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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 November 2016
• Main ID: NCT01992900
• Date of registration: 11/11/2013
• Prospective Registration: No
• Primary sponsor: sigma-tau i.f.r. S.p.A.
• Public title: A Pharmacokinetic/Pharmacodynamic Study of Eurartesim Dispersible Formulation in Infants With P.Falciparum Malaria
• Scientific title: A Phase II, Open-label, Multicentre, Pharmacokinetic, Pharmacodynamics and Safety Study of a New Paediatric Eurartesim Dispersible Formulation and Crushed Film Coated Eurartesim Tablet, in Infant Patients With P. Falciparum Malaria
• Date of first enrolment: November 2013
• Target sample size: 300
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01992900
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Burkina Faso, Congo, The Democratic Republic of the, Gambia, Mozambique, Tanzania

Contacts

• Name: Enrique O Bassat, MD
• Affiliation: Manica's health Research Centre, centre de investigacao Saude-Manica (CISM)

Key inclusion & exclusion 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.



Age minimum: 6 Months
Age maximum: 12 Months
Gender: Both

Health Condition(s) or Problem(s) studied

Malaria,Falciparum

Intervention(s)

Drug: Eurartesim dispersible oral tablet

Drug: eurartesim film coated tablet

Primary Outcome(s)

Comparison of peak plasma concentration of Dihydroartemisinin in the two studied formulations [Time Frame: DHA plasma samples will be collected on the first day of study drug administration at 20, 30, 40, 60, 100, 200 and 300 minutes post-dose]

Comparison of area under the plasma concentration versus time curve of Dihydroartemisinin in the two studied formulations. [Time Frame: DHA plasma samples will be collected on the first day of study drug administration at 20, 30, 40, 60, 100, 200 and 300 minutes post-dose]

Comparison of peak plasma concentration of Piperaquine in the two studied formulations [Time Frame: PQP plasma samples will be collected on day 0 of treatment at 40, 80, 280, 720 minutes, then on day 1 at 24 hours and on day 2 at 40, 80, 280, 720 minutes after the last drug administration and then 24, 120, 288 and 456 hours]

Comparison of area under the plasma concentration versus time curve of Piperaquine in the two studied formulations. [Time Frame: PQP plasma samples will be collected on day 0 of treatment at 40, 80, 280, 720 minutes, then on day 1 at 24 hours and on day 2 at 40, 80, 280, 720 minutes after the last drug administration and then 24, 120, 288 and 456 hours]

Secondary Outcome(s)

Blood chemistry: proportion of patients with deterioration of parameters at day 7 respect to screening. [Time Frame: screening and Day 7]

Adverse Events occurrence to calculate percentage of patients experiencing Adverse Events and Serious Adverse Events [Time Frame: during all the study period from randomization and up to day 42]

Fever clearance time [Time Frame: At screening and then about every 12 hours until the time on which body temperature falls down below 37.5 °C, or up to three days]

Hematology: proportion of patients with deterioration of parameters at day 7 respect to screening [Time Frame: screening and day 7]

Parasite clearance time [Time Frame: At screening and then about every 12 hours until the time of the first negative result, then confirmed by a second negative result or up to three days]

Change from baseline of electrocardiographic QT interval at 4-6 hours after the last study drug intake [Time Frame: Before randomization and then at 4-6 hours after the last dose of study drug.]

Secondary ID(s)

ST3073-ST3074-DM-12-002

2013-002255-15

Source(s) of Monetary Support

Please refer to primary and secondary sponsors