Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.

Abstract

BACKGROUND:

Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children.

METHODS:

This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days.

RESULTS:

The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar.

CONCLUSIONS:

The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients.

CLINICAL TRIALS REGISTRATION:

CTRI/2014/07/004764.

• Authors: Offianan Andre Toure, Victor Mwapasa, Issaka Sagara, Oumar Gaye, Ricardo Thompson, Aishwarya V Maheshwar, Pitabas Mishra, Narendra Behra, Antoinette K Tshefu, Rashmi R Das, Anupkumar R Anvikar, Pradeep Sharma, Arjun Roy, Sanjay K Sharma, Amit Nasa, Rajinder K Jalali, Neena Valecha, Arterolane Maleate-Piperaquine Phosphate (AM-PQP) Study Team
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 65 Issue 10 Pg. 1711-1720 (Oct 30 2017) ISSN: 1537-6591 [Electronic] United States
• PMID: 29020247 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Antimalarials
• Artemether, Lumefantrine Drug Combination
• Artemisinins
• Drug Combinations
• Ethanolamines
• Fluorenes
• Heterocyclic Compounds, 1-Ring
• Peroxides
• Quinolines
• Spiro Compounds
• Tablets
• arterolane
• piperaquine

Topics

• Africa
• Antimalarials (adverse effects, blood, pharmacokinetics, therapeutic use)
• Artemether, Lumefantrine Drug Combination
• Artemisinins (adverse effects, blood, pharmacokinetics, therapeutic use)
• Child
• Child, Preschool
• Drug Combinations
• Ethanolamines (adverse effects, blood, pharmacokinetics, therapeutic use)
• Female
• Fluorenes (adverse effects, blood, pharmacokinetics, therapeutic use)
• Heterocyclic Compounds, 1-Ring (adverse effects, blood, pharmacokinetics, therapeutic use)
• Humans
• India
• Infant
• Malaria, Falciparum (drug therapy, mortality)
• Male
• Peroxides (adverse effects, blood, pharmacokinetics, therapeutic use)
• Quinolines (adverse effects, blood, pharmacokinetics, therapeutic use)
• Spiro Compounds (adverse effects, blood, pharmacokinetics, therapeutic use)
• Survival Analysis
• Tablets