Pharmacokinetics and Safety of AmBisome and DKF-5122

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the Safety and Pharmacokinetic Characteristics of AmBisome and DKF-5122

Official Title
-----------------
Bioequivalence Study to Evaluate Pharmacokinetics and Safety of AmBisome and DKF-5122 in Indicated Patients and Healthy Adults

Conditions
-----------------
Invasive Fungal Infections, Neutropenic Fever

Intervention / Treatment
-----------------
* Drug: AmBisome
* Drug: DKF-5122


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part 1. Patients Age 19 years and older Empirical therapy for presumed fungal infection in febrile, neutropenic patients Voluntarily decided to participate in the study and signed the informed consent form Having contraception during the study Part 2. Healthy subjects Age 19 to 45 years Body weight 55 kg or more, within ±20% of the ideal body weight Having no congenital or chronic disease within the last 5 years. Voluntarily decided to participate in the study and signed the informed consent form Having contraception during the study Exclusion Criteria: Part 1. Patients Clinically significant conditions that may affect the pharmacokinetics of amphotericin History of diseases that may affect the pharmacokinetics of amphotericin History of drug abuse History of hypersensitivity to ingredients of investigational products Unable to maintain proper contraception Pregnant or breast-feeding 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 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 Excessive caffeine and alcohol consumption, or a smoker Not eligible due to other reasons at the investigator's discretion Part 2. Healthy subjects Clinically significant disorders or a medical history of active cardiovascular, respiratory , kidney, endocrine, hematological, digestive, central nervous system, psychiatric disease, or malignant tumor Clinically significant conditions that may affect the pharmacokinetics of amphotericin History of diseases that may affect the pharmacokinetics of amphotericin History of drug abuse History of hypersensitivity to ingredients of investigational products Unable to maintain proper contraception Pregnant or breast-feeding 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 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 Excessive caffeine and alcohol consumption, or a smoker Not eligible due to other reasons at the investigator's discretion

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1A(RT)<br>Patients (AmBisome, DKF-5122) | Drug: AmBisome<br>* Reference, dose of 3 mg/kg.<br>Drug: DKF-5122<br>* Test, dose of 3 mg/kg<br>|
| Other: 1B(TR)<br>Patients (DKF-5122, AmBisome) | Drug: AmBisome<br>* Reference, dose of 3 mg/kg.<br>Drug: DKF-5122<br>* Test, dose of 3 mg/kg<br>|
| Other: 2A(RT)<br>Healthy subjects (AmBisome, DKF-5122) | Drug: AmBisome<br>* Reference, dose of 3 mg/kg.<br>Drug: DKF-5122<br>* Test, dose of 3 mg/kg<br>|
| Other: 2B(TR)<br>Healthy subjects (DKF-5122, AmBisome) | Drug: AmBisome<br>* Reference, dose of 3 mg/kg.<br>Drug: DKF-5122<br>* Test, dose of 3 mg/kg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Liposome encapsulated amphotericin B of healthy adult | 0 to 93 hr | 
| AUClast | Liposome encapsulated amphotericin B of healthy adult | 0 to 93 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| AUClast | Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| AUCinf | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| tmax | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| t1/2 | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| CL/F | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| V/F | Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult | 0 to 93 hr | 
| Cmin,ss | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| Cav,ss | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| tmax,ss | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| t1/2 | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| PTF (peak to trough fluctuation ratio) | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| CLss/F | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr | 
| Vd,ss/F | Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient | 0 to 93 hr |