Clinical trial NCT01464125: Fosmidomycin and Azithromycin for Acute Uncomplicated Plasmodium Falciparum Malaria (P. Malaria) in Adults
Official title: Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
Study type: INTERVENTIONAL
Overall status: UNKNOWN
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: 2011-11-03
Enrollment: 43
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 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.

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.

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.

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 ≤ 18.5 kg/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 \> 125 umol/L or 3 mg/dl), haemoglobin \< 8g/dl, white cell count \> 12000/uL
* anti-malarial treatment within previous 28 days
* symptomatic AIDS

Primary outcomes:
measure: day 28 cure rate of >95%
timeFrame: 12 months
measure: Safety and Tolerance
timeFrame: 12 months
measure: Day 7 cure rate of 100%
timeFrame: 12 months
Secondary outcomes:
measure: Blood samples at 0,1,2,3,4,6,8,12,14,18,24, 26,30,36,38,42,48,50,54,60,62,66,72,78,84,90,96,108,120,144.168.240 hours
timeFrame: 12 months
measure: PCR corrected cure rates
timeFrame: 12 months
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Mahidol University
Study officials:
affiliation: Mahidol University
name: Srivicha Krudsood, Prof
role: PRINCIPAL_INVESTIGATOR
References: