Invasive Fungal Infections, Neutropenic Fever, Visceral Leishmaniasis
Conditions
Brief summary
Single-center, randomized, open-label, single-dose, two-treatment, two-period, two-sequence crossover design to evaluate the human bioequivalence of two Amphotericin B Liposome for Injection formulations
Detailed description
To evaluate the human bioequivalence of Amphotericin B Liposome for Injection (strength: 50 mg) provided by Sichuan Huiyu Pharmaceutical Co., Ltd. and Amphotericin B Liposome for Injection (trade name: Ambisome®, strength: 50 mg, MAH: Gilead Sciences) by comparing the differences in the extent and rate of absorption between the two formulations in a healthy Chinese population under a single-center, randomized, open-label, single-dose, two-treatment, two-period, two-sequence crossover design.
Interventions
DRUGAmphotericin B Liposome for Injection (strength: 50 mg, Sichuan Huiyu Pharmaceutical Co., Ltd.)
Single intravenous administration of 3.0 mg/kg in each period.
DRUGAmphotericin B Liposome for Injection (trade name: Ambisome®, strength: 50 mg, MAH: Gilead Sciences)
Single intravenous administration of 3.0 mg/kg in each period.
Sponsors
Sichuan Huiyu Pharmaceutical Co., Ltd
Changsha King-eagle Med Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
The enrolled participants shall meet all of the following criteria: 1. The study participants must give informed consent before the trial, fully understand the content, process and possible adverse reactions, and voluntarily sign a written informed consent; 2. The study participants can communicate well with the investigators and complete the trial according to protocol; 3. Sex: female or male; age: 18-50 years (inclusive); 4. Body Mass Index (BMI): 19-28 kg/m2 (inclusive), with a minimum weight of 50.0 kg for males and 45.0 kg for females (BMI = Body weight / Height2 \[kg/m2\]).
Exclusion criteria
Study participants meeting one or more of the following criteria will be excluded: 1. Allergic constitution (such as those allergic to two or more drugs or foods \[e.g., milk\], or pollen), or known history of allergy to the components of the study drug or similar drugs (API: amphotericin B; excipients: hydrogenated soy phosphatidylcholine, cholesterol, distearoylphosphatidylglycerol \[sodium salt\], alpha tocopherol, sucrose, disodium succinate hexahydrate, hydrochloric acid, and sodium hydroxide); (inquiry) 2. Subjects with the following diseases of clinical significance (including but not limited to diseases related to respiratory system, circulatory system, digestive system, blood system, endocrine system, immune system, skin system, psycho-neurological system, ophthalmology and otorhinolaryngology); (inquiry) 3. Subjects with gastrointestinal, liver and kidney diseases that affect the pharmacokinetics of drugs; (inquiry) 4. Subjects who underwent major surgery within 6 months prior to initial administration, or who planned to undergo surgery during the study; (inquiry) 5. Clinically significant abnormalities in vital signs, physical examination, electrocardiogram and laboratory tests (blood biochemistry, hematology, urinalysis, coagulation); (as determined by the clinical investigator) 6. Subjects with a history of hepatitis B, hepatitis C, AIDS (Acquired Immune Deficiency Syndrome), syphilis and/or abnormalities in one or more of the four tests for infectious diseases with clinical significance; (as determined by the clinical investigator) 7. Blood loss or blood donation of greater than or equal to 400 mL within 3 months prior to initial administration (except for female menstrual period), and/or platelet donation within 2 weeks prior to initial administration; (inquiry) 8. Use of any prescription medicine within 14 days prior to initial administration or use of any over-the-counter medicine, Chinese herbal medicine or health product within 7 days prior to initial administration (except for topical drugs with local effects); (inquiry) 9. Use of azoles (e.g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.), skeletal muscle relaxants, corticosteroids and adrenal cortical hormones, antineoplastic agents, digitonin, flucytosine or other nephrotoxic medications within 28 days prior to initial administration; (inquiry) 10. Subjects who received vaccines or live attenuated vaccines within 4 weeks prior to the administration of the study drug, or who planned to be vaccinated during the trial; (inquiry) 11. Subjects who received medication in any clinical trial or participated in any medical device clinical trial within 3 months prior to initial administration; (inquiry + online screening) 12. A history of drug abuse within 5 years, and/or drug use within 3 months prior to screening, and/or habitual use of any drug (including Chinese herbs) or positive urine drug screening; (inquiry + as determined by the clinical investigator) 13. Subjects who smoked more than 5 cigarettes per day within 3 months prior to screening and/or did not agree to refrain from using any tobacco products during the trial; (inquiry) 14. Regular drinkers within 6 months prior to screening, i.e., subjects who drank more than 14 units of alcohol per week (1 unit = 360 mL of beer with 5% alcohol or 45 mL of spirits with 40% alcohol or 150 mL of wine with 12% alcohol), or subjects who did not agree to stop drinking alcohol 48 h prior to initial administration and during the trial, or test positive for breath alcohol; 15. Subjects who consume excessive amounts of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup = 250 mL) per day within 6 months prior to screening, and/or do not agree that tea, coffee and/or caffeinated foods, grapefruit and/or grapefruit juice, and/or products containing opium poppy are prohibited 48 h prior to initial administration and during the trial; (inquiry) 16. Subjects who have a birth plan (including sperm or egg donation) and/or do not agree to take effective contraceptive methods (non-drug during the trial period) from signing informed consent form to 6 months after the final administration; (inquiry) 17. Pregnant or lactating women or subjects with positive pregnancy results; (inquiry, for females only) 18. Subjects who have used oral contraceptives within 30 days prior to initial administration; (inquiry) 19. Use of long-acting estrogen and/or progesterone injections and/or implants within 6 months prior to initial administration; (inquiry, females only) 20. Women of childbearing age who have unprotected sex with their partner within 14 days prior to initial administration; (inquiry, females only) 21. Subjects who cannot tolerate venipuncture or have a history of needle and blood sickness; (inquiry) 22. Subjects who may not be able to complete the study for other reasons or who the investigator considers should not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0 hour before safe dose and 0 hour before formal dose to 1320 hours post formal dose | 90% confidence interval is within the 80.00%-125.00% equivalence margin. |
| AUC0-t | 0 hour before safe dose and 0 hour before formal dose to 1320 hours post formal dose | 90% confidence interval is within the 80.00%-125.00% equivalence margin. |
| AUC0-∞ | 0 hour before safe dose and 0 hour before formal dose to 1320 hours post formal dose | 90% confidence interval is within the 80.00%-125.00% equivalence margin. |
| AUC0-10h | 0 hour before safe dose and 0 hour before formal dose to 1320 hours post formal dose | 90% confidence interval is within the 80.00%-125.00% equivalence margin. |
| AUC10-last | 0 hour before safe dose and 0 hour before formal dose to 1320 hours post formal dose | 90% confidence interval is within the 80.00%-125.00% equivalence margin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 0 h before safe dose and 0 h before formal dose to 1320 hours post formal dose | 90% confidence intervals will also be investigated as supportive data. |
| λz | 0 h before safe dose and 0 h before formal dose to 1320 hours post formal dose | 90% confidence intervals will also be investigated as supportive data. |
| t1/2 | 0 h before safe dose and 0 h before formal dose to 1320 hours post formal dose | 90% confidence intervals will also be investigated as supportive data. |
| AUC_%Extrap | 0 h before safe dose and 0 h before formal dose to 1320 hours post formal dose | 90% confidence intervals will also be investigated as supportive data. |
Countries
China
Contacts
STUDY_DIRECTORQing Wen
Jinan Central Hospital
Outcome results
None listed