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

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

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.

Study Overview

• Status: Unknown
• Conditions: Malaria
• Intervention / Treatment: Drug: Fosmidomycin and clindamycin

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Saadou Issifou, MD PhD; Phone Number: 0024106106256; Email: isaadou2002@yahoo.fr
• Study Contact Backup: Name: Ana Babic, PhD; Phone Number: 004970712986020; Email: anababic99@yahoo.fr

Study Locations

• Gabon
  • Lambarene, Gabon
    • Medical Research Unit, Albert Schweitzer Hospital
    • Contact: Saadou Issifou; Phone Number: 0024106106256; Email: isaadou2002@yahoo.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fosmidomycin and clindamycin treatment; 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).	Drug: Fosmidomycin and clindamycin; The study drugs will be co-administered under supervision by a study physician or nurse in doses of fosmidomycin 30mg/kg/dose + clindamycin 10mg/kg/dose twice daily for three days (total daily dose fosmidomycin 60mg/kg, clindamycin 20mg/kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate	Cure rate at day 28 will be determined by PCR	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cure rate	The secondary endpoints will be the cure rate on Day 7 and the parasite and fever clearance times.	day 7

Collaborators and Investigators

• Sponsor: Zentopharm GmbH
• Collaborators: Centro de Investigação em Saúde de Manhiça; Albert Schweitzer Hospital
• Investigators: Principal Investigator: Saadou Issifou, MD PhD, Medical Research Unit, Albert Schweitzer Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Anticipated): September 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Estimate): May 26, 2011
• Last Update Submitted That Met QC Criteria: May 25, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Fosmidomycin
• Other Study ID Numbers: FosClinChildren