Pharmacokinetics and Safety of AmBisome and DKF-5122

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

The purpose of the study is to assess the Safety and Pharmacokinetic Characteristics of AmBisome and DKF-5122

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections; Neutropenic Fever
• Intervention / Treatment: Drug: AmBisome; Drug: DKF-5122

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seocho-gu
    • Seoul, Seocho-gu, Korea, Republic of, 06591
      • The Catholic University of Korea Seoul St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Dongkook Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): January 28, 2022
• Study Completion (Actual): January 28, 2022

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 26, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 26, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Hematologic Diseases; Bacterial Infections and Mycoses; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia; Mycoses; Invasive Fungal Infections; Febrile Neutropenia; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Liposomal amphotericin B
• Other Study ID Numbers: DKF-5122-BE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No