A Pharmacokinetic/Pharmacodynamic Study of Eurartesim Dispersible Formulation in Infants With P.Falciparum Malaria

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

There is a need for paediatric formulations that permit accurate dosing and enhance patient compliance. However, for the treatment of malaria, scarce paediatric-friendly formulations are available on the market. Thus, a new water dispersible formulation of eurartesim has been developed for oral administration.

Aim of this study is to provide data on pharmacokinetic profile, safety and efficacy of this new paediatric formulation and compare it with the crushed film coated tablet in infant patients (6 to ≤12 months of age) suffering from uncomplicated Plasmodium falciparum malaria.

Furthermore, a Pharmacokinetic/Pharmacodynamic(PK/PD) modelling will be built up to establish PK/PD relationship in adult and paediatric populations.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: sigma-tau i.f.r. S.p.A.
• Treatments: Artemisinins; Artenimol; Dihydroartemisinin; Piperaquine

Criteria

Inclusion Criteria:

• Male and Female infants aged from 6 months to ≤ 12 months included.

• Ability to swallow oral suspension.

• Body weight >5 kg.

• Uncomplicated malaria, with microscopically confirmed mono-infection by P. falciparum (parasitaemia ≥1000/microL and <200000/microL).

• History of fever anytime during the preceding 48 hours or presence of fever (axillary temperature ≥37.5 °C or ≥38.0 °C rectally).

• Ability of parents or guardians to understand the nature of the trial and providing signed informed consent.

• Stable residence in the study area during the two months after recruitment and willingness to comply with the study protocol and the study visit schedule.

Exclusion Criteria:

• Antimalarial treatment with amodiaquine, chloroquine, quinine or lumefantrine-based compounds within the previous 6 weeks, with piperaquine-based compound, or mefloquine, or sulphadoxine pyrimethamine within the previous 3 months and with halofantrine within the 30 days prior to screening.

• Any other antimalarial treatment or antibiotics with antimalarial activity (including cotrimoxazol) and any herbal products, within the 7 days prior to screening.

• Severe malnutrition (defined as weight for height <70% of the median National Center for Health Statistics(NCHS)/WHO reference).

• Severe vomiting or dehydration.

• Presence of jaundice.

• Known hypersensitivity to the artemisinin-based therapy or piperaquine.

• History of relevant clinical allergic reaction of any origin.

• Clinical and/or laboratory features of severe malaria.

• Known moderate/ severe renal or liver insufficiency.

• Evidence of clinically relevant haematological, pulmonary, metabolic-endocrine, neurological, urogenital diseases as judged by the investigator.

• Already diagnosed HIV infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

• Previous admission for, or evidence of symptomatic cardiac arrhythmias or with clinically relevant bradycardia at screening (bpm < 90).

• Family history of sudden death, or known congenital prolongation of the QT interval, or any clinical condition known to prolong the QT interval.

• ECG abnormality that requires urgent management.

• Any treatment which can induce a lengthening of QT interval.

• Gastrointestinal dysfunction that could alter absorption or motility (i.e. malabsorption syndromes, intestinal sub-occlusion or previous major gastrointestinal surgery).

• Any contraindication to blood sampling.

• Moderate and severe anaemia (Hb < 7 g/dL).

• Patients who have used any drugs or substances known to be strong inhibitors of Cytochrome P enzymes (formerly known as cytochrome P450 enzymes) within 10 days prior to screening.

• Patients who have used any drugs or substances known to be strong inducers of CYP enzymes (formerly known as cytochrome P450 enzymes)within 28 days prior to screening.

• Children lactated by HIV positive women who are undergoing treatment with antiretroviral drugs.

• Participation in any investigational drug study during the 30 days prior to screening or previously randomised in the present trial.