| CTRI Number |
CTRI/2011/11/002129 [Registered on: 15/11/2011] Trial Registered Retrospectively |
| Last Modified On: |
21/02/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Phase III trial of FDC of arterolane maleate and PQP tablets in patients with acute uncomplicated Plasmodium vivax malaria |
|
Scientific Title of Study
|
A phase III, open label, randomized, parallel group, multicentric trial comparing the safety and efficacy of fixed dose combination tablets of arterolane maleate and piperaquine phosphate (PQP) with chloroquine tablets in patients with acute uncomplicated Plasmodium vivax malaria |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| R2011005 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Nilanjan Saha |
| Designation |
Vice President Clinical Pharmacology & Development |
| Affiliation |
Ranbaxy Laboratories Limited |
| Address |
Medical Affairs & Clinical Research
77-B IFFCO Road
Sector 18
Udyog Vihar Industrial Area Gurgaon
Gurgaon
HARYANA
122015
India |
| Phone |
911244194340 |
| Fax |
911244016855 |
| Email |
nilanjan.saha@ranbaxy.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Sanjukta Bhattacharyya |
| Designation |
Group Leader |
| Affiliation |
Ranbaxy Laboratories Limited |
| Address |
Medical Affairs & Clinical Research
77-B IFFCO Road
Sector 18
Udyog Vihar Industrial Area Gurgaon
Gurgaon
HARYANA
122015
India |
| Phone |
911244194255 |
| Fax |
911244016855 |
| Email |
sanjukta.bhattacharyya@ranbaxy.com |
|
Details of Contact Person
Public Query
|
| Name |
Sanjukta Bhattacharyya |
| Designation |
Group Leader |
| Affiliation |
Ranbaxy Laboratories Limited |
| Address |
Medical Affairs & Clinical Research
77-B IFFCO Road
Sector 18
Udyog Vihar Industrial Area Gurgaon
Gurgaon
HARYANA
122015
India |
| Phone |
911244194255 |
| Fax |
911244016855 |
| Email |
sanjukta.bhattacharyya@ranbaxy.com |
|
|
Source of Monetary or Material Support
|
| Ranbaxy Laboratories Limited |
|
|
Primary Sponsor
|
| Name |
Ranbaxy Laboratories Limited |
| Address |
77-B IFFCO Road
Sector 18
Gurgaon
Haryana INDIA |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nithya Gogtay |
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital |
New MS Building 1st Floor
Parel
Mumbai 400 012
INDIA
Mumbai
MAHARASHTRA |
912224174420
912224112871
njgogtay@hotmail.com |
| Dr G C Rajadhyaksha |
Department of Medicine, BYL Nair Charitable Hospital & TN Medical College |
Dr AL Nair Road
Mumbai Central
Mumbai - 400 008
India
Mumbai
MAHARASHTRA |
912223005690
912223005690
girishraj63@hotmail.com |
| Dr Sanjay Kumar Kochar |
Department of Medicine, SP Medical College and Associated Group of Hospitals |
Department of Medicine
SP Medical College
Bikaner - 334003 INDIA
Bikaner
RAJASTHAN |
919460128222
drskkochar@rediffmail.com |
| Dr Santanu Tripathi |
Department of Pharmacology, Calcutta School of Tropical Medicine |
Department of Pharmacology
Calcutta School of Tropical Medicine
Kolkata
India
Kolkata
WEST BENGAL |
919230566771
tripathi.santanu@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 9 |
| Name of Committee |
Approval Status |
| Canara Research Ethical Committee, Mangalore |
Approved |
| Ethics Committe SP Medical College and Associated Group of Hospitals Bikaner |
Approved |
| Ethics Committee for Research on Human Subjects Seth GS Medical College and KEM Hospital Mumbai |
Approved |
| Instituional Ethics Committee, NIMR, Delhi |
Approved |
| Institutional Ethics Committee BYL Nair Ch Hospital & TN Medical College Mumbai |
Approved |
| Institutional Ethics Committee King George Hospital, Visakhapatnam |
Approved |
| Institutional Ethics Committee School of Tropical Medicine Kolkata |
Approved |
| Institutional Ethics Committee, Ahmedabad |
Approved |
| Sumandeep Vidyapeeth Institutional Ethics Committee, Vadodara |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Acute uncomplicated Plasmodium vivax malaria, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Chloroquine tablets of Bayer |
Total 4 doses to be administered to a single patient. A total dose of 2.5 g chloroquine phosphate equivalent to 1.5 g base); each tablet containing 250 mg of chloroquine phosphate USP, equivalent to 150 mg of chloroquine base;
Second dose, Third dose and Fourth dose to be administered at 6(+2), 24(+/-4) and 48(+/-4)hrs respectively with respect to First dose administration.
To be administered by oral route over 3 consecutive days |
| Intervention |
Fixed Dose Combination(FDC) tablets of arterolane
maleate 150 mg and PQP 750 mg of Ranbaxy
Laboratories Limited, India
|
Total 3 doses to be given to patients. Single tablet of FDC of arterolane maleate 150 mg and PQP 750 mg on each consecutive day(total of 3 tablets);
Second dose and Third dose to be given 24(+/- 4)hrs and 48(+/- 4)hrs respectively with respect to the First dose administration;
To be administered by Oral route over 3 consecutive days |
|
|
Inclusion Criteria
|
| Age From |
13.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Patients must fulfill the following inclusion criteria to be eligible for enrollment into the study:
1. Body weight must be > 40 kg at screening.
2. Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. vivax parasites only.
3. Parasite density appropriate for inclusion will be > 250/ µL of blood.
4. Presence of fever (axillary temperature ≥ 37.5 °C or oral ≥ 38 °C) or history of fever in the past 48 hours.
5. Female patients, if of child-bearing potential must be non-lactating and willing to use contraceptive methods during the study period.
6. Patients willing to give informed consent. Patients <18 years, wherever feasible to the extent of the patient’s capabilities willing to provide informed assent and their parent/legal acceptable representative willing to provide informed consent.
7. Willingness and ability to comply with the study protocol for the duration of the study.
8. Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible
|
|
| 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 criteria 1, 17 (Appendix B).
2. Mixed infection with another Plasmodium species at the time of presentation (including P. falciparum, P. ovale and P. malariae).
3. Hemoglobin (Hb) level of 8 gm/dL.
4. Past history of hemolytic anaemia or methemoglobinemia.
5. A female patient who is lactating or pregnant at screening.
6. Known allergy to artesunate, artemisinin derived products, piperaquine, chloroquine, primaquine or any other related drugs.
7. 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).
8. Use of concomitant medications that may induce haemolysis or haemolytic anaemia or depressants of myeloid element of the bone marrow.
9. Any antimalarial treatment during 1 month prior to screening, as assessed by medical history.
10. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole.
11. Participation in any investigational drug study at least 3 months prior to screening.
12. 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).
13. 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.
14. Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at screening:
„X Serum creatinine 1.5 ¡Ñ upper limit of normal (ULN)
„X Aspartate transaminase 2.5 ¡Ñ ULN
„X Alanine transaminase 2.5 ¡Ñ ULN
„X Serum bilirubin 3 mg/dL
15. Patients who have had a splenectomy as confirmed by history or clinical examination.
16. Patients with known history of human immunodeficiency virus (HIV) infection or other immunosuppressive disorders.
17. 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.
18. Patients who have epilepsy or a history of convulsions.
19. Patients who are G6PD deficient indicated by laboratory investigation at screening.
20. Any retinal/ visual field defects or auditory defects, of any etiology assessed on the basis of history. .
21. Patients with psoriasis and porphyria assessed on the basis of history |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of aparasitemic and afebrile patients at 72 hours |
72 hours |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Cure rate |
Day 28 |
| Parasite clearance time (PCT) |
Hours |
| Fever clearance time (FCT) |
Hours |
|
|
Target Sample Size
|
Total Sample Size="316"
Sample Size from India="316"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
17/10/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
The proposed Phase III study is an open label, randomized, parallel group, multicentric trial comparing the safety and efficacy of FDC tablets of arterolane maleate and piperaquine phosphate with chloroquine tablets in patients with acute uncomplicated Plasmodium vivax malaria.
The study protocol (Study number: R2011005) submitted to the DCGI on 30 June 2011.
The study is planned to be initiated at 3-5 sites in India in the month of September/October 2011.
Approximately 316 patients will be enrolled into the study to provide 284 evaluable patients in 1:1 ratio (142 evaluable patients each in arterolane maleate + piperaquine and chloroquine arms).
Informed consent will be obtained from all patients before enrolling them in the study.Patients will be screened as per the inclusion/ exclusion criteria according to the study protocol and will be randomly assigned to one of the two treatment groups:
1. Fixed dose combination (FDC) tablets of arterolane maleate 150 mg and PQP 750 mg; 3 doses (total of 3 tablets) of Ranbaxy Laboratories
Limited, India for oral administration over 3 days
or
2. Chloroquine tablets (a total dose of 2.5 g chloroquine phosphate equivalent to 1.5 g base), each tablet containing 250 mg of chloroquine phosphate USP, equivalent to 150 mg of chloroquine base; 4 doses (total of 10 tablets of 250 mg each) of Bayer for oral administration over 3 days
One tablet of 26.3 mg (equivalent to 15 mg base) of primaquine phosphate of Ipca Laboratories Limited, India for oral administration will be provided to the study patients for consuming it over 14 consecutive days (one tablet/day) i.e. starting on Day 3/ Day of discharge following the 3-day treatment period as an anti-relapse measure. Medication compliance cards will be issued to all enrolled patients to monitor primaquine compliance.
The Primary objective of the study is to compare the proportion of aparasitemic and afebrile patients at 72 hours in the two treatment groups.
Patients’ participation will be for atleast 42(±2) days following the first dose of study medication. Patients will be hospitalized for at least 3 days (Days 0, 1 and 2) and will be discharged from the study site on Day 3.The patient will return to the study site for follow up visits on Days 7(±1), 14(±1), 21(±2), 28(+2), 35 (±2) and 42(±2) / end of study, or on any day if the patient spontaneously returns with fever.
Blood Sampling for Pharmacokinetic Analysis will be done as per the protocol for enrolled patients.
All AEs reported from the time of study medication administration until end of study visit i.e. Day 42 will be recorded, whether elicited or spontaneously reported by the patient. Adverse events will be evaluated by the Investigator as per CTCAE/ CTEP.
Patients who are considered to be treatment failures will be withdrawn from the study and given rescue treatment.
|