Plasmodium Falciparum Malaria MedDRA version: 20.0 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: PT Classification code 10035500 Term: Plasmodium falciparum infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 21.1 Level: LLT Classification code 10016171 Term: Falciparum malaria System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Artemether:Lumefantrine
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: Artemether
CAS Number: 71963-77-4
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female neonates/infants 2) Body weight 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 =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the key PK parameter of artemether in infants and neonates < 5 kg body weight dosed with the new formulation of artemether-lumefantrine dispersible tablet;Secondary Objective: -To assess other key PK parameters of artemether, DHA and lumefantrine in infants and neonates <5 kg body weight dosed with the new formulation of artemether-lumefantrine dispersible tablet -To evaluate the safety and tolerability of the new formulation of artemether-lumefantrine dispersible tablet in infants and neonates <5 kg body weight with acute uncomplicated P. falciparum malaria -To determine the efficacy of the new formulation of artemether-lumefantrine dispersible tablet for treatment of acute uncomplicated P. falciparum malaria in infants and neonates <5 kg body weight;Primary end point(s): ART Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose);Timepoint(s) of evaluation of this end point: ART Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Lumefantrine Day 8 concentration (C168h) - 168h post first dose 2) Artemether AUC: Up to Day 15 post first dose 3) DHA AUC: Up to Day 15 post first dose 4) Lumefantrine Cmax: Up to Day 8 post first dose 5) Lumefantrine AUC: Up to Day 15 post first dose 6) Parasite Clearance Time (PCT): Up to Day 8 7) Fever clearance Times (FCT): Up to Day 8 8) PCR-corrected Adequate Clinical and Parasitological Response (ACPR): Day 15, 29, 43 9) Uncorrected Adequate Clinical and Parasitological Response (ACPR): Day 8, 15, 29, 43 10) Incidence rate of recrudescence and new infections: Up to Day 43 11) Incidence rate of serious adverse events: during the study period from Baseline up to age 365 days 12) Incidence rate of adverse events: during the study period from Baseline up to day 43 13) Incidence rate of abnormal laboratory values: during the study period from Baseline up to day 43 14) Change in head circumference: at Baseline and at age 365 days 15) Neurodevelopmental assessment: At Day 4 and at age 365 days;Timepoint(s) of evaluation of this end point: 1) 168h post first dose 2) Up to Day 15 post first dose 3) Up to Day 15 post first dose 4) Up to Day 8 post first dose 5) Up to Day 15 post first dose 6) Up to Day 8 7) Up to Day 8 8) Day 15, 29, 43 9) Day 8, 15, 29, 43 10) Up to Day 43 11) during the study period from Baseline up to age 365 days 12) during the study period from Baseline up to day 43 13) during the study period from Baseline up to day 43 14) at Baseline and at age 365 days 15) at Day 4 and at age 365 days | — |
Countries
Burkina Faso, Congo, The Democratic Republic of the
Contacts
Public ContactClinical Disclosure Office
Novartis Pharma AG
Outcome results
None listed