A Pilot Bioequivalence Study Between Amphotericin B Liposome for Injection and AmBisome® in Healthy Subjects

Study Overview
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Brief Summary
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The 2 × 2 crossover designed study is to evaluate the bioequivalence of two different amphotericin B liposome for injection after single IV infusion at the same dose in normal healthy subjects.

Official Title
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A Randomized, Open-label, Two-preparation, Single-dose, Two-sequence Pilot Bioequivalence Study Between Amphotericin B Liposome for Injection and AmBisome® in Healthy Subjects

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: Amphotericin B liposome for injection
* Drug: AmBisome®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects fully understand and voluntarily participate in this study and sign informed consent. Healthy female and male volunteers aged 18-55 years. Body weight ≥ 50 kg for male and ≥ 45 kg for female with a body mass index (BMI) in the range of 19.0 to 26.0 kg/m2 (inclusive). Subjects must be in good health on the basis of medical history, physical examination, electrocardiogram, chest X-ray, and routine laboratory evaluations. Able to communicate well with the investigator and comply with the requirements of the study. Exclusion Criteria: History of allergic reactions to amphotericin B or its analogs. History of allergy to two or more kinds of drugs or food. Subjects have any history of surgery, trauma that may affect the safety of the study or the intracorporal process of the drug, or have a surgical schedule during the study period. Use of any prescription or over the counter medication within 14 days prior to screening. History of drug abuse within 6 months prior to screening. Smoking more than 5 cigarettes per day within 3 months prior to screening, or unable to stop using any tobacco products during the trial period. Consumption of alcohol in excess of 14 units/week within 3 months prior to screening. Consumption excessive amounts of tea, coffee and/or caffeine-rich beverages daily within 3 months prior to screening. Participation in other trial within 3 months prior to screening. Donation or loss of more than 400 mL blood within 3 months prior to screening. Subject (female) is lactating or pregnant. Subject who cannot tolerate venipuncture or have a history of needle and blood sickness. Subject who has special requirements on diet and cannot accept the uniform diet. Subject who has childbearing plan, unwillingness or inability to use effective contraceptives from 2 weeks before the screening to 6 months after the last dosing of the study drug. Any positive test result for Hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti-syphilis spirochete. Female subjects with positive pregnancy test results during the screening period or during the study. Positive test result for alcohol screening or drug abuse. AST or ALT, total or direct bilirubin, alkaline phosphatase and creatinine are above the upper limit of normal and potassium is below the lower limit of normal; any other abnormalities in laboratory tests and ancillary tests that are judged by the investigator to be clinically significant. Not suitable for this study as determined by the investigator due to other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence TR<br>6 healthy subjects assigned to the sequence TR were administrated intravenously for 120 mins with the test product of amphotericin B liposome for injection in period 1 and the reference product of AmBisome® in period 2. | Drug: Amphotericin B liposome for injection<br>* IV infusion<br>* Other names: the test product;Drug: AmBisome®<br>* IV infusion<br>* Other names: the reference product;|
| Experimental: Sequence RT<br>6 healthy subjects assigned to the sequence RT were administrated intravenously for 120 mins with the reference product of AmBisome® in period 1 and the test product of amphotericin B liposome for injection in period 2. | Drug: Amphotericin B liposome for injection<br>* IV infusion<br>* Other names: the test product;Drug: AmBisome®<br>* IV infusion<br>* Other names: the reference product;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence based on Cmax | 90% CI of Cmax of liposome-encapsulated and non-liposome-encapsulated Amphotericin B between Amphotericin B liposome for injection and AmBisome® within 80.00% 125.00%. | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| Bioequivalence based on AUC0-t | 90% CI of AUC0-t of liposome-encapsulated andnon-liposome-encapsulated Amphotericin B between Amphotericin B liposome for injection and AmBisome® within 80.00% 125.00%. | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| Bioequivalence based on AUCinf | 90% CI of AUC0-∞ of liposome-encapsulated and non-liposome-encapsulated Amphotericin B between Amphotericin B liposome for injection and AmBisome® within 80.00% 125.00%. | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of liposome-encapsulated and non-liposome-encapsulated Amphotericin B | Time of maximum observed concentration | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| t1/2 of liposome-encapsulated and non-liposome-encapsulated Amphotericin B | Terminal elimination half-life | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| λz of liposome-encapsulated and non-liposome-encapsulated Amphotericin B | Apparent elimination rate constant | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| Residual area of liposome-encapsulated and non-liposome-encapsulated Amphotericin B | Extrapolated area | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion | 
| Number of treatment-emergent adverse events for the test and the reference products |  | predose, 0.5, 1.0, 1.5, 2.0,2.25,2.5,3.0,4.0,6.0,8.0,10.0,14.0,26.0,50.0,74.0,146,218,290,362,434,506,578,674 hours after intravenous infusion |