Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria

NCT ID: NCT02198807

Last Updated: 2015-06-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-12-31

Brief Summary

The objective of this study is to explore the role of fosmidomycin and piperaquine as non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when administered over three days.

Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by meeting the three key parameters of having different modes of action and different biochemical targets while exhibiting independent blood schizonticidal activity. Like the artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active against existing drug-resistant parasites. Piperaquine has a long half life protecting fosmidomycin as a much shorter lived molecule against selection of resistant parasites and will provide post-treatment prophylaxis.

Conditions

Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fosmidomycin-Piperaquine

Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days

Group Type: EXPERIMENTAL

Fosmidomycin-Piperaquine

Intervention Type: DRUG

Interventions

Fosmidomycin-Piperaquine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female subjects aged 1 to 60 years inclusive
• Body weight between 5kg and 90kg inclusive
• Acute manifestations of a mono-infection with Plasmodium falciparum as determined by either a rapid diagnostic test for adults or microscopically confirmed by an asexual parasitaemia of 1,000 to 150,000/uL and fever with an axillary temperature of > 37.5 degress C or oral/rectal/tympanic temperature of > 38.0 degrees C or history of fever during the previous 72 hours
• Compliance with contraceptive measures throughout the study period of 63 days in females of child bearing potential

Exclusion Criteria

To be eligible for inclusion in the study, subjects must NOT meet any of the following criteria:

• Signs of severe/complicated malaria according to WHO criteria
• Pregnancy as excluded by negative serum human chorionic gonadotrophin (hCG) test
• Lactation
• Mixed Plasmodium infection
• Severe vomiting on three or more occasions in the previous 24 hours
• Severe diarrhoea on four or more occasions in the previous 24 hours
• Concomitant disease masking assessment of response including

• abnormal liver function tests with bilirubin > 40 µmol/L, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) levels > x 2 upper limit of normal
• impaired renal function with creatinine level > x 2 upper limit of normal
• haemoglobin level < 7.5g/dl
• white cell count > 12000/µL
• History of cardiovascular disease including arrhythmia with QTc interval ≥ 450msec, respiratory disease including active tuberculosis, hepatic disease including jaundice, renal failure, malignancy, neurological disorders including convulsions and psychiatric disturbances
• History of immunological disease including Hepatitis A, B and C and HIV-AIDS
• Severe malnutrition
• History of hypersensitivity or adverse reactions to fosmidomycin, piperaquine, artesunate and mefloquine
• Treatment with antimalarial and antibacterial agents within the previous 28 days

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre de Recherche Médicale de Lambaréné

OTHER

Sponsor Role: collaborator

Jomaa Pharma GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Mombo-Ngoma G, Remppis J, Sievers M, Zoleko Manego R, Endamne L, Kabwende L, Veletzky L, Nguyen TT, Groger M, Lotsch F, Mischlinger J, Flohr L, Kim J, Cattaneo C, Hutchinson D, Duparc S, Moehrle J, Velavan TP, Lell B, Ramharter M, Adegnika AA, Mordmuller B, Kremsner PG. Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon. Clin Infect Dis. 2018 Jun 1;66(12):1823-1830. doi: 10.1093/cid/cix1122.

Reference Type: DERIVED

PMID: 29293893 (View on PubMed)

Other Identifiers

JP017

Identifier Type: -

Identifier Source: org_study_id