Treatment of Malaria in Gabon With Fosmidomycin-Clindamycin

Condition(s) targeted: Malaria

Intervention: Fosmidomycin-clindamycin (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Albert Schweitzer Hospital, Netherlands

Official(s) and/or principal investigator(s):
Steffen Borrmann, MD, Principal Investigator, Affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, kilifi, Kenya
Peter G. Kremsner, MD, FRCP, Principal Investigator, Affiliation: Medical Research Unit, Lambaréné

Some antibiotics are also effective against malaria parasites. Fosmidomycin is an antibiotic that has been shown to be effective against malaria, although it cannot achieve a total cure in all patients. A previous small study has shown that in combination with clindamycin, an commonly used antibiotic, it is highly effective and safe, in asymptomatic carriers of malaria parasites. The current study will evaluate the efficacy and safety of the combination given for three days in children with uncomplicated malaria in Gabon.

Official title: Evaluation of Fosmidomycin in Combination With Clindamycin in Children With Acute Uncomplicated Plasmodium Falciparum Malaria

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

Proportion of patients cured by day 14

Incidence of adverse events after the start of treatment

Secondary outcome:

Parasite clearance time

Fever clearance time

PCR corrected day 28 cure rate

Detailed description: The treatment of malaria is becoming increasingly difficult due to the development of Plasmodium falciparum strains resistant to commonly used antimalarials. Fosmidomycin was shown to be well tolerated and fast-acting in paediatric outpatients and adults, but late recrudescences preclude its use as monotherapy. Clindamycin was identified as a suitable combination partner following the demonstration of synergistic inhibition of plasmodial growth by in vitro and animal studies.

In this study, the safety and efficacy of fosmidomycin-clindamycin (30 mg/kg plus 10 mg/kg) twice daily for three days is assessed in children with acute uncomplicated P. falciparum malaria.

Minimum age: 12 Months. Maximum age: 14 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Uncomplicated P. falciparum malaria with acute manifestation

- Asexual parasitemia between 1,000-100,000/μL

- Body weight between 5-65 kg

- Ability to tolerate oral therapy

- Informed consent, oral agreement of the child if appropriate

- Residence in the study area for the duration of at least 4 weeks

Exclusion Criteria:

- Adequate anti-malarial treatment within the previous 7 days

- Antibiotic treatment for a concurrent infection

- Haemoglobin <7g/dL

- Hematocrit <25%

- Leukocyte count >15,000/μL

- Mixed plasmodial infection

- Severe malaria, any other severe underlying disease

- Concomitant disease masking assessment of treatment response

- Inflammatory bowel disease, and any other disease causing fever.

Medical Research Unit, Lambaréné, Lambaréné, Moyen Ogooué B.P. 118, Gabon

General information on malaria at the website of the Malaria Foundation International

Homepage of Medical Research Unit, Lambaréné

Related publications:

Beytia ED, Porter JW. Biochemistry of polyisoprenoid biosynthesis. Annu Rev Biochem. 1976;45:113-42. Review. No abstract available.

Lois LM, Campos N, Putra SR, Danielsen K, Rohmer M, Boronat A. Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2105-10.

Rohmer M, Knani M, Simonin P, Sutter B, Sahm H. Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem J. 1993 Oct 15;295 ( Pt 2):517-24.

Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Turbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999 Sep 3;285(5433):1573-6.

Clinical study report for Protocol JP 001 – Evaluation of fosmidoymcin in adult patients with acute uncomplicated Plasmodium falciparum malaria. 2001. World Health Organisation, Geneva, Switzerland and Jomaa Pharmaka GmbH, Germany

Wiesner J, Henschker D, Hutchinson DB, Beck E, Jomaa H. In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin. Antimicrob Agents Chemother. 2002 Sep;46(9):2889-94.

Starting date: June 2002
Ending date: March 2003
Last updated: September 19, 2005