Efficacy of Fosmidomycin-Clindamycin for Treating Malaria in Gabonese Children

NCT00214643 | Completed Phase 3

• 1 other identifier: 06/2005/FOS-CLIN/SP
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

There is a necessity for the development of new malaria drugs. 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. Previous small studies have shown that in combination with clindamycin, an commonly used antibiotic, it is highly effective and safe when given for three days, leading to a total cure in most patients. The current study will evaluate its efficacy in a larger population in Gabon, and compare its effect with the generally used drug, sulfadoxine-pyrimethamine.

Conditions

Malaria

Keywords

Malaria; Fosmidomycin; Clindamycin; Chemotherapy; Gabon

Outcome Measures

Primary Outcomes (1)

• Clinical and parasitological cure rate by day 28

Secondary Outcomes (3)

• Safety and tolerability of the two treatments during the entire study period

• Parasite clearance time

• Fever clearance time

Interventions

Fosmidomycin DRUG

30 mg/kg

clindamycin DRUG

10 mg/kg

Eligibility Criteria

• Age: 3 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Uncomplicated P. falciparum malaria
• P. falciparum asexual parasitaemia between 1,000/µL and 100,000/µL
• Body weight between 10 - 65 kg
• Ability to tolerate oral therapy
• Informed consent, oral assent of the child, if possible
• Residence in study area

You may not qualify if:

• Adequate anti-malarial treatment within the previous 7 days
• Antibiotic treatment for the current infection
• Previous participation in this clinical trial
• Haemoglobin \< 7 g/dl
• Haematocrit \< 23 %
• Leucocyte count \> 15,000 /µL
• Mixed plasmodial infection
• Severe malaria (as defined by WHO)
• Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection)
• Concomitant disease masking assessment of response
• History of allergy or intolerance against trial medication

Sponsors & Collaborators

• Albert Schweitzer Hospital, Netherlands: lead
• Albert Schweitzer Hospital: collaborator

Study Sites (1)

Medical Research Unit, Lambaréné

Lambaréné, Moyen-Ogooué Province, B.P. 118, Gabon

Location

Related Publications (15)

• Kuemmerle HP, Murakawa T, Sakamoto H, Sato N, Konishi T, De Santis F. Fosmidomycin, a new phosphonic acid antibiotic. Part II: 1. Human pharmacokinetics. 2. Preliminary early phase IIa clinical studies. Int J Clin Pharmacol Ther Toxicol. 1985 Oct;23(10):521-8.

  PMID: 4066076 BACKGROUND

• Kuemmerle HP, Murakawa T, Soneoka K, Konishi T. Fosmidomycin: a new phosphonic acid antibiotic. Part I: Phase I tolerance studies. Int J Clin Pharmacol Ther Toxicol. 1985 Oct;23(10):515-20.

  PMID: 4066075 BACKGROUND

• 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)(Pt 2):517-24. doi: 10.1042/bj2950517.

  PMID: 8240251 BACKGROUND

• Kuzuyama T, Shizimu T, Takashi S and Seto H. Fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway of isoprenoid biosynthesis. Tetrahaedron Lett 1998;39:7913-6

  BACKGROUND

• Zeidler J, Schwender J, Müller C, et al. Inhibition of the non-mevalonate 1-deoxy-D-xylulose-5-phosphate pathway of plant isoprenoid biosynthesis by fosmidomycin. Z Naturforsch 1998;53:980-6

  BACKGROUND

• 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. doi: 10.1073/pnas.95.5.2105.

  PMID: 9482846 BACKGROUND

• Takahashi S, Kuzuyama T, Watanabe H, Seto H. A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9879-84. doi: 10.1073/pnas.95.17.9879.

  PMID: 9707569 BACKGROUND

• 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. doi: 10.1126/science.285.5433.1573.

  PMID: 10477522 BACKGROUND

• Kohler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS. A plastid of probable green algal origin in Apicomplexan parasites. Science. 1997 Mar 7;275(5305):1485-9. doi: 10.1126/science.275.5305.1485.

  PMID: 9045615 BACKGROUND

• Fichera ME, Roos DS. A plastid organelle as a drug target in apicomplexan parasites. Nature. 1997 Nov 27;390(6658):407-9. doi: 10.1038/37132.

  PMID: 9389481 BACKGROUND

• Borrmann S, Adegnika AA, Matsiegui PB, Issifou S, Schindler A, Mawili-Mboumba DP, Baranek T, Wiesner J, Jomaa H, Kremsner PG. Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children. J Infect Dis. 2004 Mar 1;189(5):901-8. doi: 10.1086/381785. Epub 2004 Feb 16.

  PMID: 14976608 BACKGROUND

• Borrmann S, Issifou S, Esser G, Adegnika AA, Ramharter M, Matsiegui PB, Oyakhirome S, Mawili-Mboumba DP, Missinou MA, Kun JF, Jomaa H, Kremsner PG. Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria. J Infect Dis. 2004 Nov 1;190(9):1534-40. doi: 10.1086/424603. Epub 2004 Sep 21.

  PMID: 15478056 BACKGROUND

• Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, Marsh K. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet. 1999 Feb 20;353(9153):632-6. doi: 10.1016/s0140-6736(98)07318-8.

  PMID: 10030329 BACKGROUND

• Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.

  PMID: 11377597 BACKGROUND

• Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000 Apr;94 Suppl 1:S1-90. No abstract available.

  PMID: 11103309 BACKGROUND

Related Links

• General information on malaria at the website of the Malaria International Foundation
• Homepage of the Medical Research Unit, Lambaréné

MeSH Terms

Conditions

Malaria

Interventions

fosmidomycin; Clindamycin

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Saadou Issifou, MD

  Albert Schweitzer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: UNKNOWN

Study Record Dates

• First Submitted: September 11, 2005
• First Posted: September 22, 2005
• Study Start: June 1, 2005
• Study Completion: July 1, 2006
• Last Updated: February 4, 2009

Record last verified: 2009-02

Locations

GA (1)