Pharmacokinetics and Safety of AmBisome and DKF-5122

Phase 1

Completed

• Conditions: Invasive Fungal Infections; Neutropenic Fever
• Interventions: Drug: AmBisome; Drug: DKF-5122

• Registration Number: NCT05749380
• Lead Sponsor: Dongkook Pharmaceutical Co., Ltd.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-07
• Primary Completion: 2022-01-28
• Study Completion: 2022-01-28
• Status Verified: 2023-02
• Study First Submitted: 2023-02-16
• Study First Submitted QC: 2023-02-26
• Last Update Submitted: 2023-02-26
• Study First Posted: 2023-03-01
• Last Update Posted: 2023-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1A(RT)	DKF-5122	Patients (AmBisome, DKF-5122)
2A(RT)	DKF-5122	Healthy subjects (AmBisome, DKF-5122)
1B(TR)	DKF-5122	Patients (DKF-5122, AmBisome)
2B(TR)	DKF-5122	Healthy subjects (DKF-5122, AmBisome)
1B(TR)	AmBisome	Patients (DKF-5122, AmBisome)
1A(RT)	AmBisome	Patients (AmBisome, DKF-5122)
2A(RT)	AmBisome	Healthy subjects (AmBisome, DKF-5122)
2B(TR)	AmBisome	Healthy subjects (DKF-5122, AmBisome)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
tmax	0 to 93 hr	Liposome encapsulated amphotericin B and Unbound Amphotericin B of healthy adult
tmax,ss	0 to 93 hr	Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient
Cmax	0 to 93 hr	Unbound Amphotericin B of healthy adult
AUCinf	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
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
AUClast	0 to 93 hr	Unbound Amphotericin B of healthy adult
V/F	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 indication patient
Cmin,ss	0 to 93 hr	Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient
Cav,ss	0 to 93 hr	Liposome encapsulated amphotericin B and Unbound Amphotericin B of indication patient

Trial Locations

Locations (1)

The Catholic University of Korea Seoul St. Mary's Hospital; 🇰🇷 Seoul, Seocho-gu, Korea, Republic of