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The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants

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ClinicalTrials.gov Identifier: NCT01021683
Recruitment Status : Completed
First Posted : November 30, 2009
Results First Posted : July 3, 2013
Last Update Posted : August 12, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea

Study Type Observational
Study Design Observational Model: Case-Only;   Time Perspective: Prospective
Conditions Hematologic Neoplasms
Neutropenia
Fever
Intervention Drug: Itraconazole
Enrollment 203
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Itraconazole
Hide Arm/Group Description Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Period Title: Overall Study
Started 203
Completed 132
Not Completed 71
Reason Not Completed
Lack of Efficacy             12
Recovery of neutrophil count             51
Other             8
Arm/Group Title Itraconazole
Hide Arm/Group Description Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Baseline Participants 150
Hide Baseline Analysis Population Description
Baseline characteristics were reported only for intent-to-treat (ITT) population which included 150 participants.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 150 participants
52.2  (15.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants
Female
65
  43.3%
Male
85
  56.7%
1.Primary Outcome
Title Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment
Hide Description Percentage of participants who achieved more than or equal to 1000 ng/ml level after administration of study treatment were reported. Plasma level of itraconazole was defined as the sum of itraconazole concentration (IC) and hydroxyitraconazole concentration (HIC).
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 150
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
68.0
(60.53 to 75.5)
2.Secondary Outcome
Title Percentage of Participants With Deferevescence After Administration of Study Treatment
Hide Description Defervescence was defined as fall of the body temperature below 38.0 degree Celsius (C) at least once after starting to receive the study treatment.
Time Frame Day 0 up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 150
Measure Type: Number
Unit of Measure: Percentage of Participants
87.3
3.Secondary Outcome
Title Mean Time to Defervescence in Participants Who Received the Study Treatment
Hide Description The mean time to defervescence was reported in participants who received the study treatment. Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment.
Time Frame Day 0 up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 131
Mean (Standard Deviation)
Unit of Measure: Days
3.14  (1.57)
4.Secondary Outcome
Title Duration of Neutropenia
Hide Description The duration of neutropenia was reported. Neutropenia was defined as neutrophil count less than or equal to (<=) 500 cells per cubic millimeter (cells/mm^3), or neutrophil count <=1000 cells/mm^3 and anticipated to decrease to <=500 cells/mm^3 within several days.
Time Frame Day 0 up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 150
Mean (Standard Deviation)
Unit of Measure: Days
2.64  (1.96)
5.Secondary Outcome
Title Absolute Neutrophil Count (ANC)
Hide Description The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.
Time Frame Baseline (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 148
Mean (Standard Deviation)
Unit of Measure: Cells/mm^3
56.26  (127.91)
6.Secondary Outcome
Title Percentage of Participants With Defervescence by Plasma Level of Itraconazole
Hide Description Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment. Plasma level of itraconazole was defined as the sum of IC and HIC.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'n' signifies participants who were evaluable for this measure at given time points.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 150
Measure Type: Number
Unit of Measure: Percentage of Participants
IC+HIC < 1000ng/mL (n=48) 70.8
IC+HIC >= 1000ng/mL (n=102) 95.1
7.Secondary Outcome
Title Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment
Hide Description Plasma level of itraconazole was defined as the sum of IC and HIC. The OSR was defined based on satisfaction of the following criteria: (1) participants if treated for baseline fungal infection, there was either eradication (removal of fungus in culture), or presumed eradication; no evidence in culture but appeared to be treated clinically, (2) absence of breakthrough fungal infection during the treatment and for 7 days after completing the treatment, (3) survival for 7 days after completing the treatment, (4) absence of early withdrawal due to adverse events or lack of efficacy, and (5) defervescence. The presence and absence of OS was reported.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for given category.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 134
Mean (Standard Deviation)
Unit of Measure: ng/mL
Presence of OS (n=95) 2328.10  (1612.00)
Absence of OS (n=39) 1690.90  (1185.20)
8.Secondary Outcome
Title Percentage of Participants With Baseline Fungal Infection
Hide Description Blood cultures (a laboratory test on a sample of blood) were assessed to identify fungus. Percentage of participants with presence or absence of fungus before starting the study drug were calculated.
Time Frame Baseline (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 150
Measure Type: Number
Unit of Measure: Percentage of Participants
5.3
9.Secondary Outcome
Title Plasma Concentration of Itraconazole by Breakthrough Fungal Infection
Hide Description Plasma level of itraconazole was defined as the sum of IC and HIC. A breakthrough fungal infection was defined as any fungal infection that was diagnosed more than (>) 3 days on or during therapy or within 7 days after completion of therapy. Blood cultures were assessed to identify fungus.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for given category.
Arm/Group Title Itraconazole
Hide Arm/Group Description:
Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Number of Participants Analyzed 134
Mean (Standard Deviation)
Unit of Measure: ng/mL
Presence of Breakthrough Fungal infection (n=128) 2155.70  (1529.20)
Absence of Breakthrough Fungal infection (n=6) 1864.20  (1509.80)
Time Frame Day 1 up to Day 14
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Itraconazole
Hide Arm/Group Description Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
All-Cause Mortality
Itraconazole
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Itraconazole
Affected / at Risk (%)
Total   28/203 (13.79%) 
Cardiac disorders   
Cardiac arrest * 1  1/203 (0.49%) 
Gastrointestinal disorders   
Gastrointestinal haemorrhage * 1  1/203 (0.49%) 
Hematemesis * 1  1/203 (0.49%) 
General disorders   
Disease progression * 1  1/203 (0.49%) 
Multi-organ failure * 1  1/203 (0.49%) 
Infections and infestations   
Bacterial sepsis * 1  1/203 (0.49%) 
Lung abscess * 1  1/203 (0.49%) 
Neutropenic sepsis * 1  1/203 (0.49%) 
Pneumonia * 1  6/203 (2.96%) 
Sepsis * 1  6/203 (2.96%) 
Septic shock * 1  5/203 (2.46%) 
Renal and urinary disorders   
Pneumonia aspiration * 1  1/203 (0.49%) 
Renal failure acute * 1  2/203 (0.99%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  1/203 (0.49%) 
Pulmonary edema * 1  1/203 (0.49%) 
Vascular disorders   
Embolism * 1  1/203 (0.49%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Itraconazole
Affected / at Risk (%)
Total   49/203 (24.14%) 
Blood and lymphatic system disorders   
Thrombocytopenia * 1  1/203 (0.49%) 
Neutropenia * 1  1/203 (0.49%) 
Cardiac disorders   
Arrhythmia * 1  2/203 (0.99%) 
Tachycardia * 1  2/203 (0.99%) 
Atrial fibrillation * 1  1/203 (0.49%) 
Gastrointestinal disorders   
Diarrhoea * 1  8/203 (3.94%) 
Abdominal distension * 1  3/203 (1.48%) 
Nausea * 1  2/203 (0.99%) 
Abdominal pain * 1  1/203 (0.49%) 
Anal ulcer * 1  1/203 (0.49%) 
Constipation * 1  1/203 (0.49%) 
Dyspepsia * 1  1/203 (0.49%) 
Haematochezia * 1  1/203 (0.49%) 
Hemorroids * 1  1/203 (0.49%) 
Lip disorder * 1  1/203 (0.49%) 
Mouth ulceration * 1  1/203 (0.49%) 
Stomatitis * 1  1/203 (0.49%) 
Vomiting * 1  1/203 (0.49%) 
General disorders   
Oedema peripheral * 1  2/203 (0.99%) 
Asthenia * 1  1/203 (0.49%) 
Oedema * 1  1/203 (0.49%) 
Pain * 1  1/203 (0.49%) 
Pyrexia * 1  1/203 (0.49%) 
Hepatobiliary disorders   
Hyperbilirubinemia * 1  4/203 (1.97%) 
Infections and infestations   
Pneumonia * 1  3/203 (1.48%) 
Bronchopneumonia * 1  1/203 (0.49%) 
H1N1 influenza * 1  1/203 (0.49%) 
Lung abscess * 1  1/203 (0.49%) 
Sepsis * 1  1/203 (0.49%) 
Sinusitis * 1  1/203 (0.49%) 
Streptococcal infection * 1  1/203 (0.49%) 
Investigations   
Aspartate aminotransferase increased * 1  5/203 (2.46%) 
Alanine aminotransferase increased * 1  4/203 (1.97%) 
Blood alkaline phosphatase increased * 1  2/203 (0.99%) 
Blood bilirubin increased * 1  1/203 (0.49%) 
Blood lactate dehydrogenase increased * 1  1/203 (0.49%) 
Haemoglobin decreased * 1  1/203 (0.49%) 
Hepatic enzymes increased * 1  1/203 (0.49%) 
Liver function test abnormal * 1  1/203 (0.49%) 
Transaminases increased * 1  1/203 (0.49%) 
Metabolism and nutrition disorders   
Hypokalaemia * 1  2/203 (0.99%) 
Decreased appetite * 1  1/203 (0.49%) 
Hyperkalaemia * 1  1/203 (0.49%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  1/203 (0.49%) 
Back pain * 1  1/203 (0.49%) 
Flank pain * 1  1/203 (0.49%) 
Nervous system disorders   
Headache * 1  3/203 (1.48%) 
Depressed level of consciousness * 1  1/203 (0.49%) 
Hypoaesthesia * 1  1/203 (0.49%) 
Psychiatric disorders   
Disorientation * 1  1/203 (0.49%) 
Renal and urinary disorders   
Anuria * 1  1/203 (0.49%) 
Reproductive system and breast disorders   
Vaginal haemorrhage * 1  1/203 (0.49%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  5/203 (2.46%) 
Epistaxis * 1  2/203 (0.99%) 
Acute respiratory distress syndrome * 1  1/203 (0.49%) 
Cough * 1  1/203 (0.49%) 
Productive cough * 1  1/203 (0.49%) 
Skin and subcutaneous tissue disorders   
Rash * 1  2/203 (0.99%) 
Decubitus ulcer * 1  1/203 (0.49%) 
Erythema * 1  1/203 (0.49%) 
Pruritus * 1  1/203 (0.49%) 
Rash pruritic * 1  1/203 (0.49%) 
Vascular disorders   
Hypotension * 1  1/203 (0.49%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI cannot provide any trial related information to external parties without mutual agreement with the Sponsor. This is valid even after the contract is cancelled.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Research Associate
Organization: Clinical Research Team, Medical Affairs, Medical Dept. Janssen Korea
Phone: +82-2-2094-4879
Layout table for additonal information
Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01021683     History of Changes
Other Study ID Numbers: CR016597
ITR-KOR-5085
ITRFUN4049
First Submitted: November 25, 2009
First Posted: November 30, 2009
Results First Submitted: April 15, 2013
Results First Posted: July 3, 2013
Last Update Posted: August 12, 2013