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Fosmidomycin and Azithromycin for Acute Uncomplicated Plasmodium Falciparum Malaria (P. Malaria) in Adults (JP011)

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ClinicalTrials.gov Identifier: NCT01464125
Recruitment Status : Unknown
Verified October 2011 by Jomaa Pharma GmbH.
Recruitment status was:  Active, not recruiting
First Posted : November 3, 2011
Last Update Posted : November 3, 2011
Sponsor:
Collaborators:
Mahidol University
Thammasat University
Information provided by (Responsible Party):
Jomaa Pharma GmbH

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.

Condition or disease Intervention/treatment Phase
Malaria Drug: Fosmidomycin Drug: Azithromycin Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
Study Start Date : November 2008
Actual Primary Completion Date : October 2009
Estimated Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Fos-Azi
Open label single arm concurrent administration of fosmidomycin and azithromycin.
Drug: Fosmidomycin
Fosmidomycin sodium capsules 450 mg x 4 twelve-hourly for three days

Drug: Azithromycin
Azithromycin capsules 250 mg x 3 twelve-hourly for three days




Primary Outcome Measures :
  1. day 28 cure rate of >95% [ Time Frame: 12 months ]

    Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria.

    Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.


  2. Safety and Tolerance [ Time Frame: 12 months ]
    To determine the safety and tolerance of fosmidomycin and azothromycin when co-administered orally over three days. Safety and tolerability will be evaluated by the incidence, intensity, seriousness and relationship of new adverse event(s), and clinically relevant laboratory changes. The drug will be considered as safe if there are no serious adverse events attributable to the study drug.

  3. Day 7 cure rate of 100% [ Time Frame: 12 months ]

    Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria.

    Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.



Secondary Outcome Measures :
  1. 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 [ Time Frame: 12 months ]
    pharmacokinetic profile. Full profiles of pharmacokinetic parameters including Cmax, Tmax, peak, trough, Vd, AUC, T1/2a, T1/2t, renal and total Cl will be derived.

  2. PCR corrected cure rates [ Time Frame: 12 months ]
    to differentiate between reinfections and recrudescence



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Ages Eligible for Study:   15 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01464125


Locations
Thailand
Mahidol University
Bangkok, Thailand, 10400
Sponsors and Collaborators
Jomaa Pharma GmbH
Mahidol University
Thammasat University
Investigators
Principal Investigator: Srivicha Krudsood, Prof Mahidol University

Responsible Party: Jomaa Pharma GmbH
ClinicalTrials.gov Identifier: NCT01464125     History of Changes
Other Study ID Numbers: JP011
First Posted: November 3, 2011    Key Record Dates
Last Update Posted: November 3, 2011
Last Verified: October 2011

Keywords provided by Jomaa Pharma GmbH:
Malaria
Plasmodium falciparum
acute uncomplicated

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Fosmidomycin
Fosfomycin
Anti-Bacterial Agents
Anti-Infective Agents