV or ITCZ-OS and participants without efficacy data. As per planned analysis both SFI (ITCZ Oral Solution Monotherapy) and SFI (Switched Treatment) arms were combined for all efficacy analyses.
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).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
n=22 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Change in Clinical Symptoms by Centralized Assessment
Could not be assessed
|
3 participants
|
2 participants
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Centralized Assessment
Disappeared
|
7 participants
|
6 participants
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Centralized Assessment
Improved
|
12 participants
|
12 participants
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Centralized Assessment
No change
|
7 participants
|
2 participants
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Centralized Assessment
Worsened
|
2 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)Population: The FAS population. As per planned analysis both SFI arms were combined for efficacy analyses; participants with FN with suspected fungal infection were not planned to be analyzed for this outcome measure. Here, 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Candidemia: Improved (n=1)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Esophageal candidiasis: Disappeared (n=3)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Disappeared (n=5)
|
2 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Improved (n=5)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Worsened (n=5)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis:Could not be assessed (n=5)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
C.N.P.A: Improved (n= 8)
|
5 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
C.N.P.A: No change (n=8)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.A.: Improved (n=10)
|
4 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.A.: No change (n=10)
|
4 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.A.: Could not be assessed (n=10)
|
2 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.C.: Disappeared (n=4)
|
2 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.C.: Improved (n=4)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment)
P.C.: Worsened (n=4)
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment)Population: The FAS population included all participants except those who did not meet main eligibility criteria, who did not receive ITCZ-IV or ITCZ-OS and participants without efficacy data. As per planned analysis both SFI (ITCZ Oral Solution Monotherapy) and SFI (Switched Treatment) arms were combined for all efficacy analyses.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
n=22 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Percentage of Participants With Overall Response by Centralized Assessment
E.R.
|
62.1 percentage of participants
Interval 42.3 to 79.3
|
80.0 percentage of participants
Interval 56.3 to 94.3
|
—
|
|
Percentage of Participants With Overall Response by Centralized Assessment
T.S.R
|
58.1 percentage of participants
Interval 39.1 to 75.5
|
72.7 percentage of participants
Interval 49.8 to 89.3
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)Population: The FAS population. As per planned analysis both SFI arms were combined for efficacy analyses; participants with FN with suspected fungal infection were not planned to be analyzed for this outcome measure. Here, 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: Candidemia (n=1)
|
100.0 percentage of participants
Interval 2.5 to 100.0
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: C.N.P.A (n=8)
|
62.5 percentage of participants
Interval 24.5 to 91.5
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: Esophageal candidiasis (n=3)
|
100.0 percentage of participants
Interval 29.2 to 100.0
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: Invasive aspergillosis (n=5)
|
60.0 percentage of participants
Interval 14.7 to 94.7
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: P.A. (n=10)
|
50.0 percentage of participants
Interval 15.7 to 84.3
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
E.R.: P.C. (n=4)
|
50.0 percentage of participants
Interval 6.8 to 93.2
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : Candidemia (n=1)
|
100.0 percentage of participants
Interval 2.5 to 100.0
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : Esophageal candidiasis (n=3)
|
100.0 percentage of participants
Interval 29.2 to 100.0
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : Invasive aspergillosis (n=5)
|
60.0 percentage of participants
Interval 14.7 to 94.7
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : C.N.P.A (n=8)
|
62.5 percentage of participants
Interval 24.5 to 91.5
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : P.A. (n=10)
|
40.0 percentage of participants
Interval 12.2 to 73.8
|
—
|
—
|
|
Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment)
T.S.R. : P.C. (n=4)
|
50.0 percentage of participants
Interval 6.8 to 93.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment)Population: The FAS population included all participants except those who did not meet main eligibility criteria, who did not receive ITCZ-IV or ITCZ-OS and participants without efficacy data. As per planned analysis both SFI (ITCZ Oral Solution Monotherapy) and SFI (Switched Treatment) arms were combined for all efficacy analyses.
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).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
n=22 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Mycological Efficacy by Centralized Assessment
Disappeared
|
6 participants
|
0 participants
|
—
|
|
Number of Participants With Mycological Efficacy by Centralized Assessment
No change
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Mycological Efficacy by Centralized Assessment
Could not be assessed
|
24 participants
|
22 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)Population: The FAS population. As per planned analysis both SFI arms were combined for efficacy analyses; participants with FN with suspected fungal infection were not planned to be analyzed for this outcome measure. Here, 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
Candidemia: Could not be assessed (n=1)
|
1 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
Esophageal candidiasis: Disappeared (n=3)
|
1 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
Esophageal candidiasis:Could not be assessed (n=3)
|
2 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis:Could not be assessed (n=5)
|
5 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
C.N.P.A: Disappeared (n=8)
|
1 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
C.N.P.A: No change (n=8)
|
1 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
C.N.P.A: Could not be assessed (n=8)
|
6 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
P.A.: Disappeared (n=10)
|
3 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
P.A.: Could not be assessed (n=10)
|
7 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
P.C.: Disappeared (n=4)
|
1 participants
|
—
|
—
|
|
Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment)
P.C.: Could not be assessed (n=4)
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment)Population: The FAS population included all participants except those who did not meet main eligibility criteria, who did not receive ITCZ-IV or ITCZ-OS and participants without efficacy data. As per planned analysis both SFI (ITCZ Oral Solution Monotherapy) and SFI (Switched Treatment) arms were combined for all efficacy analyses.
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).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
n=22 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Serological Effect Against Fungi by Centralized Assessment
Changed to negative
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Serological Effect Against Fungi by Centralized Assessment
Improved
|
3 participants
|
0 participants
|
—
|
|
Number of Participants With Serological Effect Against Fungi by Centralized Assessment
No change
|
5 participants
|
1 participants
|
—
|
|
Number of Participants With Serological Effect Against Fungi by Centralized Assessment
Worsened
|
2 participants
|
2 participants
|
—
|
|
Number of Participants With Serological Effect Against Fungi by Centralized Assessment
Could not be assessed
|
20 participants
|
19 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)Population: The FAS population. As per planned analysis both SFI arms were combined for efficacy analyses; participants with FN with suspected fungal infection were not planned to be analyzed for this outcome measure. Here, 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
P.A.:No change (n=10)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
Candidemia: Changed to negative (n=1)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
Esophageal candidiasis:Could not be assessed (n=3)
|
3 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: No change (n=5)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Worsened (n=5)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis:Could not be assessed (n=5)
|
3 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
C.N.P.A: Improved (n=8)
|
2 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
C.N.P.A: Worsened (n=8)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
C.N.P.A: Could not be assessed (n=8)
|
5 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
P.A.: Could not be assessed (n=10)
|
9 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
P.C.: Improved (n=4)
|
1 participants
|
—
|
—
|
|
Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment)
P.C.: No change (n=4)
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment)Population: The FAS population included all participants except those who did not meet main eligibility criteria, who did not receive ITCZ-IV or ITCZ-OS and participants without efficacy data. As per planned analysis both SFI (ITCZ Oral Solution Monotherapy) and SFI (Switched Treatment) arms were combined for all efficacy analyses.
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).
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
n=22 Participants
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment
Disappeared
|
3 participants
|
0 participants
|
—
|
|
Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment
Improved
|
12 participants
|
0 participants
|
—
|
|
Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment
No change
|
7 participants
|
0 participants
|
—
|
|
Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment
Worsened
|
4 participants
|
1 participants
|
—
|
|
Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment
Could not be assessed
|
5 participants
|
21 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment)Population: The FAS population. As per planned analysis both SFI arms were combined for efficacy analyses; participants with FN with suspected fungal infection were not planned to be analyzed for this outcome measure. Here, 'n' signifies those participants who were evaluated for this measure at specified time points for each arm group respectively.
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.
Outcome measures
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=31 Participants
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.
|
SFI (Switched Treatment)
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
C.N.P.A: Worsened (n=8)
|
2 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
P.A.:Improved (n=10)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
P.A.:No change (n=10)
|
4 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
Candidemia: Could not be assessed (n=1)
|
1 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
Esophageal candidiasis: Disappeared (n=3)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Improved (n=5)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
Invasive aspergillosis: Worsened (n=5)
|
2 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
C.N.P.A: Improved (n=8)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
C.N.P.A: No change (n=8)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
P.A.: Could not be assessed (n=10)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
P.C.: Improved (n=4)
|
3 participants
|
—
|
—
|
|
Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment)
P.C.: Could not be assessed (n=4)
|
1 participants
|
—
|
—
|
Adverse Events
SFI (ITCZ Oral Solution Monotherapy)
Serious events: 4 serious events
Other events: 15 other events
Deaths: 0 deaths
SFI (Switched Treatment)
Serious events: 8 serious events
Other events: 16 other events
Deaths: 0 deaths
FN (Switched Treatment)
Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=16 participants at risk
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.
|
SFI (Switched Treatment)
n=16 participants at risk
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
FN (Switched Treatment)
n=23 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Infections and infestations
Pneumonia
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Blood and lymphatic system disorders
Aplastic anemia
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Nervous system disorders
Tremors
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Alveolar hemorrhage
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Hepatobiliary disorders
Cholestasis
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Renal and urinary disorders
Kidney damage
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
General disorders
Edema
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
Other adverse events
| Measure |
SFI (ITCZ Oral Solution Monotherapy)
n=16 participants at risk
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.
|
SFI (Switched Treatment)
n=16 participants at risk
Participants with SFI received 200 milligram (mg) twice daily itraconazole intravenous 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.
|
FN (Switched Treatment)
n=23 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Blood and lymphatic system disorders
Pancytopenia
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
21.7%
5/23 • Baseline up to 30 days after last dose of study drug
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
37.5%
6/16 • Baseline up to 30 days after last dose of study drug
|
52.2%
12/23 • Baseline up to 30 days after last dose of study drug
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
34.8%
8/23 • Baseline up to 30 days after last dose of study drug
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Vascular disorders
Hypertension
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
8/16 • Baseline up to 30 days after last dose of study drug
|
62.5%
10/16 • Baseline up to 30 days after last dose of study drug
|
26.1%
6/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Constipation
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Abdominal discomfort
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Hepatobiliary disorders
Liver disorder
|
31.2%
5/16 • Baseline up to 30 days after last dose of study drug
|
25.0%
4/16 • Baseline up to 30 days after last dose of study drug
|
43.5%
10/23 • Baseline up to 30 days after last dose of study drug
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
Renal and urinary disorders
Renal disorder
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Renal and urinary disorders
Renal tubular disorder
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
General disorders
Oedema
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
General disorders
Oedema peripheral
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
4.3%
1/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Beta 2 microglobulin urine increased
|
43.8%
7/16 • Baseline up to 30 days after last dose of study drug
|
43.8%
7/16 • Baseline up to 30 days after last dose of study drug
|
21.7%
5/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Beta-N-acetyl-D-glucosaminidase increased
|
25.0%
4/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
21.7%
5/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Alpha 1 microglobulin urine increased
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Blood cholesterol decreased
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
17.4%
4/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
C-reactive protein increased
|
25.0%
4/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Blood triglycerides increased
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
21.7%
5/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Platelet count decreased
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Urine analysis abnormal
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
13.0%
3/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Blood bilirubin increased
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
17.4%
4/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Blood creatine phosphokinase increased
|
12.5%
2/16 • Baseline up to 30 days after last dose of study drug
|
18.8%
3/16 • Baseline up to 30 days after last dose of study drug
|
0.00%
0/23 • Baseline up to 30 days after last dose of study drug
|
|
Investigations
Blood glucose increased
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/16 • Baseline up to 30 days after last dose of study drug
|
6.2%
1/16 • Baseline up to 30 days after last dose of study drug
|
8.7%
2/23 • Baseline up to 30 days after last dose of study drug
|
Additional Information
Director, Established Products
Global Medical Organization; Janssen R&D
Phone: (609) 730-7674
Results disclosure agreements
- Principal investigator is a sponsor employee The disclosure restriction on PI is that the Sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the sponsor requires.
- Publication restrictions are in place
Restriction type: OTHER