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

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2015/08/006087
• Date of registration: 12-08-2015
• Prospective Registration: Yes
• Primary sponsor: Sun Pharmaceutical Industries Limited
• Public title: Phase 3 trial with dispersible arterolane maleate and piperaquine tablets in pediatric malaria patients
• Scientific title: A Phase III, Open Label, Randomized, Multicenter, Parallel Group Trial to Assess the Efficacy and Safety of the Fixed Dose Combination of Arterolane Maleate 37.5 mg and Piperaquine Phosphate (PQP) 187.5 mg Dispersible Tablets in Comparison with Chloroquine Phosphate in Pediatric Patients with Acute Uncomplicated Plasmodium Vivax Malaria.
• Date of first enrolment: 08-09-2015
• Target sample size: 150
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=12226
• 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

India

Contacts

• Name: Dr Amit Nasa
• Affiliation: Sun Pharmaceutical Industries Ltd

• Name: Dr Sanjay Kumar Sharma
• 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 sex (male or female) aged between 6 months to 12 years (both inclusive).

2. Parent/Guardian/LAR willing to undergo audio visual recording of the consent process and provide a written informed consent by parent/guardian/LAR. If parent/guardian/LAR is unable to provide informed consent in writing, a thumbprint on informed consent document to indicate consent in the presence of at least one witness is acceptable.

3. Minimum body weight of 5 kg.

4. Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. vivax parasites >=250/ µL of blood.

5. Absence of acute severe malnutrition (defined as weight-for-height below -3 standard deviation of WHO normalized reference values and mid-upper arm circumference <115 mm)

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

7. Minimum Haemoglobin (Hb) level of >8 gm/dL.

8. Presence of fever (axillary temperature >=37.5 °C or oral >=38 °C) or a history of fever in the past 24 hours.

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


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

1. Known allergy to arterolane maleate, artesunate, artemisinin derived products, piperaquine, chloroquine, primaquine, excipients of these drugs or any other related drugs.

2. Patients with severe malaria as per WHO criteria.

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

4. Mixed infection with another Plasmodium species at the time of presentation (including P. falciparum, P. ovale and P. malariae).

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

6. Patients with history of hemolytic anaemia or methemoglobinemia.

7. Use of concomitant medications that may induce haemolysis or haemolytic anaemia or depressants of myeloid element of the bone marrow.

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

9. 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).

10. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole, doxycycline & malarone.

11. Patients with significant disease(s), disorder(s) other than malaria that in the opinion of the Investigator may (i) put the patient at risk because of participation in the study or (ii) interfere with the study evaluations or (iii) cause concern regarding patientsâ?? ability to participate in the study.

12. Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management, including 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 or electrolyte imbalance indicated by any of the following laboratory evaluations at screening:

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

• Aspartate transaminase 2.5 Ã? ULN

• Alanine transaminase 2.5 Ã? ULN

• Serum bilirubin 3 mg/dL

• Serum potassium Lower limit of Normal (LLN)

• Serum Sodium LLN

14. Patients who have had a splenectomy as confirmed by history or clinical examination.

15. Patients who are G6PD deficient indicated by laboratory investigation at screening.

16. Patients with history of any retinal/ visual field defects or auditory defects of any etiology assessed on the basis of history.

17. Patients with psoriasis and porphyria assessed on the basis of history.

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

19. Participation in any investigational drug study at least 3 months prior to screening.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Acute uncomplicated P.vivax malaria in pediatric patients

Intervention(s)

Intervention1: FDC of arterolane maleate and piperaquine phosphate dispersible oral formulation: The study drug FDC of arterolane maleate 37.5 mg + Piperaquine phosphate 187.5 mg dispersible tablet will be administered 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 2 years : 1 tab; 2 years to 6 years: 2 tabs; 6 years to 12 years: 3 tabs
Intervention2: Primaquine dispersible tablets: Dispersible tablets of primaquine phosphate equivalent to 2.5 mg base for oral administration shall be provided to the study patients. The treatment with primaquine will be continued for 14 consecutive days i.e. starting on Day 3 following the 3-day treatment period as an anti-relapse measure.
Primaquine will be administered according to he age criteria:
6 months to 1 year:Nil,
1 year to 5 years: 1 tab,
5 years to 9 years: 2 tabs,
9 years to â?¤12 years: 4 tabs
Control Intervention1: Chloroquine oral suspension or tablets: Chloroquine oral suspension contains chloroquine as 50mg/5ml for oral administration. Each chloroquine tablet contains 250 mg of chloroquine phosphate USP, equivalent to 150 mg of chloroquine base.
Chloroquine oral suspension (50mg/5ml) will be administered as single daily dose for 3 days to patients 9 years. Chloroquine tablets (Each tablet containing 250 mg of chloroquine phosphate USP, equivalent to 150 mg of chloroquine base) will be administered to patients who are â?¥9 years of age. The single dose will be provided according to the following age category of the patients.
6 months to 1 year- Day 1: 7.5 ml, Day 2 : 7.5 ml, Day 3: 3.75 ml.
1 year to 5 years- Day 1:15 ml, Day 2:15 ml, Day 3:7.5 ml.
5 years to 9 years- Day 1:30 ml, Day 2:30 ml, D

Primary Outcome(s)

Proportion of aparasitemic and afebrile patients at 72 hoursTimepoint: Proportion of aparasitemic and afebrile patients at 72 hours

Secondary Outcome(s)

Cure rate on Day 28

Parasite Clearance Time (PCT)

Fever Clearance Time (FCT)

Cure rate at Day 42

Safety endpoints: Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, vital signsTimepoint: Parasitology and body temperature at screening, predose day 0 and at 6 hour intervals, 72 hours, Day of Discharge (if patient is discharged � 6 hr post 72 hr time point), 7(±1), 14(±1), 28(±1) and 42(±1) / end of study.

Laboratory assessment at Screening, Day 2, 7(±1), 28(±1) and 42(±1).

ECG at screening, between 2 and 4 hours after the 3rd dose.

Vitals at screening, days 1, 2, 3, 7(±1), 14(±1), 28(±1) and 42(±1).

Secondary ID(s)

R2013005, Version 1.2, 1 Sep 2015

Source(s) of Monetary Support

Sun Pharmaceutical Industries Limited, Medical Affairs & Clinical Research, Sarhaul, Sector-18, Udyog Vihar Industrial Area Gurgaon 122015 Haryana

Ethics review

Status: Approved
Approval date: 18/07/2015
Contact:

Popular Hospital Ethics Committee, Varanasi

Status: Approved
Approval date: 20/07/2015
Contact:

Ethics Committee Panchsheel Hospital

Status: Approved
Approval date: 20/07/2015
Contact:

Nirmal Hospital Institutional Ethics Committee

Status: Approved
Approval date: 22/07/2015
Contact:

Institutional Ethics Committee, AJMC, Mangalore

Status: Approved
Approval date: 22/07/2015
Contact:

Marudhar Hospital Ethics Committee, Jaipur

Status: Approved
Approval date: 26/07/2015
Contact:

Institutional Ethics Committee, lucknow

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

Ethics Committee, Shalby limited, Ahmedabad

Status: Approved
Approval date: 19/08/2015
Contact:

Dr. JMSHFBMRC Institutional Ethics Committee, Ahmedabad

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

Ethics Committee Institute of Child Health, Kolkata

Status: Approved
Approval date: 06/10/2015
Contact:

Ethics Committee Sir Ganga Ram Hospital, Delhi

Status: Approved
Approval date: 09/11/2015
Contact:

Ethics Committee for Human Research, Lady Hardinge Medical College and Associated Hospitals, Delhi

Status: Approved
Approval date: 18/11/2015
Contact:

Ethics committee osmania Medical College

Status: Approved
Approval date: 04/12/2015
Contact:

Institutional Ethics Committee-LTMMC sion Mumbai

Status: Approved
Approval date: 09/01/2016
Contact:

Ethics Committee AIIMS Bhubaneswar

Status: Approved
Approval date: 17/02/2016
Contact:

Manipal university Ecthics committee Mangalore

Status: Approved
Approval date: 18/02/2016
Contact:

ASMHIEC kolhapur

Status: Approved
Approval date: 27/02/2016
Contact:

CCMMCIEC durg

Status: Approved
Approval date: 27/02/2016
Contact:

sudbhawana Hospital Ethics committee varanasi

Status: Approved
Approval date: 18/03/2016
Contact:

Institutional Ethics Committee, Seth GSMC and KEMH

Status: Approved
Approval date: 14/04/2016
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SMCHIEC Merrut

Status: Approved
Approval date: 14/04/2016
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Vintage IEC Goa

Status: Approved
Approval date: 25/04/2016
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KIMSIEC karad

Status: Not Approved
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Guru Tegh Bahadur Hospital Ethics Committee

Status: Not Approved
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Human Research Ethics Committee, Government Medical College, Surat

Status: Not Approved
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Institutional Ethics Committee , gandhi Medical College, Secunderabad

Status: Not Approved
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Institutional Ethics Committee, BJ Medical College and Civil Hospital, Ahmedabad

Status: Not Approved
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KGMC IEC Lucknow

Status: Not Approved
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sharda hospital IEC Greater Noida