Invasive Fungal Infections, Neutropenic Fever
Conditions
Brief summary
The purpose of the study is to assess the Safety and Pharmacokinetic Characteristics of AmBisome and DKF-5122
Interventions
DRUGAmBisome
Reference, dose of 3 mg/kg.
DRUGDKF-5122
Test, dose of 3 mg/kg
Sponsors
Dongkook Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Part 1. Patients 1. Age 19 years and older 2. Empirical therapy for presumed fungal infection in febrile, neutropenic patients 3. Voluntarily decided to participate in the study and signed the informed consent form 4. Having contraception during the study * Part 2. Healthy subjects 1. Age 19 to 45 years 2. Body weight 55 kg or more, within ±20% of the ideal body weight 3. Having no congenital or chronic disease within the last 5 years. 4. Voluntarily decided to participate in the study and signed the informed consent form 5. Having contraception during the study
Exclusion criteria
* Part 1. Patients 1. Clinically significant conditions that may affect the pharmacokinetics of amphotericin 2. History of diseases that may affect the pharmacokinetics of amphotericin 3. History of drug abuse 4. History of hypersensitivity to ingredients of investigational products 5. Unable to maintain proper contraception 6. Pregnant or breast-feeding 7. The following laboratory test results at screening * Hemoglobin \< 8.0 g/dL * Serum Creatinine \> 2x the UNL * AST or ALT \> 10x UNL * Systolic blood pressure ≥ 140 mmHg or ≤ 90 mmHg * Diastolic blood pressure ≥ 90 mmHg or ≤ 60 mmHg 8. Before the first administration of investigational products * Participation to other clinical trials within 6 months * Whole blood donation within 60 days or component within 30 days * (Herbal) medicines that may affect the pharmacokinetics of amphotericin within 14 days * Grapefruit-containing foods within 7 days * Excessive exercise within 7 days 9. Excessive caffeine and alcohol consumption, or a smoker 10. Not eligible due to other reasons at the investigator's discretion * Part 2. Healthy subjects 1. Clinically significant disorders or a medical history of active cardiovascular, respiratory , kidney, endocrine, hematological, digestive, central nervous system, psychiatric disease, or malignant tumor 2. Clinically significant conditions that may affect the pharmacokinetics of amphotericin 3. History of diseases that may affect the pharmacokinetics of amphotericin 4. History of drug abuse 5. History of hypersensitivity to ingredients of investigational products 6. Unable to maintain proper contraception 7. Pregnant or breast-feeding 8. The following laboratory test results at screening * Hemoglobin \< 13.0 g/dL * Serum Creatinine \> 1.25 x UNL * eGFR \< 90 mL/min/1.73 m2 * AST or ALT \> 1.25 x UNL * Total bilirubin \> 1.25 x UNL * CPK \> 1.5 x UNL * Systolic blood pressure ≥140 mmHg or ≤90 mmHg * Diastolic blood pressure ≥ 90 mmHg or ≤60 mmHg * Arrhythmia 9. Before the first administration of investigational products * Participation to other clinical trials within 6 months * Whole blood donation within 60 days or component within 30 days * Drugs that induce or inhibit drug metabolism enzymes within 30 days * Vaccination within 7 days * Prescription drugs, herbal medicines, over-the-counters, or vitamins within 14 days * Grapefruit-containing foods within 7 days * Excessive exercise within 7 days 10. Excessive caffeine and alcohol consumption, or a smoker 11. Not eligible due to other reasons at the investigator's discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0 to 93 hr | Liposome encapsulated amphotericin B of healthy adult |
| AUClast | 0 to 93 hr | Liposome encapsulated amphotericin B of healthy adult |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult |
| tmax | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult |
| t1/2 | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult |
| CL/F | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult |
| V/F | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult |
| Cmax | 0 to 93 hr | Unbound Amphotericin B of healthy adult |
| Cav,ss | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| tmax,ss | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| PTF (peak to trough fluctuation ratio) | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| CLss/F | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| Vd,ss/F | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| Cmin,ss | 0 to 93 hr | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient |
| AUClast | 0 to 93 hr | Unbound Amphotericin B of healthy adult |
Countries
South Korea
Outcome results
None listed