Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate

Jomaa Pharma GmbH40 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malaria

Interventions

FosmidomycinDRUG

450 mg capsules, every 12 hrs for 3 days

Eligibility

Sex: ALLMin age: 15 YearsMax age: 55 Years

Medical Language ↔ Plain English

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

Locations (1)

Mahidol University

Bangkok, Thailand

Outcomes

Primary Outcomes

Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria.

Time frame: 12 months

Secondary Outcomes

To determine the viability and infectivity of gametocytes induced by the co-administration of fosmidomycin with clindamycin or with clindamycin plus artesunate to adult subjects with acute uncomplicated Plasmodium falciparum malaria.

Time frame: 12 months

Data from ClinicalTrials.gov

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