Evaluation of Fosmidomycin and Clindamycin in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria

Zentopharm

Status and phase: Unknown; Phase 2

Conditions: Malaria

Treatments: Drug: Fosmidomycin and clindamycin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01361269

FosClinChildren

Details and patient eligibility

About

Few efficient drugs for malaria treatment are available so far. Due to increased exposure of these drugs and due to the high risk of development of drug resistant strains of Plasmodium falciparum, new drug combinations have to be actively investigated. The investigators will test the efficiency, safety and tolerance of combined fosmidomycin and clindamycin treatment in acute uncomplicated malaria in children aged 3-10 years.

Full description

Few efficient drugs for malaria treatment are available so far. Due to increased exposure of these drugs and due to the high risk of development of drug resistant strains of Plasmodium falciparum, new drug combinations have to be actively investigated. The goal of this study is to assess a new drug combination, fosmidomycin-clindamycin. The primary objective of the study is to assess and compare the efficacy, safety and tolerance (between sites) of fosmidomycin and clindamycin when co-administered orally over three days in the treatment of acute uncomplicated Plasmodium falciparum malaria in children in Mozambique and Gabon.

The secondary objective is to differentiate between recrudescent parasitaemia and reinfection in the event of recurrent parasitaemia developing within the 28-day follow-up period, to determine the population pharmacokinetics of fosmidomycin when co-administered orally with clindamycin and to compare the in vitro sensitivity of isolates of Plasmodium falciparum to fosmidomycin.

The trial will include 100 children aged 3-10 years, divided between clinical sites of Gabon and Mozambique.

Enrollment: 100 estimated patients

Sex: All

Ages: 3 to 10 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female subjects aged three to ten years
• Body weight ≥12kg
• Acute (symptoms lasting less than 14 days) uncomplicated P falciparum malaria
• Asexual parasitaemia between 1,000/µL and 200,000/µL
• Ability to tolerate oral therapy
• Willingness of the parent or guardian to provide informed signed consent

Exclusion criteria

• Symptoms/signs of severe malaria, according to WHO criteria (see appendix I)
• Body weight <12kg
• Other concomitant plasmodial infections (P vivax, P ovale, P malariae)
• Severe malnutrition with weight for height <70% (according to WHO tables) or clinical kwashiorkor
• Gastro-intestinal disturbance with persistent vomiting (> three episodes within previous 24 hours) and/or diarrhoea (> 5 loose stools in the preceding 24 hours)
• Concomitant disease masking assessment of response including sickle cell disease and severe cardiac, hepatic or renal impairment
• Packed cell volume (PCV) on arrival <22%
• Adequate anti-malarial treatment within previous 7 days
• Inability to tolerate oral therapy
• Parent or guardian deemed to be unsupportive
• On co-trimoxazole prophylaxis
• Any known allergies to the investigational products

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Fosmidomycin and clindamycin treatment

Experimental group

Description:

All the subject will be given fosmidomycin 30mg/kg/dose + clindamycin 10mg/kg/dose twice daily for three days (total daily dose fosmidomycin 60mg/kg, clindamycin 20mg/kg).

Treatment:

Drug: Fosmidomycin and clindamycin