Trial Outcomes & Findings for The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants (NCT NCT01021683)
NCT ID: NCT01021683
Last Updated: 2013-08-12
Results Overview
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).
COMPLETED
203 participants
Day 5
2013-08-12
Participant Flow
Participant milestones
| Measure |
Itraconazole
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 Study
STARTED
|
203
|
|
Overall Study
COMPLETED
|
132
|
|
Overall Study
NOT COMPLETED
|
71
|
Reasons for withdrawal
| Measure |
Itraconazole
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 Study
Lack of Efficacy
|
12
|
|
Overall Study
Recovery of neutrophil count
|
51
|
|
Overall Study
Other
|
8
|
Baseline Characteristics
The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants
Baseline characteristics by cohort
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Age Continuous
|
52.2 Years
STANDARD_DEVIATION 15.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
65 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 5Population: 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.
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).
Outcome measures
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment
|
68.0 Percentage of Participants
Interval 60.53 to 75.5
|
SECONDARY outcome
Timeframe: Day 0 up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Percentage of Participants With Deferevescence After Administration of Study Treatment
|
87.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 0 up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=131 Participants
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.
|
|---|---|
|
Mean Time to Defervescence in Participants Who Received the Study Treatment
|
3.14 Days
Standard Deviation 1.57 • Interval 2.0 to 13.0
|
SECONDARY outcome
Timeframe: Day 0 up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Duration of Neutropenia
|
2.64 Days
Standard Deviation 1.96
|
SECONDARY outcome
Timeframe: Baseline (Day 0)Population: 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.
The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.
Outcome measures
| Measure |
Itraconazole
n=148 Participants
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.
|
|---|---|
|
Absolute Neutrophil Count (ANC)
|
56.26 Cells/mm^3
Standard Deviation 127.91
|
SECONDARY outcome
Timeframe: Day 5Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Percentage of Participants With Defervescence by Plasma Level of Itraconazole
IC+HIC < 1000ng/mL (n=48)
|
70.8 Percentage of Participants
|
|
Percentage of Participants With Defervescence by Plasma Level of Itraconazole
IC+HIC >= 1000ng/mL (n=102)
|
95.1 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 5Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=134 Participants
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.
|
|---|---|
|
Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment
Presence of OS (n=95)
|
2328.10 ng/mL
Standard Deviation 1612.00
|
|
Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment
Absence of OS (n=39)
|
1690.90 ng/mL
Standard Deviation 1185.20
|
SECONDARY outcome
Timeframe: Baseline (Day 0)Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=150 Participants
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.
|
|---|---|
|
Percentage of Participants With Baseline Fungal Infection
|
5.3 Percentage of Participants
1185.20
|
SECONDARY outcome
Timeframe: Day 5Population: 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.
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.
Outcome measures
| Measure |
Itraconazole
n=134 Participants
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.
|
|---|---|
|
Plasma Concentration of Itraconazole by Breakthrough Fungal Infection
Presence of Breakthrough Fungal infection (n=128)
|
2155.70 ng/mL
Standard Deviation 1529.20
|
|
Plasma Concentration of Itraconazole by Breakthrough Fungal Infection
Absence of Breakthrough Fungal infection (n=6)
|
1864.20 ng/mL
Standard Deviation 1509.80
|
Adverse Events
Itraconazole
Serious adverse events
| Measure |
Itraconazole
n=203 participants at risk
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.
|
|---|---|
|
Infections and infestations
Bacterial sepsis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Cardiac disorders
Cardiac arrest
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Disease progression
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Vascular disorders
Embolism
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Hematemesis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Lung abscess
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Multi-organ failure
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Neutropenic sepsis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Pneumonia
|
3.0%
6/203 • Day 1 up to Day 14
|
|
Renal and urinary disorders
Pneumonia aspiration
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Renal and urinary disorders
Renal failure acute
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Infections and infestations
Sepsis
|
3.0%
6/203 • Day 1 up to Day 14
|
|
Infections and infestations
Septic shock
|
2.5%
5/203 • Day 1 up to Day 14
|
Other adverse events
| Measure |
Itraconazole
n=203 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.9%
8/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Abdominal distension
|
1.5%
3/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Nausea
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Abdominal pain
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Anal ulcer
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Constipation
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Dyspepsia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Haematochezia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Hemorroids
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Lip disorder
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Stomatitis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Gastrointestinal disorders
Vomiting
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Aspartate aminotransferase increased
|
2.5%
5/203 • Day 1 up to Day 14
|
|
Investigations
Alanine aminotransferase increased
|
2.0%
4/203 • Day 1 up to Day 14
|
|
Investigations
Blood alkaline phosphatase increased
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Investigations
Blood bilirubin increased
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Haemoglobin decreased
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Hepatic enzymes increased
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Liver function test abnormal
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Investigations
Transaminases increased
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Pneumonia
|
1.5%
3/203 • Day 1 up to Day 14
|
|
Infections and infestations
Bronchopneumonia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
H1N1 influenza
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Lung abscess
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Sepsis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Sinusitis
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Infections and infestations
Streptococcal infection
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.5%
5/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Oedema peripheral
|
0.99%
2/203 • Day 1 up to Day 14
|
|
General disorders
Asthenia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Oedema
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Pain
|
0.49%
1/203 • Day 1 up to Day 14
|
|
General disorders
Pyrexia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Nervous system disorders
Headache
|
1.5%
3/203 • Day 1 up to Day 14
|
|
Nervous system disorders
Depressed level of consciousness
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Nervous system disorders
Hypoaesthesia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
2.0%
4/203 • Day 1 up to Day 14
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Cardiac disorders
Arrhythmia
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Cardiac disorders
Tachycardia
|
0.99%
2/203 • Day 1 up to Day 14
|
|
Cardiac disorders
Atrial fibrillation
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Psychiatric disorders
Disorientation
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Renal and urinary disorders
Anuria
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.49%
1/203 • Day 1 up to Day 14
|
|
Vascular disorders
Hypotension
|
0.49%
1/203 • Day 1 up to Day 14
|
Additional Information
Clinical Research Associate
Clinical Research Team, Medical Affairs, Medical Dept. Janssen Korea
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER