Clinical trial NCT01002183: Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate
Official title: Evaluation of Fosmidomycin and Clindamycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Malaria
Keywords: Malaria
Plasmodium falciparum
acute uncomplicated
Lead sponsor: Jomaa Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: Mahidol University
name: Thammasat University
First posted: 2009-10-27
Enrollment: 40
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria.
timeFrame: 12 months
Secondary outcomes:
measure: 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.
timeFrame: 12 months
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Mahidol University
Study officials:
References: