A Pilot Bioequivalence Study Between Amphotericin B Liposome for Injection and AmBisome® in Healthy Subjects
Phase 1
Completed
- Conditions
- Bioequivalence
- Interventions
- Registration Number
- NCT04993222
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence TR Amphotericin B liposome for injection 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. Sequence TR AmBisome® 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. Sequence RT AmBisome® 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. Sequence RT Amphotericin B liposome for injection 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.
- Primary Outcome Measures
Name Time Method Bioequivalence based on Cmax 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 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%.
Bioequivalence based on AUC0-t 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 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%.
Bioequivalence based on AUCinf 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 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%.
- Secondary Outcome Measures
Name Time Method Tmax of liposome-encapsulated and non-liposome-encapsulated Amphotericin B 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 Time of maximum observed concentration
t1/2 of liposome-encapsulated and non-liposome-encapsulated Amphotericin B 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 Terminal elimination half-life
λz of liposome-encapsulated and non-liposome-encapsulated Amphotericin B 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 Apparent elimination rate constant
Residual area of liposome-encapsulated and non-liposome-encapsulated Amphotericin B 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 Extrapolated area
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
Trial Locations
- Locations (1)
Wuhan Medical Treatment Center
🇨🇳Wuhan, Hubei, China