A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
Sponsor
Janssen Pharmaceutical K.K. (Industry)
Overall Status
Completed
CT.gov ID
NCT00784368
Collaborator
(none)
55
1
3
16
3.4
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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 Design
Study Type:
Interventional
Actual Enrollment
:
55 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pharmacokinetic Study of JK1211 in Patients With Systemic Fungal Infection (SFI) and Patients With Febrile Neutropenia (FN) Suspected of Fungal Infection.
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
Apr 1, 2009
Actual Study Completion Date
:
May 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: ITCZ Oral Solution
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
Other Names:
|
| Experimental: 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. |
Drug: ITCZ Oral Solution
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
Other Names:
Drug: ITCZ-IV
200 mg IV twice daily for 2 days and once daily for the next 1 to 12 days
|
| Experimental: 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. |
Drug: ITCZ Oral Solution
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
Other Names:
Drug: ITCZ-IV
200 mg IV twice daily for 2 days and once daily for the next 1 to 12 days
|
Outcome Measures
Primary Outcome Measures
- Maximum Plasma Itraconazole Concentration (Cmax) [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]) [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) [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) [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) [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) [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.
Secondary Outcome Measures
- 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)]
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).
- 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)]
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).
- 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)]
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.
- 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)]
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.
- 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)]
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).
- 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)]
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.
- 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)]
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).
- 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)]
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.
- 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)]
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).
- 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)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fukuoka | Japan |
Sponsors and Collaborators
- Janssen Pharmaceutical K.K.
Investigators
- Study Director: Janssen Pharmaceutical K.K.,Japan Clinical Trial, Janssen Pharmaceutical K.K.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT00784368
Other Study ID Numbers:
- CR014299
- JK1211-JPN-07
First Posted:
Nov 2, 2008
Last Update Posted:
Jul 25, 2013
Last Verified:
Jun 1, 2013
Keywords provided by Janssen Pharmaceutical K.K.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: Overall Study | |||
| STARTED | 16 | 16 | 23 |
| COMPLETED | 8 | 5 | 12 |
| NOT COMPLETED | 8 | 11 | 11 |
Baseline Characteristics
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 15 | 16 | 22 | 53 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
61.7
(13.6)
|
64.2
(12.0)
|
58.3
(12.7)
|
61.1
(12.8)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
6.7%
|
6
37.5%
|
7
31.8%
|
14
26.4%
|
| Male |
14
93.3%
|
10
62.5%
|
15
68.2%
|
39
73.6%
|
Outcome Measures
| Title | Maximum Plasma Itraconazole Concentration (Cmax) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 16 | 13 | 22 |
| 200 mg/day (n=11,5,12) |
2.90
(1.48)
|
2.30
(1.12)
|
1.79
(0.682)
|
| 300 mg/day (n=4,2,0) |
9.20
(2.39)
|
58.2
(NA)
|
NA
(NA)
|
| 400mg/day (n=1,6,10) |
0.948
(NA)
|
6.10
(3.12)
|
2.44
(0.996)
|
| Title | Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24]) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 16 | 13 | 22 |
| 200 mg/day (n=11,5,12) |
55.8
(34.4)
|
41.0
(25.6)
|
31.4
(14.1)
|
| 300 mg/day (n=4,2,0) |
207
(54.7)
|
129
(NA)
|
NA
(NA)
|
| 400mg/day (n=1,6,10) |
19.0
(NA)
|
137
(71.3)
|
50.4
(23.5)
|
| Title | Minimum Inhibitory Concentration (MIC) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 4 | 5 |
| 200 mg/day (n=4,1) |
0.438
(0.125)
|
0.06
(NA)
|
| 300 mg/day (n=0,1) |
NA
(NA)
|
1.00
(NA)
|
| 400mg/day (n=0,3) |
NA
(NA)
|
0.71
(0.51)
|
| Title | Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 4 | 5 |
| 200 mg/day (n=4,1) |
7.21
(2.13)
|
28.8
(NA)
|
| 300 mg/day (n=0,1) |
NA
(NA)
|
5.81
(NA)
|
| 400 mg/day (n=0,3) |
NA
(NA)
|
18.9
(21.6)
|
| Title | Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (JK1211 Monotherapy) | SFI (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with deep-seated mycosis (SFI) received JK1211 orally (taken by mouth; to be swallowed) in the dose range of 20 milliliter per day (ml/day) to 40 ml/day for 12 weeks as per Investigator's discretion. | 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. |
| Measure Participants | 4 | 5 |
| 200 mg/day (n=4,1) |
147
(56.6)
|
399
(NA)
|
| 300 mg/day (n=0,1) |
NA
(NA)
|
129
(NA)
|
| 400 mg/day (n=0,3) |
NA
(NA)
|
421
(478)
|
| Title | Time Above Minimum Inhibitory Concentration (T>MIC) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 4 | 5 |
| 200 mg/day (n=4,1) |
100
(0)
|
100
(NA)
|
| 300 mg/day (n=0,1) |
NA
(NA)
|
100
(NA)
|
| 400 mg/day (n=0,3) |
NA
(NA)
|
100
(0)
|
| Title | Number of Participants With Change in Clinical Symptoms by Centralized Assessment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) | FN (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. | 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. |
| Measure Participants | 31 | 22 |
| Disappeared |
7
46.7%
|
6
37.5%
|
| Improved |
12
80%
|
12
75%
|
| No change |
7
46.7%
|
2
12.5%
|
| Worsened |
2
13.3%
|
0
0%
|
| Could not be assessed |
3
20%
|
2
12.5%
|
| Title | Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) |
|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. |
| Measure Participants | 31 |
| Candidemia: Improved (n=1) |
1
6.7%
|
| Esophageal candidiasis: Disappeared (n=3) |
3
20%
|
| Invasive aspergillosis: Disappeared (n=5) |
2
13.3%
|
| Invasive aspergillosis: Improved (n=5) |
1
6.7%
|
| Invasive aspergillosis: Worsened (n=5) |
1
6.7%
|
| Invasive aspergillosis:Could not be assessed (n=5) |
1
6.7%
|
| C.N.P.A: Improved (n= 8) |
5
33.3%
|
| C.N.P.A: No change (n=8) |
3
20%
|
| P.A.: Improved (n=10) |
4
26.7%
|
| P.A.: No change (n=10) |
4
26.7%
|
| P.A.: Could not be assessed (n=10) |
2
13.3%
|
| P.C.: Disappeared (n=4) |
2
13.3%
|
| P.C.: Improved (n=4) |
1
6.7%
|
| P.C.: Worsened (n=4) |
1
6.7%
|
| Title | Percentage of Participants With Overall Response by Centralized Assessment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) | FN (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. | 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. |
| Measure Participants | 31 | 22 |
| E.R. |
62.1
414%
|
80.0
500%
|
| T.S.R |
58.1
387.3%
|
72.7
454.4%
|
| Title | Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment) |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) |
|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. |
| Measure Participants | 31 |
| E.R.: Candidemia (n=1) |
100.0
666.7%
|
| E.R.: Esophageal candidiasis (n=3) |
100.0
666.7%
|
| E.R.: Invasive aspergillosis (n=5) |
60.0
400%
|
| E.R.: C.N.P.A (n=8) |
62.5
416.7%
|
| E.R.: P.A. (n=10) |
50.0
333.3%
|
| E.R.: P.C. (n=4) |
50.0
333.3%
|
| T.S.R. : Candidemia (n=1) |
100.0
666.7%
|
| T.S.R. : Esophageal candidiasis (n=3) |
100.0
666.7%
|
| T.S.R. : Invasive aspergillosis (n=5) |
60.0
400%
|
| T.S.R. : C.N.P.A (n=8) |
62.5
416.7%
|
| T.S.R. : P.A. (n=10) |
40.0
266.7%
|
| T.S.R. : P.C. (n=4) |
50.0
333.3%
|
| Title | Number of Participants With Mycological Efficacy by Centralized Assessment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) | FN (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. | 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. |
| Measure Participants | 31 | 22 |
| Disappeared |
6
40%
|
0
0%
|
| No change |
1
6.7%
|
0
0%
|
| Could not be assessed |
24
160%
|
22
137.5%
|
| Title | Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) |
|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. |
| Measure Participants | 31 |
| Candidemia: Could not be assessed (n=1) |
1
6.7%
|
| Esophageal candidiasis: Disappeared (n=3) |
1
6.7%
|
| Esophageal candidiasis:Could not be assessed (n=3) |
2
13.3%
|
| Invasive aspergillosis:Could not be assessed (n=5) |
5
33.3%
|
| C.N.P.A: Disappeared (n=8) |
1
6.7%
|
| C.N.P.A: No change (n=8) |
1
6.7%
|
| C.N.P.A: Could not be assessed (n=8) |
6
40%
|
| P.A.: Disappeared (n=10) |
3
20%
|
| P.A.: Could not be assessed (n=10) |
7
46.7%
|
| P.C.: Disappeared (n=4) |
1
6.7%
|
| P.C.: Could not be assessed (n=4) |
3
20%
|
| Title | Number of Participants With Serological Effect Against Fungi by Centralized Assessment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) | FN (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. | 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. |
| Measure Participants | 31 | 22 |
| Changed to negative |
1
6.7%
|
0
0%
|
| Improved |
3
20%
|
0
0%
|
| No change |
5
33.3%
|
1
6.3%
|
| Worsened |
2
13.3%
|
2
12.5%
|
| Could not be assessed |
20
133.3%
|
19
118.8%
|
| Title | Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) |
|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. |
| Measure Participants | 31 |
| Candidemia: Changed to negative (n=1) |
1
6.7%
|
| Esophageal candidiasis:Could not be assessed (n=3) |
3
20%
|
| Invasive aspergillosis: No change (n=5) |
1
6.7%
|
| Invasive aspergillosis: Worsened (n=5) |
1
6.7%
|
| Invasive aspergillosis:Could not be assessed (n=5) |
3
20%
|
| C.N.P.A: Improved (n=8) |
2
13.3%
|
| C.N.P.A: Worsened (n=8) |
1
6.7%
|
| C.N.P.A: Could not be assessed (n=8) |
5
33.3%
|
| P.A.:No change (n=10) |
1
6.7%
|
| P.A.: Could not be assessed (n=10) |
9
60%
|
| P.C.: Improved (n=4) |
1
6.7%
|
| P.C.: No change (n=4) |
3
20%
|
| Title | Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) | FN (Switched Treatment) |
|---|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. | 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. |
| Measure Participants | 31 | 22 |
| Disappeared |
3
20%
|
0
0%
|
| Improved |
12
80%
|
0
0%
|
| No change |
7
46.7%
|
0
0%
|
| Worsened |
4
26.7%
|
1
6.3%
|
| Could not be assessed |
5
33.3%
|
21
131.3%
|
| Title | Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy + Switched Treatment) |
|---|---|
| Arm/Group Description | Participants with SFI were allocated either to SFI (ITCZ Oral Solution Monotherapy) or SFI (Switched Treatment). Participants in SFI (ITCZ Oral Solution Monotherapy) group 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. Participants in SFI (Switched Treatment) were administered 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. |
| Measure Participants | 31 |
| Candidemia: Could not be assessed (n=1) |
1
6.7%
|
| Esophageal candidiasis: Disappeared (n=3) |
3
20%
|
| Invasive aspergillosis: Improved (n=5) |
3
20%
|
| Invasive aspergillosis: Worsened (n=5) |
2
13.3%
|
| C.N.P.A: Improved (n=8) |
3
20%
|
| C.N.P.A: No change (n=8) |
3
20%
|
| C.N.P.A: Worsened (n=8) |
2
13.3%
|
| P.A.:Improved (n=10) |
3
20%
|
| P.A.:No change (n=10) |
4
26.7%
|
| P.A.: Could not be assessed (n=10) |
3
20%
|
| P.C.: Improved (n=4) |
3
20%
|
| P.C.: Could not be assessed (n=4) |
1
6.7%
|
Adverse Events
| Time Frame | Baseline up to 30 days after last dose of study drug | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/16 (25%) | 8/16 (50%) | 3/23 (13%) | |||
| Blood and lymphatic system disorders | ||||||
| Aplastic anemia | 0/16 (0%) | 0/16 (0%) | 1/23 (4.3%) | |||
| Febrile neutropenia | 0/16 (0%) | 0/16 (0%) | 1/23 (4.3%) | |||
| Cardiac disorders | ||||||
| Pericarditis | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| General disorders | ||||||
| Edema | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholestasis | 1/16 (6.3%) | 0/16 (0%) | 0/23 (0%) | |||
| Infections and infestations | ||||||
| Bronchitis | 1/16 (6.3%) | 0/16 (0%) | 0/23 (0%) | |||
| Bronchopulmonary aspergillosis | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Pneumonia | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Myelodysplastic syndrome | 0/16 (0%) | 0/16 (0%) | 1/23 (4.3%) | |||
| Nervous system disorders | ||||||
| Tremors | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Renal and urinary disorders | ||||||
| Kidney damage | 1/16 (6.3%) | 0/16 (0%) | 0/23 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Aspiration pneumonia | 0/16 (0%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Alveolar hemorrhage | 1/16 (6.3%) | 0/16 (0%) | 0/23 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| SFI (ITCZ Oral Solution Monotherapy) | SFI (Switched Treatment) | FN (Switched Treatment) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/16 (93.8%) | 16/16 (100%) | 22/23 (95.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Pancytopenia | 1/16 (6.3%) | 0/16 (0%) | 5/23 (21.7%) | |||
| Febrile neutropenia | 1/16 (6.3%) | 0/16 (0%) | 3/23 (13%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 8/16 (50%) | 10/16 (62.5%) | 6/23 (26.1%) | |||
| Nausea | 1/16 (6.3%) | 2/16 (12.5%) | 3/23 (13%) | |||
| Constipation | 2/16 (12.5%) | 0/16 (0%) | 2/23 (8.7%) | |||
| Abdominal discomfort | 2/16 (12.5%) | 1/16 (6.3%) | 0/23 (0%) | |||
| Vomiting | 1/16 (6.3%) | 1/16 (6.3%) | 1/23 (4.3%) | |||
| Abdominal distension | 0/16 (0%) | 1/16 (6.3%) | 2/23 (8.7%) | |||
| General disorders | ||||||
| Oedema | 0/16 (0%) | 3/16 (18.8%) | 3/23 (13%) | |||
| Oedema peripheral | 2/16 (12.5%) | 2/16 (12.5%) | 1/23 (4.3%) | |||
| Hepatobiliary disorders | ||||||
| Liver disorder | 5/16 (31.3%) | 4/16 (25%) | 10/23 (43.5%) | |||
| Hepatic function abnormal | 1/16 (6.3%) | 2/16 (12.5%) | 0/23 (0%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 0/16 (0%) | 3/16 (18.8%) | 1/23 (4.3%) | |||
| Investigations | ||||||
| Beta 2 microglobulin urine increased | 7/16 (43.8%) | 7/16 (43.8%) | 5/23 (21.7%) | |||
| Beta-N-acetyl-D-glucosaminidase increased | 4/16 (25%) | 2/16 (12.5%) | 5/23 (21.7%) | |||
| Alpha 1 microglobulin urine increased | 3/16 (18.8%) | 3/16 (18.8%) | 2/23 (8.7%) | |||
| Blood cholesterol decreased | 1/16 (6.3%) | 2/16 (12.5%) | 4/23 (17.4%) | |||
| C-reactive protein increased | 4/16 (25%) | 1/16 (6.3%) | 2/23 (8.7%) | |||
| Blood triglycerides increased | 1/16 (6.3%) | 0/16 (0%) | 5/23 (21.7%) | |||
| Platelet count decreased | 2/16 (12.5%) | 2/16 (12.5%) | 2/23 (8.7%) | |||
| Urine analysis abnormal | 2/16 (12.5%) | 1/16 (6.3%) | 3/23 (13%) | |||
| Blood bilirubin increased | 1/16 (6.3%) | 0/16 (0%) | 4/23 (17.4%) | |||
| Blood creatine phosphokinase increased | 2/16 (12.5%) | 3/16 (18.8%) | 0/23 (0%) | |||
| Blood glucose increased | 1/16 (6.3%) | 1/16 (6.3%) | 2/23 (8.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypokalaemia | 3/16 (18.8%) | 6/16 (37.5%) | 12/23 (52.2%) | |||
| Malnutrition | 0/16 (0%) | 1/16 (6.3%) | 8/23 (34.8%) | |||
| Decreased appetite | 2/16 (12.5%) | 1/16 (6.3%) | 3/23 (13%) | |||
| Hyperglycaemia | 0/16 (0%) | 1/16 (6.3%) | 2/23 (8.7%) | |||
| Nervous system disorders | ||||||
| Hypoaesthesia | 1/16 (6.3%) | 1/16 (6.3%) | 1/23 (4.3%) | |||
| Renal and urinary disorders | ||||||
| Renal disorder | 3/16 (18.8%) | 2/16 (12.5%) | 2/23 (8.7%) | |||
| Renal tubular disorder | 2/16 (12.5%) | 2/16 (12.5%) | 2/23 (8.7%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 2/16 (12.5%) | 2/16 (12.5%) | 3/23 (13%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/16 (0%) | 1/16 (6.3%) | 2/23 (8.7%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Director, Established Products |
|---|---|
| Organization | Global Medical Organization; Janssen R&D |
| Phone | (609) 730-7674 |
Responsible Party:
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT00784368
Other Study ID Numbers:
- CR014299
- JK1211-JPN-07
First Posted:
Nov 2, 2008
Last Update Posted:
Jul 25, 2013
Last Verified:
Jun 1, 2013