CALINA: 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
Study Details
Study Description
Brief Summary
This study aims 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: artemether lumefantrine (2.5 mg:30 mg) artemether lumefantrine (2.5 mg:30 mg) bid over 3 days, from 1-4 tablets per dose |
Drug: artemether:lumefantrine (2.5 mg:30 mg)
artemether:lumefantrine (2.5 mg:30 mg)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Artemether Cmax [Day 1]
ART Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose)
Secondary Outcome Measures
- Lumefantrine Day 8 concentration (C168h) [168h post first dose]
- Artemether AUC [Up to Day 15 post first dose]
- DHA AUC [Up to Day 15 post first dose]
- Lumefantrine Cmax [Up to Day 8 post first dose]
- Lumefantrine AUC [Up to Day 15 post first dose]
derived as appropriate
- Parasite Clearance Time (PCT) [Up to Day 8]
Parasite count will be performed by microscopy
- Fever clearance Times (FCT) [Up to Day 8]
Body temperature will be recorded
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 15]
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 15
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 43]
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 43
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 29]
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
- Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 8]
Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 8
- Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 15]
Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15
- Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 29]
Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
- Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 43]
Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 43
- Incidence rate of recrudescence and new infections [Up to Day 43]
Incidence rate of recrudescence and new infections at Days 15, 29 and 43
- Incidence rate of serious adverse events [during the study period from Baseline up to age 365 days]
safety by collecting serious adverse events (SAEs)
- Incidence rate of adverse events [during the study period from Baseline up to day 43]
safety and tolerability by collecting adverse events (AEs)
- Incidence rate of abnormal laboratory values [during the study period from Baseline up to day 43]
Safety and tolerability by collecting routine safety laboratory assessments
- Change in head circumference [at Baseline and at age 365 days]
Head circumference will be measured
- Neurodevelopmental assessment [At Day 4 and at age 365 days]
Neurodevelopmental assessment (Shoklo Malaria Research Unit assessment) score will be derived
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female neonates/infants
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Body weight <5 kg but ≥ 2 kg
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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)
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Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections):
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in Cohort 1 of ≥500 and <100,000 parasites/µL asexual P. falciparum parasitemia
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in Cohort 2 of ≥100 and <100,000 parasites/µL asexual P. falciparum parasitemia
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in Cohort 2, either congenital or neonatal
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either symptomatic or asymptomatic
Exclusion Criteria:
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Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)
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Presence of severe malaria (according to WHO 2015 definition)
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HIV status :
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in Cohort 1, patient's or patient's mother's current treatment with ARV
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in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV
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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)
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Presence of any clinically significant neurological condition:
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any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)
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known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)
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Presence of clinically significant abnormality of the hepatic and renal systems
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Patients unable to swallow or whose drinking is impaired
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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
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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
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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
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Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
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Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
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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)
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Novartis Investigative Site | Nanoro | Burkina Faso | ||
2 | Novartis Investigative Site | Ouagadougou | Burkina Faso | ||
3 | Novartis Investigative Site | Kisantu | Bas Kongo | Congo, The Democratic Republic of the | |
4 | Novartis Investigative Site | Sotuba | Mali |
Sponsors and Collaborators
- Novartis Pharmaceuticals
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Medicines for Malaria Venture (MMV), Switzerland
- Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso
- Institut de Recherche en sciences de la Santé - Unité de Recherche Clinique de Nanoro (IRSS-URCN), Burkina Faso
Investigators
- Principal Investigator: Alfred Tiono, Groupement de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso
- Principal Investigator: Halidou Tinto, Unité de Recherche Clinique, CMA St Camille, Nanoro, Burkina Faso
- Principal Investigator: Bernhards Ogutu, Kondele Children Hospital, Kisumu , Kenya
- Principal Investigator: Issaka Sagara, MRTC, Univ. of Science, Techniques and Technology, Bamako, Mali
- Principal Investigator: Martin Meremikwu, Department of Paediatrics, University of Calabar, Calabar, Nigeria
- Principal Investigator: Gildas Wounounou, Hôpital Général de Référence St Luc, Kisantu, DR Congo
- Principal Investigator: Christine Manyando, St Pauls Mission Hospital, Nchelenge, Zambia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CCOA566B2307