Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate (JP015)

Jomaa Pharma

Status and phase

Withdrawn

Phase 2

Conditions

Malaria

Treatments

Drug: Fosmidomycin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01002183

JP015

Details and patient eligibility

About

The aim of this study is to evaluate the role of clindamycin and artesunate as possible combination partners 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

Full description

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.

Enrollment

40 estimated patients

Sex

All

Ages

15 to 55 years old

Volunteers

No Healthy Volunteers

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 ≤ 18.5kg/M2
pregnancy by history or by positive urine test
lactation
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 >125umol/L or 3mg/dl)
haemoglobin < 8g/dl
white cell count > 12000/uL
anti-malarial treatment within previous 28 days
symptomatic AIDS