JP015: Fosmidomycin With Clindamycin or With Clindamycin Plus Artesunate
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: single arm Fos-clin/Arte |
Drug: Fosmidomycin
450 mg capsules, every 12 hrs for 3 days
|
Outcome Measures
Primary Outcome Measures
- Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria. [12 months]
Secondary Outcome Measures
- 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]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mahidol University | Bangkok | Thailand | 10400 |
Sponsors and Collaborators
- Jomaa Pharma GmbH
- Mahidol University
- Thammasat University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JP015