A phase II study to compare a new paediatric eurartesim dispersible formulation and crushed film coated eurartesim tablet, in infant patients with Plasmodium falciparum malaria

• Register: EUCTR
• Last refreshed on: 10 November 2014
• Main ID: EUCTR2013-002255-15-Outside-EU/EEA
• Date of registration: 04/11/2014
• Prospective Registration: Yes
• Primary sponsor: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.
• Public title: A phase II study to compare a new paediatric eurartesim dispersible formulation and crushed film coated eurartesim tablet, in infant patients with Plasmodium 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 Plasmodium falciparum malaria
• Target sample size: 300
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002255-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Burkina Faso, Congo, Gambia, Mozambique, Tanzania, United Republic of

Contacts

• Name: Clinical Research Department
• Affiliation: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

• Name: Clinical Research Department
• Affiliation: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

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/?L and <200000/?L).
•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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 (SP) 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 NCHS/WHO reference).
•Severe vomiting or dehydration.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

Uncomplicated Plasmodium falciparum malaria

Intervention(s)

Product Name: Eurartesim
Pharmaceutical Form: Dispersible tablet

Primary Outcome(s)

Secondary Objective: •To evaluate the efficacy of eurartesim in treating uncomplicated malaria episodes and its ability in protecting patients from reinfections and/or recrudescence.
•To assess the PK/PD relationship of eurartesim in malaria patients.
•To evaluate safety and tolerability of eurartesim in infants.

Main Objective: To assess the PK of the eurartesim (PQP/DHA) new water dispersible formulation, film coated tablet and crushed film coated tablet in venous blood samples during and after a therapeutic course of Eurartesim in paediatric population

Primary end point(s): •To estimate the population and individual PK parameters and variability of PQ and DHA in the paediatric population when administered with eurartesim.

Timepoint(s) of evaluation of this end point: Blood samples will be collected over 72 h from eurartesim dosing during admission and then on Days 7, 14 and 21, according to the sparse blood sampling collections. The children, discharged from the clinical unit after the blood samples collection time at Day 3, will need to come back on Days 7, 14, 21, 28 and 42.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Malaria blood smear (thick and thin blood films) will be performed at the following days:
oAt screening (Day 0) and repeated in the afternoon in case of morning study drug administration (before 12:00 am),
oIn the morning and afternoon on Day 1, Day 2 (till to two consecutive negative results) and then at Day 3 before discharge, Day 7, Day 14 (±1), Day 21 (-1),Day 28 (±3) and Day 42 (?3),
oIn occasion of any PK blood drawing till Day 2 included (only thick blood film).

PCR sampling at:
oAt screening (Day 0) and subsequently from Day 7 at any scheduled or unscheduled visit within 42 days follow-up.

Secondary end point(s): •Day 28 polymerase chain reaction (PCR) corrected Adequate Clinical and Parasitological Response (ACPR).
•Day 28 Crude (PCR uncorrected) ACPR.
•Proportion of patients with early and late treatment failure.
•Asexual parasite density and clearance time (PCT).
•Fever clearance time (FCT).
•Gametocyte carriage over time.
•Cure rates at Day 42 (PCR corrected and PCR uncorrected).
•Kaplan Maier survival analysis for all recurrences over time.
•Kaplan Maier survival analysis for new infections over time.
•Kaplan Maier survival analysis for recrudescence over time.

Secondary ID(s)

ST3073-ST3074-DM-12-002

Source(s) of Monetary Support

see section B.1