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

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

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

Study Overview

• Status: Completed
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Drug: Amphotericin B Liposome; Drug: AmBisome (Amphotericin B) Liposome

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1212
    • International Centre for Diarrhoeal Disease Research b
• India
  • Bihar
    • Muzaffarpur, Bihar, India, 842001
      • Kala-azar Medical Research Centre
    • Patna, Bihar, India, 800007
      • Rajendra Memorial Research Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amphotericin B Liposome; 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; Manufactured for: Auromedics Pharma LLC, USA
Active Comparator: AmBisome Liposome; 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; Marketed by: Astellas Pharma US, Inc. USA; Other Names: AmBisome

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aurobindo Pharma Ltd
• Collaborators: Axis Clinicals Limited
• Investigators: Study Chair: Nagesh Meda, M.Pharm, Aurobindo Pharma Ltd; Study Director: Dr. Subhra Lahiri, Ph.D, Axis Clinicals Limited; Study Director: Dr. Sajid Mohd, MD, Axis Clinicals Limited; Principal Investigator: Dr. Krishna Pandey, MD, Rajendra Memorial Research Institute of Medical Sciences; Principal Investigator: Dr. Shyam Sundar, MD, Kala-azar Medical Research Centre; Principal Investigator: Dr. Dinesh Mondal, MD, International Centre for Diarrhoeal Disease Research b

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2018
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): April 5, 2019

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 26, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: CR179-17; CTRI/2018/04/013350 (Other Identifier: India Council of Medical Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes