| CTRI Number |
CTRI/2009/091/000101 [Registered on: 16/12/2009] |
| Last Modified On: |
05/12/2012 |
| 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)
|
A Phase III, double-blind, randomised, multicenter trial comparing the safety and efficacy of fixed dose combination tablets of arterolane maleate and piperaquine phosphate (PQP) with Coartem® (artemether-lumefantrine tablets) in patients with acute uncomplicated Plasmodium falciparum malaria |
Scientific Title of Study
Modification(s)
|
A Phase III, double-blind, randomised, multicenter trial comparing the safety and efficacy of fixed dose combination tablets of arterolane maleate and piperaquine phosphate (PQP) with Coartem® (artemether-lumefantrine tablets) in patients with acute uncomplicated Plasmodium falciparum malaria |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| R11160083002 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Nilanjan Saha |
| Designation |
Sponsors Representative |
| Affiliation |
|
| Address |
Department of Medical Affairs and Clinical Research Ranbaxy Laboratories Ltd R&D IV 77B Sector 18
Gurgaon
HARYANA
122015
India |
| Phone |
911244194340 |
| Fax |
911244016855 |
| Email |
nilanjan.saha@ranbaxy.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Nilanjan Saha |
| Designation |
|
| Affiliation |
Ranbaxy Laboratories Limited |
| Address |
Department of Medical Affairs and Clinical Research, Ranbaxy Laboratories Ltd., R&D IV, 77-B, Sector 18
Gurgaon
HARYANA
Haryana
India |
| Phone |
91-124-4194340 |
| Fax |
91-124-2342018 |
| Email |
nilanjan.saha@ranbaxy.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Nilanjan Saha |
| Designation |
Sponsor Representative |
| Affiliation |
|
| Address |
Department of Medical Affairs and Clinical Research, Ranbaxy Laboratories Ltd R&D IV 77B Sector 18
Gurgaon
HARYANA
122015
India |
| Phone |
911244194340 |
| Fax |
911242342018 |
| Email |
nilanjan.saha@ranbaxy.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Ranbaxy Laboratories Ltd. INDIA |
|
Primary Sponsor
Modification(s)
|
| Name |
Ranbaxy Laboratories Ltd |
| Address |
Plot No. 20, Sector 18 Udyog Vihar Industrial Area Gurgaon 122015 Haryana INDIA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
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| Name |
Address |
| Department of Science and Tecnology Govt Of India |
|
|
Countries of Recruitment
Modification(s)
|
India
Thailand
Cote d'Ivoire
Democratic Republic of the Congo
Mali
Mozambique
Senegal |
Sites of Study
Modification(s)
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| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. TK Bose |
Community Welfare Society Hospital, Rourkela, Orissa |
Jagda, Rourkela,-769042
|
91 661 2473803
cwshnimr@gmail.com |
| Dr. BHK Rao |
Government Wenlock District Hospital, Mangalore, Karnataka |
,-575 001
Bangalore
KARNATAKA |
91 9845159036
raobhk@yahoo.co.in |
| Dr Sanjib Mohanty |
Ispat General Hospital, |
Rourkela 769 002 (Orissa), India
Sundargarh
ORISSA |
916612648252
916612648252
sanjibmalaria@rediffmail.com |
| Dr. B Shahi |
Mahadevi Birla Hospital & Research Center, Mahilong, Nankum, Ranchi, Jharkhand |
,-
Ranchi
JHARKHAND |
9868802083
shahibh@yahoo.co.in |
| Dr. BS Rao |
Tata main Hospital, Department of Medicine, Jamshedpur, Jharkhand |
,-831001
|
91 657 2430538
dr_bsrao@tatasteel.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 13 |
| Name of Committee |
Approval Status |
| Comite National D’Ethique pour la Recherche en Sante, Senegal |
Approved |
| Comite National dEthique et de Recherche (CNER) de Côte dIvoire |
Approved |
| Convite nacional De Bioetica Para A Saude, Mozambique |
Approved |
| DEthique De La FMPOS, Mali |
Approved |
| Ecole De sante publique Convite D Ethique DR Congo |
Approved |
| Ethical Review Committee, Chittagong Medical College, Bangladesh |
Approved |
| Ethics Committee of Faculty of Tropical medicine Mahidol University, Thailand |
Approved |
| Institutional Ethics Committee for Tata Main Hospital, Jamshedpur |
Approved |
| Institutional Ethics Committee, CWS Hospital, Jagda, Rourkela-769042 |
Approved |
| Institutional Ethics Committee, Ispat General Hospital, Orrisa |
Approved |
| Institutional Ethics Committee, Kasturba Medical College, Mangalore-575001 |
Approved |
| Institutional Ethics Committee, National Institute Of Malaria Research (ICMR) For Mahadevi Birla Hospital & Research Center, Ranchi |
Approved |
| Pharmacy, Medicines and Poisons Board, Malawi |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
Acute Uncomplicated Plasmodium falciparum malaria, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Coartem® tablets (each tablet containing artemether 20 mg and lumefantrine 120 mg in FDC) of Novartis for oral administration |
Six dose treatment as a single dose of four tablets at the time of initial diagnosis followed by four tablets after eight hours then four tablets twice daily (morning and evening) on each of the following days |
| Intervention |
Fixed dose combination (FDC) tablets of arterolane maleate 150 mg and PQP 750 mg of Ranbaxy Laboratories Limited, India for oral administration |
once daily for three days |
|
Inclusion Criteria
Modification(s)
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| Age From |
|
| Age To |
|
| Gender |
|
| Details |
Patients must fulfill the following inclusion criteria to be eligible for enrollment into the study:
1. M/F patients b/w age of 12 to 65 (Both incusive)
2. B/w more than or equal to 35 kg at screening
3. presence of acute symptomatic uncomplicated malaria with confirmed diagnosis by blood smear with asexual forms of P. falciparum parasites only.
4. asexual parasites/µL in blood in patients b/w 1,000 and 100,000 (both inclusive)
5. presence of fever (axillary temperature ≥ 37.5 °C or oral ≥ 38 °C) or a documented history of fever in the past 24 hours
6. Female patients, if of child-bearing potential must be non-lactating and willing to use contraceptive methods during the study period
7. Written informed consent, provided by patient in accordance with local practice. If a patient is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least one witness is acceptable. For adolescents written informed consent, in accordance with local practice, provided by parent/guardian. If the parent/guardian is unable to write, thumb print witnessed consent is permitted. For patients < 18 yrs, wherever feasible, assent will also be obtained
|
|
| ExclusionCriteria |
| Details |
If any of the following conditions apply, the patient should not be enrolled in the study.
1. Patients with severe malaria as per WHO criteria1 (Appendix B).
2. Mixed infection with another Plasmodium species at the time of presentation (including P. vivax, P. ovale and P. malariae).
3. Hemoglobin (Hb) level of 8 gm/dL.
4. A female patient who is lactating or pregnant at screening.
5. Known allergy to artesunate, artemether, artemisinin derived products, lumefanterine, piperaquine or any other related drug.
6. Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to screening).
7. Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the World Health Organization (WHO) list of essential drugs.
8. Any antimalarial treatment during 1 month prior to screening, as assessed by medical history.
9. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carini pneumonia in children born to HIV+ women.
10. Participation in any investigational drug study during the 30 days prior to screening.
11. Any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease).
12. Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management. These abnormalities include QTc interval 450 msec at screening and cardiac conduction disorders, with the exception of right bundle branch block.
13. Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at screening:
Serum creatinine 1.5 × upper limit of normal (ULN)
Aspartate transaminase 2.5 × ULN
Alanine transaminase 2.5 × ULN
Serum bilirubin 3 mg/dL
14. Patients who have had a splenectomy as confirmed by history or clinical examination.
15. Patients with known history of human immunodeficiency virus (HIV) infection or other immunosuppressive disorders.
16. Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) that may compromise the diagnosis and the evaluation of the response to the study medication.
17. Patients who have epilepsy or a history of convulsions.
|
|
Method of Generating Random Sequence
Modification(s)
|
Permuted block randomization, fixed |
Method of Concealment
Modification(s)
|
Centralized |
Blinding/Masking
Modification(s)
|
Double Blind Double Dummy |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Proportion of patients with PCR corrected ACPR |
On Day 28 |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Parasite Clearance Time (PCT) |
Time in hours from initiation of therapy until first of the two consecutive negative smears are obtained |
| Fever Clearance Time (FCT) |
time from first dosing to first normal reading of temperature (37.5 C) for 2 consecutive normal temperature readings and a confirmed normal temperature 24 hours after the first normal body temperature reading |
| Proportion of patients with PCR-uncorrected ACPR |
Day 28 |
| Proportion of patients with PCR-uncorrected ACPR |
Day 42 |
| Proportion of patients with PCR corrected ACPR |
Day 42 |
| Proportion of aparasitemic patients |
Days 1, 2 and 3 |
| Number of gametocytes |
Days 0,1,2,3,7,14,21,28,35 and 42 |
| safety endpoints: Incidence of adverse events, lab parameters, physical examination, ECG or vitals |
Days 0,1,2,3,7,14,21,28,35 and 42 |
| Pk parameters: Cmax, Tmax, AUC, CL/F, Vd/F, t1/2 and additional PK model dependant parameter |
Days 0,1,2,7,14,21,28,35 and 42 |
|
Target Sample Size
Modification(s)
|
Total Sample Size="1200"
Sample Size from India="202"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 3/ Phase 4 |
Date of First Enrollment (India)
Modification(s)
|
20/11/2009 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
09/11/2009 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
not yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This multicenter, double blind, Phase III study (R11160083002) to compare fixed dose combination of arterolane maleate (150 mg) and PQP (750 mg) with Coartem® in adult malaria patients is ongoing.A total of 327 patients had completed the trial at 7 sites: Bangkok, Thailand; India (Ranchi, Rourkela -2 sites, Jamshedpur and Mangalore) Bandarban, Bangladesh. Six new sites has been initiated in Africa: Ivory Coast, Senegal, Mali, DRC (2 Sites), Mozambique. A total of 350 patients have been enrolled in Africa till date (17.05.2012)
|