Efficacy of Fosmidomycin-Clindamycin for Treating Malaria in Gabonese Children - Full Text View

Sponsor:	Albert Schweitzer Hospital
Information provided by:	Albert Schweitzer Hospital
ClinicalTrials.gov Identifier:	NCT00214643

Purpose

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.

Condition	Intervention	Phase
Malaria	Drug: Fosmidomycin Drug: clindamycin	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Comparative Assessment of the Efficacy of Fosmidomycin-Clindamycin Versus Sulfadoxine-Pyrimethamine for the Treatment of Children With Uncomplicated Plasmodium Falciparum Malaria

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Malaria

Drug Information available for: Pyrimethamine Clindamycin Clindamycin hydrochloride Clindamycin phosphate Clindamycin Palmitate Hydrochloride Clindamycin palmitate Fosmidomycin Sulfadoxine

U.S. FDA Resources

Further study details as provided by Albert Schweitzer Hospital:

Primary Outcome Measures:

Clinical and parasitological cure rate by day 28

Secondary Outcome Measures:

Safety and tolerability of the two treatments during the entire study period
Parasite clearance time
Fever clearance time

Estimated Enrollment:	160
Study Start Date:	June 2005
Estimated Study Completion Date:	July 2006

Intervention Details:

30 mg/kg

10 mg/kg

Detailed Description:

Fosmidomycin-clindamycin (30 mg/kg and 10 mg/kg) given twice daily for three days is an effective and safe combination of antibiotics which demonstrated good activity against malaria parasite in previous phase II studies in African children. In this phase III trial, the efficacy and safety of the combination will be evaluated in African children with uncomplicated P. falciparum malaria. A single dose of sulfadoxine-pyrimethamine, the standard antimalarial in Gabon, is used as comparator.

Eligibility

Ages Eligible for Study:	3 Years to 14 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00214643

Locations

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

Sponsors and Collaborators

Albert Schweitzer Hospital

Investigators

Principal Investigator:

Saadou Issifou, MD

Albert Schweitzer Hospital

More Information

Additional Information:

General information on malaria at the website of the Malaria International Foundation This link exits the ClinicalTrials.gov site

Homepage of the Medical Research Unit, Lambaréné This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

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

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

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.

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.

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.

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.

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

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. Epub 2004 Feb 16.

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. Epub 2004 Sep 21.

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.

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.

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

Study ID Numbers:	06/2005/FOS-CLIN/SP
Study First Received:	September 11, 2005
Last Updated:	February 3, 2009
ClinicalTrials.gov Identifier:	NCT00214643 History of Changes
Health Authority:	Gabon: Ministry of Research

Keywords provided by Albert Schweitzer Hospital:

Malaria
Fosmidomycin
Clindamycin
Chemotherapy
Gabon

Additional relevant MeSH terms:

Anti-Infective Agents
Protozoan Infections
Antiprotozoal Agents
Clindamycin
Sulfadoxine-pyrimethamine
Clindamycin-2-phosphate
Molecular Mechanisms of Pharmacological Action
Coccidiosis
Malaria
Enzyme Inhibitors

Pharmacologic Actions
Malaria, Falciparum
Antimalarials
Anti-Bacterial Agents
Protein Synthesis Inhibitors
Antiparasitic Agents
Fosfomycin
Therapeutic Uses
Parasitic Diseases

ClinicalTrials.gov processed this record on February 08, 2010