Pharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria

NCT04300309 | Terminated Phase 2 Results DMC

• 2 other identifiers: CCOA566B2307PACTR202004535453508
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this study was to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants \<5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.

Conditions

Plasmodium Falciparum Malaria

Keywords

Plasmodium falciparum; malaria; artemether; lumefantrine; neonates; infants

Outcome Measures

Primary Outcomes (1)

• Artemether Cmax After First Dose

  Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations.

  1 and 2 hours after first dose (Day 1)

Secondary Outcomes (12)

• Lumefantrine Day 8 Concentration (C168h)

  168 hours after first dose (corresponding to 108 hours after last dose)

• Lumefantrine Cmax After Last Dose

  62, 66, 68 and 84 hours after first dose (corresponding to 2, 6, 8 and 24 hours after last dose)

• DHA Cmax After First Dose

  1 and 2 hours after first dose (Day 1)

• Parasite Clearance Time (PCT)

  Up to 48 hours after first dose

• Fever Clearance Times (FCT)

  Up to 36 hours after first dose

Study Arms (1)

artemether lumefantrine (2.5 mg:30 mg)

EXPERIMENTAL

Artemether-lumefantrine (5 mg:60 mg) twice daily for 3 days

Drug: artemether:lumefantrine (2.5 mg:30 mg)

Interventions

artemether:lumefantrine (2.5 mg:30 mg) DRUG

Two oral dispersible tablets twice daily for three consecutive days. Each tablet contained artemether-lumefantrine 2.5 mg:30 mg.

artemether lumefantrine (2.5 mg:30 mg)

Eligibility Criteria

• Age: Up to 365 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female neonates/infants
• Body weight \<5 kg but ≥ 2 kg
• In Cohort 1, infants aged \>28 days; in Cohort 2, neonates aged 1 to ≤28 days (3 subgroups: 1-7 days; 8-14 days; 15-28 days)
• Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections):
• in Cohort 1 of ≥500 and \<100,000 parasites/µL asexual P. falciparum parasitemia
• in Cohort 2 of ≥100 and \<100,000 parasites/µL asexual P. falciparum parasitemia
• either congenital or neonatal
• either symptomatic or asymptomatic

You may not qualify if:

• Head circumference \< - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)
• Presence of severe malaria (according to WHO 2015 definition)
• HIV status :
• in Cohort 1, patient's or patient's mother's current treatment with ARV
• in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV
• Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants) (WHO 2005)
• Presence of any clinically significant neurological condition:
• any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)
• known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)
• Presence of clinically significant abnormality of the hepatic and renal systems
• Patients unable to swallow or whose drinking is impaired
• Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes
• History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion
• Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
• Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Medicines for Malaria Venture: collaborator
• Groupe de Recherche Action en Sante: collaborator
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator

Study Sites (3)

Novartis Investigative Site

Nanoro, Burkina Faso

Location

Novartis Investigative Site

Ouagadougou, Burkina Faso

Location

Novartis Investigative Site

Kisantu, Bas Kongo, Democratic Republic of the Congo

Location

Related Publications (1)

• Wounounou G, Tiono AB, Ogutu B, Manyando C, Sagara I, Schneitter S, Bassat Q, Gaaloul ME, Marrast AC, Demin I, Winnips C, Risterucci C, Hugot S, Hofstetter G, Qian Z, Su G, Zhang J, Renner KC, Cousin M, Venishetty VK, Sayyed S, Gandhi P, Kabore B; CALINA study group. Pharmacokinetics, safety and efficacy of an optimized dose of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in neonates and infants of less than 5 kg body weight: a multicentre, open-label, single-arm phase 2/3 study (CALINA). Trop Med Health. 2025 Nov 6;53(1):151. doi: 10.1186/s41182-025-00828-z.

  PMID: 41199347 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com
• A Pediatric Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: March 9, 2020
• Study Start: December 21, 2020
• Primary Completion: July 2, 2023
• Study Completion: May 10, 2024
• Last Updated: January 13, 2026
• Results First Posted: October 3, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

BU (2); DE (1)