Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate

Malaria Clinical Trial

— JP015  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01002183
• Other study ID #: JP015
• Status: Withdrawn
• Phase: Phase 2
• First received: October 26, 2009
• Last updated: September 26, 2011

Study information

• Verified date: August 2010
• Source: Jomaa Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 40
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Fosmidomycin
450 mg capsules, every 12 hrs for 3 days

Locations

Country	Name	City	State
Thailand	Mahidol University	Bangkok

Sponsors (3)

Lead Sponsor	Collaborator
Jomaa Pharma GmbH	Mahidol University, Thammasat University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria.		12 months	No
Secondary	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	No