An Bioequivalence Study to Compare Two 2 mg/ml Liposomal Amphotericin B Injections in Healthy Subjects

An Open-label, Randomized, Balanced, Crossover Bioequivalence Study to Compare Two 2 mg/ml Liposomal Amphotericin B Injections in Healthy Subjects

The 2 × 2 crossover designed study is to evaluate the bioequivalence of two different liposomal amphotericin B injections after single IV infusion at the same dose in normal healthy subjects.

Study Overview

• Status: Completed
• Conditions: Normal Healthy Subjects
• Intervention / Treatment: Drug: AmBisome; Drug: Liposomal Amphotericin B

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be adults (> 20 years old) in good health on the basis of medical history, physical examination, electrocardiogram, chest X-ray, and routine laboratory evaluations.
2. Vital signs (after 3 minutes resting in a upright position) which are within the following ranges: Ear body temperature between 35.0-37.5 °C. Systolic blood pressure, 90-140 mm Hg. Diastolic blood pressure, 50-90 mm Hg. Pulse rate, 50-90 bpm
3. Fasting blood glucose < 100 mg/dL.
4. Body weight must be above 50 kg for men and 45 kg for women and within 20% of ideal body weight.
5. Negative urine drug screen at clinic check-in before each dosing
6. Able to sign informed consent prior to study.
7. Able to communicate well with the investigator and comply with the requirements of the study.
8. Pregnancy tests (female only): negative reaction

Exclusion Criteria:

1. Use of any prescription or over the counter medication within 14 days prior to investigational products administration; with the exception of acetaminophen (not more than 2 g/day) or vitamins.
2. A plan to take concomitant medications while enrolled in the study, with the exception of acetaminophen (not more than 2 g/day) or vitamins.
3. Presence of any acute or chronic medical condition within 2 weeks prior to investigational products administration, including but not limited to: hepatic, gastrointestinal, renal, hematologic (including coagulation), pulmonary, neurologic, respiratory, endocrine, or cardiovascular system abnormalities; psychiatrical disease including major psychiatric disorders (e.g., schizophrenia, bipolar disorder); acute infection; or other conditions that would interfere with the absorption, distribution, metabolism, or excretion of drugs. Evidence of impaired renal function as indicated by clinically significant abnormal creatinine or BUN values or abnormal urinary constituents (e.g., albuminuria) as judged by the investigator. Evidence of liver disease, hepatitis B, hepatitis C or liver injury as indicated by an clinically significant abnormal liver function profile such as GOT, GPT, g-GT, alkaline phosphatase, serum bilirubin, HBs Ag, or HCV Ab as judged by the investigator.
4. Hemoglobin less than 12 g/dL
5. Participation in any clinical investigation within 2 months or 5 half-lives, whichever is longer, prior to investigational products administration.
6. Donation or loss of more than 500 mL blood within 3 months prior to investigational products administration.
7. Subject is known for HIV infected.
8. Known allergy or hypersensitivity to amphotericin B or its analogs.
9. History of drug or alcohol abuse within 12 months prior to investigational products administration ; current consumption of alcohol in excess of 28 units/week (one unit is 6 oz of beer, ½ oz of hard liquor, or 2 oz of wine)
10. Subjects who, in the opinion of the investigator, should not participate in the study or may not be capable of following the study schedule for any reason.
11. Consumption of more than 36 to 40 oz (1.1-1.2 L) of caffeine-containing beverages per day
12. Consumption of any products containing grapefruit in the 3 days before clinic check-in.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liposomal Amphotericin B; Generic drug	Drug: Liposomal Amphotericin B
Active Comparator: AmBisome; RLD	Drug: AmBisome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The bioequivalence of two different liposomal amphotericin B injections	90% CI of Cmax and AUCinf of Liposomal and non-liposomal Amphotericin B between Ambil and AmBisome within 80.00%~125.00%.	14 days

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company

Publications and helpful links

General Publications

• Adler-Moore JP, Gangneux JP, Pappas PG. Comparison between liposomal formulations of amphotericin B. Med Mycol. 2016 Mar;54(3):223-31. doi: 10.1093/mmy/myv111. Epub 2016 Jan 14.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 20, 2012
• First Submitted That Met QC Criteria: July 27, 2012
• First Posted (Estimate): July 30, 2012

Study Record Updates

• Last Update Posted (Estimate): November 27, 2013
• Last Update Submitted That Met QC Criteria: November 25, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: TLC166.2