Clinical trial NCT03636659: Steady State Global Bioequivalence Study of Amphotericin B Liposome for Injection 50 mg/ Vial in Fed Condition
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Visceral Leishmaniasis
Lead sponsor: Aurobindo Pharma Ltd
Sponsor class: INDUSTRY
Collaborators: name: Axis Clinicals Limited
First posted: 2018-08-17
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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).

Eligibility criteria: 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

Primary outcomes:
measure: Estimation of Cmax-ss, Maximum concentration over the steady state dosing interval
timeFrame: 05 days
measure: Estimation of AUC0-tau, Area under the plasma concentration time curve over the steady state dosing interval
timeFrame: 05 days
Secondary outcomes:
measure: Evaluation of Cmin-ss
timeFrame: 05 days
measure: Evaluation of Cavg-ss
timeFrame: 05 days
measure: Evaluation of tmax-ss
timeFrame: 05 days
measure: Evaluation of Cpd
timeFrame: 05 days
measure: Evaluation of Percentage Fluctuation
timeFrame: 05 days
measure: Evaluation of Swing
timeFrame: 05 days
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research b
city: Muzaffarpur
country: India
facility: Kala-Azar medical Research Centre
state: Bihar
city: Patna
country: India
facility: Rajendra Memorial Research Institute of Medical Sciences
state: Bihar
Study officials:
affiliation: Aurobindo Pharma Ltd
name: Nagesh Meda, M.Pharm
role: STUDY_CHAIR
affiliation: Axis Clinicals Limited
name: Dr. Subhra Lahiri, Ph.D
role: STUDY_DIRECTOR
affiliation: Axis Clinicals Limited
name: Dr. Sajid Mohd, MD
role: STUDY_DIRECTOR
affiliation: Rajendra Memorial Research Institute of Medical Sciences
name: Dr. Krishna Pandey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kala-Azar medical Research Centre
name: Dr. Shyam Sundar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research b
name: Dr. Dinesh Mondal, MD
role: PRINCIPAL_INVESTIGATOR
References: