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

Visceral Leishmaniasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03636659
• Other study ID #: CR179-17
• Secondary ID: CTRI/2018/04/013
• Status: Completed
• Phase: Phase 1
• Start date: May 2, 2018
• Est. completion date: April 5, 2019

Study information

• Verified date: August 2018
• Source: Aurobindo Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: April 5, 2019
• Est. primary completion date: April 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Visceral Leishmaniasis

Intervention

Drug:
• Amphotericin B Liposome
Manufactured for: Auromedics Pharma LLC, USA
• AmBisome (Amphotericin B) Liposome
Marketed by: Astellas Pharma US, Inc. USA

Locations

Country	Name	City	State
Bangladesh	International Centre for Diarrhoeal Disease Research b	Dhaka
India	Kala-Azar medical Research Centre	Muzaffarpur	Bihar
India	Rajendra Memorial Research Institute of Medical Sciences	Patna	Bihar

Sponsors (2)

Lead Sponsor	Collaborator
Aurobindo Pharma Ltd	Axis Clinicals Limited

Countries where clinical trial is conducted

Bangladesh,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimation of Cmax-ss, Maximum concentration over the steady state dosing interval	To establish bioequivalence limits within 80-125 %	05 days
Primary	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	Evaluation of Cmin-ss	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days
Secondary	Evaluation of Cavg-ss	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days
Secondary	Evaluation of tmax-ss	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days
Secondary	Evaluation of Cpd	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days
Secondary	Evaluation of Percentage Fluctuation	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days
Secondary	Evaluation of Swing	Summary statistics, ANOVA, Ratio Analysis, 90% Confidence Interval, Inter subject variability and Power will be calculated	05 days