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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Jomaa Pharma GmbH.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Mahidol University
Thammasat University
Information provided by (Responsible Party):
Jomaa Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01464125
First received: October 26, 2009
Last updated: October 31, 2011
Last verified: October 2011
  Purpose

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 Intervention Phase
Malaria
Drug: Fosmidomycin
Drug: Azithromycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by Jomaa Pharma GmbH:

Primary Outcome Measures:
  • day 28 cure rate of >95% [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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.


  • Safety and Tolerance [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Day 7 cure rate of 100% [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • PCR corrected cure rates [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    to differentiate between reinfections and recrudescence


Enrollment: 43
Study Start Date: November 2008
Estimated Study Completion Date: December 2011
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   15 Years to 55 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

No publications provided

Responsible Party: Jomaa Pharma GmbH
ClinicalTrials.gov Identifier: NCT01464125     History of Changes
Other Study ID Numbers: JP011
Study First Received: October 26, 2009
Last Updated: October 31, 2011
Health Authority: Thailand: Ethical Committee

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

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Fosfomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014