Pulmonary Fungal Infection
Conditions
Keywords
Invasive Pulmonary Fungal Infection, Itraconazole
Brief summary
The purpose of this study is to evaluate the efficacy and safety of itraconazole sequential therapy (intravenous injection/oral solution) in participants with invasive pulmonary fungal infections (\[IPFI\]; lung diseases caused by fungal infection).
Detailed description
This is an open-label (all people know the identity of the intervention), single arm, multicenter (when more than one hospital or medical school team work on a medical research study) study to evaluate the efficacy and safety of itraconazole sequential therapy in participants with IPFI. The study duration will be 4 to 6 weeks. The treatment will be divided into the intravenous (into a vein) injection period and the oral solution administration (giving) period. During the intravenous injection period 200 milligram (mg) twice daily loading dose (large initial dose) will be given for first 2 days, 200 mg once daily for the subsequent 12 days. Then sequential itraconazole oral solution 200 mg twice daily will be given as maintenance therapy (treatment designed to help the original primary treatment to succeed) for 2-4 weeks. Participant's clinical, mycological and comprehensive efficacy will be assessed at Week 6. Participants' safety will be monitored throughout the study.
Interventions
DRUGItraconazole
Itraconazole 200 milligram (mg) intravenous injection will be given twice daily for first 2 days, 200 mg once daily for the subsequent 12 days, then sequential itraconazole oral solution 200 mg twice daily will be given for 2 to 4 weeks.
Sponsors
Xian-Janssen Pharmaceutical Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Probable or proven invasive pulmonary infectious participants (IPFI) - Hospitalized participants (at least hospitalized treatment and observation could be ensured during the intravenous injection period) - The participants (or legal representatives) have signed the informed consent forms.
Exclusion criteria
* Currently taking taboo drugs, such as terfenadine, astemizole, cisapride and HMG CoA reductase inhibitors (for example simvastatin, lovastatin, oral or intravenous midazolam or triazolam) - History of allergy or intolerance to imidazoles or pyrrole drugs (for example fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole) - Pregnant and breast feeding women, or women of child bearing age not taking effective contraception measures - Participants with pure oral, urinary tract, and vaginal candidiasis (yeast infection) - Participants with fungal meningitis (inflammation of the meninges), active liver disease, renal insufficiency with the serum creatinine clearance rate less than 30 milliliter per minute (ml/min), and current abnormal cardiac function such as congestive heart failure (condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body), or participants with history of congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Efficacy | Week 6 | Clinical efficacy was assessed as cured: the signs and symptoms of invasive fungal infections (IFI) completely disappeared or full or nearby resolution of radiographic manifestations; markedly improved: the signs and symptoms of IFI were improved or disappeared and at least 50 percent improvement of radiographic findings; improved: the signs and symptoms of IFI were moderately improved and less than 50 percent improvement of radiographic findings; failed: the clinical symptoms and signs of IFI were not changed or worsened. |
| Number of Participants With Mycological Efficacy | Week 6 | Mycological efficacy was assessed as fungi cleared: negative for fungal microscopic examination and culture (test for infection or organisms that could cause infection); fungi not cleared: positive for fungal microscopic examinations and/or culture. |
| Number of Participants With Comprehensive Efficacy | Week 6 | Comprehensive efficacy was assessed as cured: the symptoms, signs, laboratory examination and pathogenic examination were return to normal; markedly improved: the disease condition was markedly improved but symptoms, signs, laboratory examination and pathogenic examination were not return to normal; improved: the disease condition was improved to some extent after drug administration, but the improvement was not significant enough; failed: the disease condition was not improved significantly or worsened after drug administration. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Itraconazole Sequential Therapy Itraconazole 200 milligram (mg) intravenous (directly into the vein) injection was given twice daily for first 2 days and once daily for the subsequent 12 days, then sequential itraconazole oral solution 200 mg twice daily was given for 2 to 4 weeks. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administered contraindicated medicine | 1 |
| Overall Study | Adverse Event | 5 |
| Overall Study | Creatinine clearance<30milliliter/minute | 1 |
| Overall Study | Drug affected efficacy and safety | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Physician Decision | 9 |
| Overall Study | Transaminase increased more than 3 times | 1 |
Baseline characteristics
| Characteristic | Itraconazole Sequential Therapy |
|---|---|
| Age Continuous | 55.5 years |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 61 |
| serious Total, serious adverse events | 4 / 61 |
Outcome results
Primary
Number of Participants With Clinical Efficacy
Clinical efficacy was assessed as cured: the signs and symptoms of invasive fungal infections (IFI) completely disappeared or full or nearby resolution of radiographic manifestations; markedly improved: the signs and symptoms of IFI were improved or disappeared and at least 50 percent improvement of radiographic findings; improved: the signs and symptoms of IFI were moderately improved and less than 50 percent improvement of radiographic findings; failed: the clinical symptoms and signs of IFI were not changed or worsened.
Time frame: Week 6
Population: The Full analysis set (FAS) population included all participants who received at least 1 intravenous infusion or oral solution of the study drug and completed at least 1 post-baseline visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Itraconazole Sequential Therapy | Number of Participants With Clinical Efficacy | Cured | 8 participants |
| Itraconazole Sequential Therapy | Number of Participants With Clinical Efficacy | Markedly Improved | 29 participants |
| Itraconazole Sequential Therapy | Number of Participants With Clinical Efficacy | Improved | 18 participants |
| Itraconazole Sequential Therapy | Number of Participants With Clinical Efficacy | Failed | 5 participants |
Primary
Number of Participants With Comprehensive Efficacy
Comprehensive efficacy was assessed as cured: the symptoms, signs, laboratory examination and pathogenic examination were return to normal; markedly improved: the disease condition was markedly improved but symptoms, signs, laboratory examination and pathogenic examination were not return to normal; improved: the disease condition was improved to some extent after drug administration, but the improvement was not significant enough; failed: the disease condition was not improved significantly or worsened after drug administration.
Time frame: Week 6
Population: The Full analysis set (FAS) population included all participants who received at least 1 intravenous infusion or oral solution of the study drug and completed at least 1 post-baseline visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Itraconazole Sequential Therapy | Number of Participants With Comprehensive Efficacy | Cured | 8 participants |
| Itraconazole Sequential Therapy | Number of Participants With Comprehensive Efficacy | Markedly Improved | 32 participants |
| Itraconazole Sequential Therapy | Number of Participants With Comprehensive Efficacy | Improved | 16 participants |
| Itraconazole Sequential Therapy | Number of Participants With Comprehensive Efficacy | Failed | 4 participants |
Primary
Number of Participants With Mycological Efficacy
Mycological efficacy was assessed as fungi cleared: negative for fungal microscopic examination and culture (test for infection or organisms that could cause infection); fungi not cleared: positive for fungal microscopic examinations and/or culture.
Time frame: Week 6
Population: The Full analysis set (FAS) population included all participants who received at least 1 intravenous infusion or oral solution of the study drug and completed at least 1 post-baseline visit. Here 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Itraconazole Sequential Therapy | Number of Participants With Mycological Efficacy | Fungi cleared | 20 participants |
| Itraconazole Sequential Therapy | Number of Participants With Mycological Efficacy | Fungi not cleared | 10 participants |