Steady State Global Bioequivalence Study of Amphotericin B Liposome for Injection 50 mg/ Vial in Fed Condition

Study Overview
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Brief Summary
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The primary objective is to determine clinical bioequivalence of Amphotericin B liposome for injection of Auromedics Pharma LLC, USA and AmBisome (Amphotericin B) liposome for injection of Astellas Pharma US, Inc., in patients with Visceral Leishmaniasis under fed condition

Detailed Description
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Multi-Center, Open-Label, Randomized, Two treatment, Parallel, Single period, Multiple-Dose, Steady state, Global Bioequivalence study of Amphotericin B Liposome for Injection 50mg /vial of Auromedics Pharma LLC, USA and AmBisome (Amphotericin B) Liposome for Injection 50mg/vial of Astellas Pharma US, inc. in patients with Visceral Leishmaniasis under fed condition.Sufficient number of patients will be enrolled to have 140 evaluable patients. (90 to 100 patients from India and 40 to 50 patients from Bangladesh).

Official Title
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Multi-Center, Open-Label, Randomized, Two Treatment, Parallel, Single Period, Multiple-Dose, Steady State, Global Bioequivalence Study of Amphotericin B Liposome for Injection 50mg /Vial in Patients With Visceral Leishmaniasis

Conditions
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Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Amphotericin B Liposome
* Drug: AmBisome (Amphotericin B) Liposome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged between 18 to 65 years (both inclusive) Clinical signs and symptoms of Visceral Leishmaniasis (fever of over 2 weeks duration, weight loss and splenomegaly) Presence of amastigotes (Leishmania Donovani bodies) at screening detected by rK39 dipstick test. Female subjects of childbearing potential must have a negative serum pregnancy test at enrolment and be willing to use a reliable method of birth control, i.e. barrier method, intrauterine device, or tubal ligation. Ability to comply with all study requirements. Patients with Hb ≥ 6.0 g/dl Patients with platelets count ≥ 60,000/mm3 Patients should be immunocompetent (e.g., white blood cell count ≥ 2500/ mm3) Patients and/ or LAR must be give written informed consent Patients with clinically acceptable results from all the screening laboratory parameters and investigations. Exclusion Criteria: Known allergy or hypersensitivity reactions to any components of conventional or liposomal Amphotericin B formulations. Any condition which the investigator thinks may prevent the patient from completing the study therapy and subsequent follow-up. Pregnant or lactating women Patients requiring dose adjustment during the study. Serum creatinine concentration greater than twice the upper limit of normal (ULN), AST or ALT value greater than 10 times the ULN Patients who are required to be on concomitant therapy with IV fat emulsions, such as total parental nutrition (TPN). Patients with total bilirubin levels > 3 times the upper normal limits (i.e. > 3.0 mg/dl). Patient with clinically significant Hematopoietic, renal, hepatic and electrolyte disorders (Low level of Magnesium and potassium) will be excluded as per the discretion of Investigator Patients with Clinically significant screening laboratory parameters in the opinion of the investigator. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent. History of uncontrolled diseases, such as thyroidal dysfunction, angina pectoralis, serious cardiac arrhythmias, serious heart failure, neuropsychiatric infection or disease. Patients with controlled and uncontrolled diabetes mellitus Patients with Uncontrolled hypertension will be excluded. Immunocompromised patients will be excluded from participating the study Patients with known positivity for human immunodeficiency virus (HIV), HBsAg and HCV. Positive results for drugs of abuse (benzodiazepines, opioids, amphetamines, cannabinoids, cocaine and barbiturates) in urine. Positive results for alcohol as detected by alcohol breath analyzer. History of difficulty with donating blood or difficulty in accessibility of veins. An unusual or abnormal diet, for whatever reason e.g. religious fasting. History of donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amphotericin B Liposome<br>Amphotericin B Liposome for Injection 50 mg/vial, intravenous infusion at a dose of 3 mg/kg/day, OD for 5 days | Drug: Amphotericin B Liposome<br>* Manufactured for: Auromedics Pharma LLC, USA<br>|
| Active Comparator: AmBisome Liposome<br>AmBisome Liposome for Injection 50 mg/ vial, intravenous infusion at a dose of 3 mg/kg/day, OD for 5 days | Drug: AmBisome (Amphotericin B) Liposome<br>* Marketed by: Astellas Pharma US, Inc. USA<br>* Other names: AmBisome;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimation of Cmax-ss, Maximum concentration over the steady state dosing interval | To establish bioequivalence limits within 80-125 % | 05 days | 
| Estimation of AUC0-tau, Area under the plasma concentration time curve over the steady state dosing interval | To establish bioequivalence limits within 80-125 % | 05 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Cmin-ss | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days | 
| Evaluation of Cavg-ss | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days | 
| Evaluation of tmax-ss | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days | 
| Evaluation of Cpd | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days | 
| Evaluation of Percentage Fluctuation | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days | 
| Evaluation of Swing | Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated | 05 days |