| CTRI Number |
CTRI/2009/091/000058 [Registered on: 13/03/2009] |
| Last Modified On: |
26/12/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
Public Title of Study
Modification(s)
|
Comparing the treatments of Two Different Lipid preparations of Amphotericin B for the treatment of Kala Azar |
Scientific Title of Study
Modification(s)
|
A Prospective, Multicentric, Randomized, Two Arm, Open Label Phase III Study To Assess Efficacy And Safety Of Infusion Of Amphomul® (Amphotericin B Emulsion) As Compared To AmBisome In Patients Of Visceral Leishmaniasis (Kala Azar) |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| BSV-AMBE-III-KA-0908 |
Protocol Number |
| NCT00876824 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Gautam Daftary |
| Designation |
Managing Director |
| Affiliation |
Bharat Serums and Vaccines Ltd. |
| Address |
Bharat Serums and Vaccines Ltd,
17th floor, Hoechst House, Nariman Point
Mumbai
MAHARASHTRA
400021
India |
| Phone |
02266560925 |
| Fax |
02266560901 |
| Email |
gautam.daftary@bharatserums.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Gautam Daftary |
| Designation |
Managing Director |
| Affiliation |
Bharat Serums and Vaccines Ltd. |
| Address |
Bharat Serums and Vaccines Ltd,
17th floor, Hoechst House, Nariman Point
Mumbai
MAHARASHTRA
400021
India |
| Phone |
02266560925 |
| Fax |
02266560901 |
| Email |
gautam.daftary@bharatserums.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Taref Kanthawala |
| Designation |
General Manager - Clinical Research |
| Affiliation |
Bharat Serums and Vaccines Ltd. |
| Address |
Bharat Serums and Vaccines Ltd,
17th floor, Hoechst House, Nariman Point
Mumbai
MAHARASHTRA
400021
India |
| Phone |
|
| Fax |
|
| Email |
taref.kanthawala@bharatserums.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Bharat Serums & Vaccines Limited |
|
Primary Sponsor
Modification(s)
|
| Name |
Bharat Serums and Vaccines Ltd |
| Address |
17th floor, Hoechst House
Nariman Point
Mumbai 400021 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
Details of Secondary Sponsor
Modification(s)
|
|
Countries of Recruitment
Modification(s)
|
India |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. C. P. Thakur |
Balaji Utthan Sansthan |
, Kala Azar Research Centre,Uma Complex, Fraser Road-800001
Patna
BIHAR |
09835239319
thakurcp@gmail.com |
| Dr. Shyam Sundar |
Kala-azar Medical Research Center |
Rambag Road,-842001
Muzaffarpur
BIHAR |
05422309493
drshyamsundar@hotmail.com |
| Dr. T. K. Jha |
Kalazar Research Center |
Brahmpura,-842003
Muzaffarpur
BIHAR |
09431238088
dr_tkjha@hotmail.com |
| Dr. Krishna Pandey |
Rajendra Memorial Research Institute |
Agamkuan,-800007
Patna
BIHAR |
06122631565
drkrishnapandey@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Ethics Committee, Patna - 800007 |
Approved |
| Ethics Committee,Muzaffarpur-842 001 |
Approved |
| Ethics Committee,Muzaffarpur-842 003 |
Approved |
| Ethics Committee,Patna-800 001 |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B550||Visceral leishmaniasis, Visceral Leishmaniasis (Kala Azar), |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Amphotericin B Emulsion (Amphomul) |
15mg/kg single bolus dose |
| Comparator Agent |
Liposomal Amphotericin B (AmBisome) |
15mg/kg single bolus dose |
|
|
Inclusion Criteria
|
| Age From |
|
| Age To |
|
| Gender |
|
| Details |
1. Male or female patients aged between 5 to 65 years (both inclusive).
2. Patient/patient's legally acceptable representative (LAR) is willing and able to give written informed consent to participate in the study.
3. Clinical signs and symptoms of Visceral Leishmaniasis (fever of over 2 weeks duration and splenomegaly)
4. Presence of amastigotes (Leishmania-Donovani bodies) at prescreening detected by recombinant K39 protein (rK39) dipstick test with confirmation of Kala-azar by splenic or bone marrow aspirate smear examination.
5. No previous treatment for Visceral Leishmaniasis within 30 days from screening.
6. Non-pregnant, non-lactating females of age equal to or greater than 5 years, and woman of childbearing potential (any woman who has reached menarche) who are willing to use acceptable methods of contraception like long term acting injections ex. Depo-Provera.
7. Negative Urine pregnancy test (UPT) in all women physiologically capable of becoming pregnant (any woman who has reached menarche)
8. Hemoglobin equal to or greater than 5 g/dL
9. White blood cells (WBC) count equal to or greater than 1000/cmm
10. Platelet count equal to or greater than 50000/cmm
11. Alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase equal to or less than 2.5 times the upper limit of normal (ULN)
12. Prothrombin time equal to or less than 4 seconds above the control.
13. Normal serum creatinine and serum potassium levels
14. Negative tests for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) and Hepatitis B surface antigen (HBsAg). |
|
| ExclusionCriteria |
| Details |
1. Patients with past history of treatment with Amphotericin B or any other drug for Visceral Leishmaniasis within 30 days prior to screening.
2. Patients positive for HIV, HCV and HBsAg infection, immunocompromised patients (through history).
3. A history or evidence of any concurrent disease that may be serious or life threatening, significant hematological, cardiac, hepatic, renal, respiratory, neurological or metabolic disease or any condition which, in the opinion of the investigator, may constitute a safety concern or interfere with the evaluation of the study objectives or may prevent the patient from the completing study therapy or subsequent follow-up
4. Concurrent diabetes, tuberculosis or bacterial pneumonia (on chest X-ray, erythrocyte sedimentation rate (ESR) at screening, past history) or any other infectious or major psychiatric disease.
5. Patients with concurrent Malaria will not be included in the trial. Parascreen antigen test for detection of malarial parasites will be performed at screening visit. Patients diagnosed with malaria could be rescreened for enrollment in the trial after adequate treatment of Malaria; and if the parascreen antigen test for detection of malarial parasites is found negative then the patient could be enrolled in the trial.
6. History of major surgery within 2 weeks prior to screening
7. Blood urea nitrogen (BUN) and serum creatinine >1.5 times ULN, and serum bilirubin >1.5 times ULN
8. Proteinurea equal to or greater than 2+
9. Pregnant or nursing women
10. History of alcoholism or illicit drug use/ abuse, or any condition associated with poor compliance
11. Known hypersensitivity to Amphotericin B, inactive ingredients of Amphomul® formulation, inactive ingredients of AmBisome formulation.
12. Patients receiving any of the medications prohibited by the study protocol.
13. Simultaneous participation in another trial or received any IP less than 30 days prior to enrolment.
14. Any condition which in the investigator's opinion may prevent the patient from completing the study therapy or follow-up |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| o Definitive cure
1. Initial cure at Day 30 or Day 45
2. No signs and symptoms of relapse of Kala-azar for 6 months after study drug administration. If signs and symptoms of relapse of the disease are suspected at any time during the 6 months follow up, splenic aspirate shall be performed at 6 months or earlier after study drug administration.
Proportion of patients achieving all three-efficacy endpoints will be compared across the two groups.
|
6 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| ? Incidence of DLTs.
? Incidence of IRTs
? Incidence of nephrotoxicity and hepatotoxicity
? Number of AEs and SAEs
? Laboratory values for different parameters
|
6 months |
| 1. Incidence of DLTs.
2. Incidence of IRTs
3. Incidence of nephrotoxicity and hepatotoxicity
4. Number of AEs and SAEs
5. Laboratory values for different parameters
|
6 months |
|
Target Sample Size
Modification(s)
|
Total Sample Size="500"
Sample Size from India="500"
Final Enrollment numbers achieved (Total)= "500"
Final Enrollment numbers achieved (India)="500" |
|
Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
03/08/2009 |
| Date of Study Completion (India) |
14/01/2011 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="1"
Months="6"
Days="6" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
The study was a prospective, randomized, open-label, multicentric Phase III clinical study of Amphotericin B lipid emulsion. The main aim of the Phase III study was to demonstrate that low cost, infusion of Amphomul® 15 mg/kg/day was safe and well tolerated in the treatment of Visceral Leishmaniasis (Kala azar) as compared to AmBisome. The primary endpoint of the study was- Initial Cure with a splenic aspirate score of 0 at day 30 or day 45, clinical improvement at day 30 and no signs or symptoms of relapse at 6 months. The secondary endpoints was Incidence of Dose limiting toxicity (DLTs), Incidence of IRTs, Incidence of nephrotoxicity and hepatotoxicity, Number of AEs and SAEs, Laboratory values for different parameters evaluable at 6 months.
The non-inferiority between Amphomul® and AmBisome® was achieved in the PP population with comparable clinical improvement in both PP and MITT populations. The MITT population analysis did not meet the non-inferiority margin, which could be due to noncompliance of patients for the study-specific visits leading to major protocol deviations. Amphomul® was found to be safe and was well tolerated by the patients of Visceral Leishmaniasis (Kala-azar) in the study. In view of efficacy and safety, the study may thus conclude that the study drug Amphomul® is as efficacious as AmBisome® for the treatment of kala-azar. |