Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00784368
Other study ID # CR014299
Secondary ID JK1211-JPN-07
Status Completed
Phase Phase 3
First received October 23, 2008
Last updated June 19, 2013
Start date January 2008
Est. completion date May 2009

Study information

Verified date June 2013
Source Janssen Pharmaceutical K.K.
Contact n/a
Is FDA regulated No
Health authority Japan: Pharmaceuticals and Medical Devices Agency
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 55
Est. completion date May 2009
Est. primary completion date April 2009
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 79 Years
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

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
ITCZ-IV
200 mg IV twice daily for 2 days and once daily for the next 1 to 12 days

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum Plasma Itraconazole Concentration (Cmax) The Cmax is defined as the maximum observed analyte concentration. Cmax was measured in microgram per milliliter (mcg/ml). Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Primary Area Under the Curve From Time Zero to 24 Hours Post-dose Observed Plasma Itraconazole Concentration (AUC[0-24]) The AUC(0-24) is area under the plasma concentration time curve from time zero (pre-dose) to 24 hours post-dose. It is usually calculated by linear trapezoidal method. AUC was measured in mcg*hour(hr) per ml. Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Primary Minimum Inhibitory Concentration (MIC) The MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation. Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Primary Maximum Plasma Drug Concentration by Minimum Inhibitory Concentration (Cmax/MIC) The Cmax is maximum observed analyte concentration and MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation. The Cmax/MIC was calculated only in participants for whom the MIC was obtained. Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Primary Area Under the Curve During 24 Hours by Minimum Inhibitory Concentration (AUC 0-24/MIC) The AUC (0-24) is defined as area under the plasma concentration-time curve over the dosing interval (24 hr). It is usually calculated by linear trapezoidal method. MIC is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after incubation. The AUC 0-24/MIC was calculated only in participants for whom the MIC was obtained. Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Primary Time Above Minimum Inhibitory Concentration (T>MIC) The T>MIC was calculated only in participants for whom the MIC was obtained. Day 85 for SFI (ITCZ Oral Solution Monotherapy); and Day 99 for SFI and FN Switched treatment No
Secondary Number of Participants With Change in Clinical Symptoms by Centralized Assessment Level of improvement in the clinical symptoms was assessed as: disappeared (if clinical symptoms disappeared), improved (significant improvement in clinical symptoms ), no change (almost no improvement in the clinical symptoms), worsened (if the clinical symptoms worsened) and could not be assessed (if it was difficult to make the above-noted assessments). Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment) No
Secondary Number of Participants With Change in Clinical Symptoms by Diagnosis Name (Centralized Assessment) Level of improvement in the clinical symptoms was assessed as: disappeared (if clinical symptoms disappeared), improved (significant improvement in clinical symptoms ), no change (almost no improvement in the clinical symptoms), worsened (if the clinical symptoms worsened) and could not be assessed (if it was difficult to make the above-noted assessments). The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, chronic necrotic pulmonary aspergillosis (C.N.P.A), pulmonary aspergilloma (P.A.) and pulmonary cryptococcosis (P.C). Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) No
Secondary Percentage of Participants With Overall Response by Centralized Assessment Efficacy rate (E.R.) was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective and cases for whom treatment was judged to be ineffective multiplied by 100. Treatment success rate (T.S.R.) was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective, cases for whom treatment was judged to be ineffective and cases for whom the efficacy could not be assessed multiplied by 100. Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment) No
Secondary Percentage of Participants With Overall Response by Diagnosis Name (Centralized Assessment) E.R. was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective and number of cases for whom treatment was judged to be ineffective multiplied by 100. T.S.R. was calculated as number of cases for whom treatment was judged to be effective divided by sum of number of cases for whom treatment was judged to be effective, number of cases for whom treatment was judged to be ineffective and number of cases for whom the efficacy could not be assessed multiplied by 100. Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) No
Secondary Number of Participants With Mycological Efficacy by Centralized Assessment Mycological efficacy was assessed as disappeared (if results for pathogenic fungus became negative, or if it was not possible to obtain the appropriate specimens), decreased (if level of pathogenic fungus was decreased in culture), no change (if there was no quantitative change in pathogenic fungus), increased (if there was a quantitative increase in pathogenic fungus, if results for pathogenic fungus became positive after start of dosing or if new pathogenic fungus was identified) , could not be assessed (if it was difficult to make the above assessment due to lack of detection in tests). Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment) No
Secondary Number of Participants With Mycological Efficacy by Diagnosis Name (Centralized Assessment) Mycological efficacy was assessed as disappeared, decreased, no change, increased, could not be assessed. The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C. Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) No
Secondary Number of Participants With Serological Effect Against Fungi by Centralized Assessment Serological effect against fungi was assessed as changed to negative (if the test values became negative), improved (if the test values decreased), no change (if there was no change in the test values), no change (if there was no change in the test values) , worsened (if the test values increased) and could not be assessed (if it was difficult to make the above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing). Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment) No
Secondary Number of Participants With Serologic Effect Against Fungi by Diagnosis Name (Centralized Assessment) Serological effect against fungi was assessed as changed to negative (if the test values became negative), improved (if the test values decreased), no change (if there was no change in the test values), worsened (if the test values increased) and could not be assessed (if it was difficult to make above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing). The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C. Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) No
Secondary Number of Participants With Change In the Endoscopy or Image Diagnosis By Centralized Assessment Level of Improvement in the Endoscopy or Image diagnosis was assessed as disappeared (if the abnormal findings were normalized), decreased (if level of pathogenic fungus was decreased in culture), improved (if significant improvement was observed in the abnormal findings), no change (if no significant improvement was observed in the abnormal findings), worsened (if the abnormal findings were worsened) and could not be assessed (if it was difficult to make the above-noted assessments due to a reason such as a lack of detection in the tests before and after dosing). Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI and FN Switched treatment) No
Secondary Number of Participants With Change in the Endoscopy or Image Diagnosis by Diagnosis Name (Centralized Assessment) Level of Improvement in Endoscopy was assessed as disappeared, decreased, improved, no change, worsened and could not be assessed. The cases evaluated were candidemia, esophageal candidiasis, invasive aspergillosis, C.N.P.A, P.A. and P.C. Baseline up to end of treatment (Day 85 for SFI [ITCZ Oral Solution Monotherapy] and Day 99 for SFI Switched treatment) No
See also
  Status Clinical Trial Phase
Completed NCT02452034 - Safety and Pharmacokinetics of Intravenous and Oral Posaconazole in Immunocompromised Children (MK-5592-097) Phase 1
Not yet recruiting NCT02806557 - Profiling Neutrophil Counts in Patients on Chemotherapy N/A
Not yet recruiting NCT01714557 - Prophylactic Piperacillin/Tazobactam in Hematopoietic Stem Cell Transplantation N/A
Completed NCT01371656 - Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation Phase 3
Active, not recruiting NCT00020865 - Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia Phase 3
Completed NCT00257790 - The Tobramycin Study Phase 4
Completed NCT00020371 - BMS-247550 in Treating Patients With Cancers That Have Not Responded to Previous Therapy Phase 1
Terminated NCT00005787 - Peripheral Stem Cell Transplantation to Prevent Neutropenia in Patients Receiving Chemotherapy for Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 1
Completed NCT00001533 - Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Cyclosporine Phase 1
Completed NCT05585463 - Safety of Acupuncture and Intracutaneous Needles in Pediatric Cancer Patients: a Retrospective Study (ACUSAFE2021)
Not yet recruiting NCT02238873 - Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma Phase 3
Completed NCT01058993 - AMD 3100 for Treatment of Myelokathexis Phase 1
Completed NCT00771810 - Study of Drug to Reduce Thrombocytopenia in Patients Receiving Chemo for Ovarian, Fallopian Tube or Peritoneal Cancer Phase 2
Completed NCT00771433 - G-CSF in Preventing Neutropenia in Women Receiving Chemotherapy for Breast Cancer Phase 2
Terminated NCT00529282 - A Study of Ceftobiprole in Patients With Fever and Neutropenia. Phase 3
Completed NCT00770172 - G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy Phase 3
Active, not recruiting NCT00030758 - Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer Phase 4
Completed NCT00001790 - Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia Phase 1
Completed NCT00002693 - Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Recurrent Acute Leukemia Phase 1
Active, not recruiting NCT04154488 - A Study of Mavorixafor in Participants With Congenital Neutropenia and Chronic Idiopathic Neutropenia Disorders Phase 1/Phase 2