Phase 3 trial with dispersible arterolane maleate and PQP tablets in pediatric malaria patients

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/07/004764
• Date of registration: 25-07-2014
• Prospective Registration: Yes
• Primary sponsor: Sun Pharmaceutical Industries Ltd
• Public title: Phase 3 trial with dispersible arterolane maleate and PQP tablets in pediatric malaria patients
• Scientific title: A Phase 3 open label randomized multicenter trial to assess the efficacy and safety of the dispersible arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg tablets in comparison with Coartem dispersible in pediatric patients with acute uncomplicated Plasmodium falciparum malaria
• Date of first enrolment: 08-08-2015
• Target sample size: 840
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7539
• Study type: Interventional
• Study design: Randomized, Parallel Group, Active Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:An Open list of random numbers Blinding and masking:Open Label
• Phase: Phase 3

Countries of recruitment

Cote d'Ivoire, Democratic Republic of the Congo, India, Malawi, Mali, Mozambique, Rwanda, Senegal

Contacts

• Name: Dr Sanjay K Sharma
• Affiliation: Sun Pharmaceutical Industries Ltd

• Name: Dr Rajinder K Jalali
• Affiliation: Sun Pharmaceutical Industries Ltd

Key inclusion & exclusion criteria

Inclusion criteria: Patients must fulfil the following inclusion criteria to be eligible for enrolment into the study:

1.Children of either gender (male or female) aged between 6 months to 12 years, both inclusive.

2.Minimum body weight of 5 kg.

3.Able to take drugs under study by the oral route

4.Absence of severe malnutrition (defined as a child who has symmetrical oedema involving at least the feet and whose weight-for-height is below -3 standard deviation or less than 70% of the median of the NCHS/ WHO normalized reference values or mid-upper arm circumference < 110 mm)

5.Minimum Hemoglobin (Hb) level of > 8 gm/dL.

6.Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only.

7.Initial parasite densities appropriate for inclusion will be between 1,000 and 100,000 asexual parasites/μL blood (both inclusive).

8.Presence of fever (axillary temperature >= 37.5 °C) or a history of fever in the past 24 hours.

9.Written informed consent, provided by parent/guardian. If parent/guardian is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least one witness is acceptable.

10.Willingness and ability to comply with the study protocol for the duration of the study.

11.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.


Exclusion criteria: If any of the following conditions apply, the patient should not be enrolled in the study.

1.Known allergy to artesunate, artemether, artemisinin derived products, piperaquine or any other related drug.

2.Infants with a history of hyperbilirubinemia during the neonatal period.

3.Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the World Health Organization (WHO) list of essential drugs.

4.Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae).

5.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).

6.Patients with severe malaria as per WHO criteria.

7.Presence of general danger signs of severe malaria among children 5 years old (as per WHO).

8.Female patients between the age group of 8 to 12 years (both inclusive) who are pregnant at screening. The selection of the candidate for pregnancy screening test would be as per the judgment of the Investigator.

9.Female patients between the age group of 8 to 12 years who are lactating at the time of screening.

10.Any antimalarial treatment during 1 month prior to screening, as assessed by medical history.

11.Participation in any investigational drug study during the 30 days prior to screening.

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.Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhoea 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).

14.Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at screening:

Serum creatinine 1.5Ã?upper limit of normal (ULN).

Aspartate transaminase 2.5 Ã? ULN.

Alanine transaminase 2.5 Ã? ULN.

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).

18.Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprolol, imipramine, amitriptyline, clomipramine, etc)

19.With known disturbances of electrolyte balance at screening:

Serum potassium LLN

Serum Sodium LLN



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- acute uncomplicated P.falciparum malaria in pediatric patients

Intervention(s)

Intervention1: FDC of arterolane maleate and piperaquine phosphate dispersible formulation: Arterolane maleate 37.5 mg and piperaquine phosphate 187.5 mg

Investigational drug product will be administered orally as a single daily dose for 3 consecutive days. Number (No.) of tablets in a single dose will be provided according to the following age category of the patients.
6 months to 2yrs :1 tablet;
2 yrs to 6yrs :2 tablets;
6 yrs to â?¤12yrs:3 tablets

Control Intervention1: Coartem Dispersible tablets: Coartem® dispersible (artemether 20mg and lumefantrine 120mg)
A 3-day treatment schedule with a total of 6 oral doses will be given to patients randomized to Coartem® dispersible (artemether 20mg and lumefantrine 120mg) regimen according to the following bodyweight category of the patients:
5 to 15kg : 1 tablet;
15 to 25kg : 2 tablets;
25 to 35kg : 3 tablets

Primary Outcome(s)

Day 28 PCR corrected ACPRTimepoint: Day 28 PCR corrected ACPR

Secondary Outcome(s)

â?¢Median parasite clearance time (time to reach 100% clearance) (PCT).

â?¢Fever clearance time (FCT).

â?¢Proportion of patients with PCR-uncorrected ACPR on Day 28 and Day 42.

â?¢Safety endpoints: Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, or vital signs.

Timepoint: parasitology and body temperature at 6 hour intervals, discharge/ Day 3, on follow-up Days 7 (±1), 14(±1), 28(±1) and 42(±1)

Laboratory assessment Day 2, Day 28(±1) and Day 42(±1)

ECG screening, and Day 2 between 2 and 4 hrs

Vital signs Days 1, 2, 3, 7(±1), 14(±1), 28(±1) and 42(±1)

Secondary ID(s)

R2012005, version 2, dated April 02, 2013

Source(s) of Monetary Support

Sun Pharmaceutical Industries Ltd. Plot No 20 Sector 18 Udyog Vihar Industrial Area Gurgaon 122015 Haryana

Ethics review

Status: Approved
Approval date: 23/08/2013
Contact:

Ministere de lenseignement Superieur Et De La Recherche Scientifique Mali

Status: Approved
Approval date: 29/08/2013
Contact:

Institutional Ethics Committee for Human Research of Medical College, Kolkata

Status: Approved
Approval date: 20/09/2013
Contact:

Ecole de Sante Publique Comite D Ethique DRC

Status: Approved
Approval date: 24/09/2013
Contact:

Republique Du Senegal Ministere De La Sante Et De La Prevention Direction De la Sante Dakar senegal

Status: Approved
Approval date: 12/11/2013
Contact:

Institutional Ethics Committee, Calcutta School of Tropical Medicines, Kolkata

Status: Approved
Approval date: 15/11/2013
Contact:

Institutional Ethics Committee of Kalinga Institute of Medical Sciences (KIMS) Bhubaneswar

Status: Approved
Approval date: 09/12/2013
Contact:

Institutional Ethics Committee Seth GS medical College & KEM hospital Mumbai

Status: Approved
Approval date: 13/12/2013
Contact:

National Health Sciences Research Committee Malawi

Status: Approved
Approval date: 21/01/2014
Contact:

Pentamed Ethics Committee, Medipoint Hospital Pune

Status: Approved
Approval date: 12/03/2014
Contact:

Institutional Ethics Committee, AJMC, Mangalore

Status: Approved
Approval date: 02/04/2014
Contact:

Institutional Ethics Committee, KGH, Visakhapatnam

Status: Approved
Approval date: 06/06/2014
Contact:

Ethics Committee Centre Hospitlier Universtaire University Teaching Hospital Kigali Rwanda

Status: Approved
Approval date: 12/06/2014
Contact:

Comite D Ethique de la FMPOS, Mali

Status: Approved
Approval date: 14/07/2014
Contact:

Comite National Dethique Et De La Recherche Ivory Coast

Status: Approved
Approval date: 08/08/2014
Contact:

Comite D Ethique KUTH for Gakurazo Health center Rwanda

Status: Approved
Approval date: 16/08/2014
Contact:

Ethics Committee St Theresas Hospital, Hyderabad

Status: Approved
Approval date: 28/10/2014
Contact:

Ecole de Sante Publique Comite D Ethique DRC for kinshasa site

Status: Approved
Approval date: 30/10/2014
Contact:

Ethics Cimmittee for Human Research LHMC and associated Hospitals new delhi

Status: Approved
Approval date: 11/11/2014
Contact:

Institutional Ethisc Committee BJMC Pune

Status: Approved
Approval date: 02/02/2015
Contact:

Institutional Ethics Comittee, IGH, Rourkela

Status: Approved
Approval date: 08/05/2015
Contact:

Ethics Committee AIIMS, Bhubaneswar

Status: Approved
Approval date: 24/08/2015
Contact:

Institutional Ethics Committee

Status: Approved
Approval date: 08/09/2015
Contact:

Institutional Ethics Comittee

Status: Approved
Approval date: 22/09/2015
Contact:

Institutional Ethics Committee ICH

Results

• Date Completed: 27/01/2016