Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Evaluation of Fosmidomycin and Clindamycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria

Conditions
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Malaria

Intervention / Treatment
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* Drug: Fosmidomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: single arm<br>Fos-clin/Arte | Drug: Fosmidomycin<br>* 450 mg capsules, every 12 hrs for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Plasmodium falciparum, acute uncomplicated