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 (CALINA)

Phase 1

• Conditions: Plasmodium Falciparum Malaria; MedDRA version: 20.0Level: SOCClassification code 10021881Term: Infections and infestationsSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1Level: PTClassification code 10035500Term: Plasmodium falciparum infectionSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 21.1Level: LLTClassification code 10016171Term: Falciparum malariaSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

• Registration Number: EUCTR2023-000804-21-Outside-EU/EEA
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-29
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1) Male or female neonates/infants
2) Body weight <5 kg but = 2 kg
3) 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)
4) 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
in Cohort 2, either congenital or neonatal
either symptomatic or asymptomatic
Are the trial subjects under 18? yes
Number of subjects for this age range: 22
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1) Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)
2) Presence of severe malaria (according to WHO 2015 definition)
3) 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
4) 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)
5) 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)
6) Presence of clinically significant abnormality of the hepatic and renal systems
7) Patients unable to swallow or whose drinking is impaired
8) 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
9) 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
10) 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
11) Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
12) Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
13) Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug (see Table 6-2)
14) Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified