Efficacy of Fosmidomycin-Clindamycin for Treating Malaria in Gabonese Children

Malaria Clinical Trial

Official title:

A Comparative Assessment of the Efficacy of Fosmidomycin-Clindamycin Versus Sulfadoxine-Pyrimethamine for the Treatment of Children With Uncomplicated Plasmodium Falciparum Malaria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00214643
• Other study ID #: 06/2005/FOS-CLIN/SP
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2005
• Last updated: February 3, 2009
• Start date: June 2005
• Est. completion date: July 2006

Study information

• Verified date: February 2009
• Source: Albert Schweitzer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gabon: Ministry of Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 14 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Fosmidomycin
30 mg/kg
• clindamycin
10 mg/kg

Locations

Country	Name	City	State
Gabon	Medical Research Unit, Lambaréné	Lambaréné	Moyen Ogooué

Sponsors (1)

Lead Sponsor	Collaborator
Albert Schweitzer Hospital

Country where clinical trial is conducted

Gabon, 

References & Publications (15)

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. — View Citation

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. — View Citation

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

Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova 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. — View Citation

Köhler 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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000 Apr;94 Suppl 1:S1-90. Review. — View Citation

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. — View Citation

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. — View Citation

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

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical and parasitological cure rate by day 28
Secondary	Safety and tolerability of the two treatments during the entire study period
Secondary	Parasite clearance time
Secondary	Fever clearance time

External Links

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