Treatment of Malaria in Gabon With Fosmidomycin-Clindamycin

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00217451
• Other study ID #: 06/2002/FOS-CLIN/JP006
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: September 19, 2005
• Start date: June 2002
• Est. completion date: March 2003

Study information

• Verified date: September 2005
• Source: Albert Schweitzer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gabon: Ministry of Research
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 14 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Fosmidomycin-clindamycin

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 (6)

Beytía ED, Porter JW. Biochemistry of polyisoprenoid biosynthesis. Annu Rev Biochem. 1976;45:113-42. Review. — View Citation

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

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

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients cured by day 14
Primary	Incidence of adverse events after the start of treatment
Secondary	Parasite clearance time
Secondary	Fever clearance time
Secondary	PCR corrected day 28 cure rate

External Links

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