Fosmidomycin and Azithromycin for Acute Uncomplicated Plasmodium Falciparum Malaria (P. Malaria) in Adults
Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
  • Phase

    Phase 2
  • Study Type

  • Status

    Unknown status
  • Study Participants

The aim of this study is to evaluate the role of azithromycin as a possible combination partner for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile.
The scientific rationale for the use of this combination is to inhibit the ability of the parasite to synthesise isoprenoids, as precursors of many essential compounds including sterols, carotenoids and ubiquinones. This is effected through blockade of the non-mevalonate pathway by fosmidomycin as a potent inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase coupled with targeting of protein biosynthesis by azithromycin through binding to the 50S ribosomal subunit. This mode of action contrasts with the ability of the human host to utilise the mevalonate pathway for isoprenoid synthesis and accounts for the safety profiles of both drugs through the mechanism of selective toxicity. Moreover it affords protection against cross resistance with existing chemotherapeutic agents.

The dose of fosmidomycin, equivalent to 30mg/kg twice daily for three days, selected for evaluation in this proof of concept study is derived from the highest dose that was administered in the Phase I safety tolerance studies. While the recommended dose of azithromycin for the treatment of bacterial infections is 250mg daily for three days, higher doses of up to 1500mg daily for three days have been evaluated for the treatment of malaria, in combination with artesunate or quinine.
Study Started
Nov 30
Primary Completion
Oct 31
Study Completion
Dec 31
Last Update
Nov 03

Drug Fosmidomycin

Fosmidomycin sodium capsules 450 mg x 4 twelve-hourly for three days

Drug Azithromycin

Azithromycin capsules 250 mg x 3 twelve-hourly for three days

Fos-Azi Experimental

Open label single arm concurrent administration of fosmidomycin and azithromycin.


Inclusion Criteria:

male and female subjects aged 15 to 55 years
body mass index ≥ 18.5kg/M2
uncomplicated P falciparum malaria with acute manifestations
asexual parasitaemia between 500uL and 100,000uL
ability to tolerate oral therapy
able to give informed signed consent

Exclusion Criteria:

signs of severe malaria, according to WHO criteria
body mass index ≤ 18.5 kg/M2
pregnancy by history or by positive urine test
mixed plasmodial infection
concomitant disease masking assessment of response, including diabetes, uncontrolled hypertension, heart failure, hepatic dysfunction (alanine-amino transferase > 150 U/L), renal impairment (creatinine > 125 umol/L or 3 mg/dl), haemoglobin < 8g/dl, white cell count > 12000/uL
anti-malarial treatment within previous 28 days
symptomatic AIDS
No Results Posted