Active clinical trials for "Malaria"

The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village children.

The purpose of this study is to determine the efficacy of pyronaridine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children.

This is a single-centre, open-label, dose finding study using induced blood stage malaria (IBSM) infection to characterize the pharmacodynamic interaction between OZ439 and DSM265, administered around 120 minutes apart for treatment of early Plasmodium falciparum blood stage infection. The study will be conducted in up to three cohorts (n=8 per cohort) using different doses of OZ439 and DSM265. The doses of OZ439 and DSM265 that will be investigated in the first cohort will be 200 mg of OZ439 and 100mg of DSM265, both administered as single doses around 120 minutes apart. Subsequent doses in subsequent cohort(s) will be determined following a review of observed OZ439 and DSM265 safety, and pharmacokinetic and pharmacodynamic interaction outcomes, particularly the antimalarial activity of the drugs given in combination as defined by parasite clearance kinetics. The doses used in Cohort 2 and 3 may be adjusted but will not exceed the maximum acceptable doses predefined for this study (which are 400 mg for DSM265 and 500mg for OZ439) as determined in previous safety and pilot efficacy studies. The dose will be determined by the funding sponsor and the principal investigator (PI) following Safety Review team (SRT) and scientific evaluation. If no safe alternative dose can be determined the option exists to curtail the study to less than three cohorts. Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. On an outpatient basis, participants will be monitored daily via phone call and then daily (AM) from day 4 (until PCR positive for presence of malaria parasites). Once PCR positive they will be monitored twice-daily morning (AM) and evening (PM) until treatment, for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, as determined by qPCR results, participants will be admitted to the study unit and monitored. The threshold for commencement of treatment will be when PCR quantification of all participants is = 1,000 parasites/mL. If the PCR quantification of any participant is = 5,000 parasites/mL and is accompanied by a clinical symptom score >5, or if clinical or parasitological evidence of malaria occurs in any participant before all participants have reached the treatment threshold (PCR quantification of = 1,000), then treatment of that participant will begin within a 24 h period. Following treatment with OZ439 and DSM265, participants will be followed up as inpatients for at least 48 hours to ensure tolerance of the treatment and clinical response, then if clinically well on an outpatient basis for safety and clearance of malaria parasites via PCR. Compulsory commencement of treatment with Riamet® (artemether-lumefantrine) will occur on study day 16 ±3 days post OZ439 and DSM265 treatment unless required earlier. Early standard anti-malarial drug intervention can occur if either poor responses or fast responses are seen following OZ439 and DSM265 treatment. This is to ensure participant safety and to avoid participant inconvenience if useful data cannot be obtained. A poor response is defined as a decrease in parasitaemia of less than 20% from baseline by 3 days post OZ439 and DSM265 treatment. A fast response occurs when, within the seven day period following the treatment, two consecutive PCR assessments in 48 hours are negative. However, pre-emptive treatment with Riamet® can commence whenever deemed necessary by the investigator. Participants will be monitored, either in clinic, or by telephone for three days to ensure adherence to Riamet® therapy. Participants will be treated with a single dose (45 mg) of primaquine as described in section 4.3 in this protocol at the end of their Riamet® treatment if gametocytes are identified, to ensure complete clearance of any gametocytes present. Adverse events will be monitored via telephone monitoring, within the clinical research unit, and on outpatient review after malaria challenge inoculation and antimalarial study drugs administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at screening and/ or baseline and at nominated times after malaria challenge.

The weight of malaria falls most heavily on young children and pregnant women but studies of the safety of antimalarials in pregnancy and lactation are few. The only recommended medication used for radical treatment of P.vivax is primaquine. The 2010 WHO malaria guidelines recommend its use in all patients with P.vivax infection in areas of low transmission, in the absence of contraindications. Primaquine is contraindicated in pregnancy. The postpartum period presents a key opportunity to definitively treat women who suffer multiple malaria relapses during pregnancy. The 2010 WHO malaria treatment guidelines allow for primaquine use during lactation but there are no studies to date quantifying primaquine excretion in breast milk and the dose that breastfed infants would be exposed to is unknown. The investigators propose to study the pharmacokinetics of primaquine in maternal and infant plasma and in breast milk during a 14 day radical treatment of P.vivax. Some inferences about the expected behavior of primaquine in lactation can be drawn from its known pharmacologic properties. Primaquine pharmacokinetics have been well characterized in healthy subjects and malaria patients after single and multiple oral dosing. Peak concentrations are reached within 2-3 hours after dosing and the plasma elimination half-life is ~7 hours. It is extensively distributed in the tissue and largely metabolized to inert carboxyprimaquine, the major plasma metabolite, which undergoes further biotransformation to unknown metabolites that are probably more toxic than the parent compound. The identification of other metabolites in humans has been difficult to pursue because the expected aminophenol metabolites are unstable. No pharmacokinetic studies have been done to measure primaquine excretion in breast milk. A few studies have been done of other antimalarials during lactation and have shown low levels of drug in breast milk during treatment.

The purpose of this two part study is to test the safety and efficacy of Tafenoquine (with Cholorquine) as a radical cure for Plasmodium vivax (P.vivax) malaria relative to the control Chloroquine.Part 1 aims to select an efficacious and well tolerated dose that can be co-administered with Chloroquine. Part 2 will investigate the safety and efficacy of the selected dose (300 mg tafenoquine) in the treatment and radical cure of Plasmodium Vivax Malaria.

The combination of pyronaridine and artesunate is an antimalarial therapy in development. This mass balance study is intended to determine the rate and extent of excretion of total radioactivity in urine and feces following administration of a single oral micro-dose of 14C-pyronaridine in humans.

This randomized clinical trial will be conducted in subjects with uncomplicated Plasmodium vivax malaria during November 2010 to March 2012. The aim of the study is to compare the efficacy and safety of artesunate-amodiaquine plus primaquine (AS-AQ + PQ) and dihydroartemisinin-piperaquine plus primaquine (DHP + PQ) in uncomplicated vivax malaria. The significance of the study is to find alternative drug for treating patients with vivax malaria in case the standard treatment is not available or become resistance. This study will give thorough information about the efficacy and safety of 2 artemisinin-based combination therapies (ACTs) in combination with primaquine. It will also inform the Indonesian Ministry of Health on their suggested policies for radical cure of vivax malaria, and provides evidence based treatment options for chloroquine resistant vivax malaria. This study will also provide information about prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and G6PD variants in North Sumatera population.

The purpose of this study is to assess the effectiveness of different malaria control strategies in the first year of life. The effectiveness of delivering an intermittent screening and treatment programme with dihydroartemisinin-piperaquine (DHP), linked to local immunization programmes, will be compared to the current practice of passive case detection of malaria. This study has two objectives: To assess the effectiveness of intermittent screening and treatment with dihydroartemisinin-piperaquine (DHP) administered at 2, 3, 4 and 9 months of age compared with the current practice of passive detection and treatment for malaria in an area with high drug resistance levels to both P. falciparum and P. vivax. To evaluate the safety, efficacy and population pharmacokinetics of DHP in children under 1 year of age.

Pediatric cerebral malaria (CM) affects more than 3 million children each year killing ~20% and leaving one third of survivors with long term neurologic and psychiatric sequelae. Seizures occur commonly with CM and are associated with an increased risk of death and neuropsychiatric disabilities. In this Malawi-based, safety and feasibility study of enteral levetiracetam in pediatric CM, the investigators will lay the groundwork for future efficacy studies aimed at improving seizure control and ultimately decreasing the neurologic morbidity of pediatric CM.

There is a need for paediatric formulations that permit accurate dosing and enhance patient compliance. However, for the treatment of malaria, scarce paediatric-friendly formulations are available on the market. Thus, a new water dispersible formulation of eurartesim has been developed for oral administration. Aim of this study is to provide data on pharmacokinetic profile, safety and efficacy of this new paediatric formulation and compare it with the crushed film coated tablet in infant patients (6 to ≤12 months of age) suffering from uncomplicated Plasmodium falciparum malaria. Furthermore, a Pharmacokinetic/Pharmacodynamic(PK/PD) modelling will be built up to establish PK/PD relationship in adult and paediatric populations.