Active clinical trials for "Malaria"

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.

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 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 study aims to investigate the concentration dependent effects of OZ439 on the clearance of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based dosing. The adaptive investigation of a range of doses will provide the best chance of accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on parasitaemia will be investigated.

The investigators hypothesize that the addition of primaquine (PQ) to both artemether-lumefantrine (AL) and chloroquine (CQ) for the treatment of Plasmodium vivax infection will result in decreased chance of relapse by about 60%. The investigators plan to assess the therapeutic efficacy of AL compared to combined AL + PQ and CQ compared to combined CQ + PQ against P. vivax infection. They also plan to determine the number of recurrent vivax episodes in patients receiving PQ compared to those who don't receive PQ. Patients aged above 1 year with symptomatic malaria presenting to health centers will be enrolled for treatment with AL, AL+PQ, CQ, or CQ+PQ for P. vivax infection. Phase 1 of the study will monitor the clinical, parasitological, and hematological parameters for P. vivax infection over a 42-day follow-up period, which will be used to evaluate drug efficacy. Phase 2 will continue monthly follow-up of these patients for one year to assess frequency of recurring vivax infections. Results from this research study will be used to assist Ethiopia in assessing their current national malaria drug policies.

Plasmodium falciparum causes malaria and approximately 665 000 deaths each year. chloroquine and sulphadoxine-pyrimethamine resistant P. falciparum are widespread. An artemisinin derivative combined with lumefantrine, amodiaquine or piperaquine is therefore recommended for the treatment of malaria in Africa. However, artemisinin resistance appears to be developing and resistance/tolerance to amodiaquine and lumefantrine exists. We are presently conducting a study in Guinea-Bissau. Preliminary data indicates that the effectiveness and availability of artemether-lumefantrine (AL), the 1st line drug, is poor. Consequently there is a need for another treatment option. Dihydroartemisinin-piperaquine (DP) has been shown to be efficacious and well tolerated in several African countries and is therefore such an option. A clinical trial comparing the safety and efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine is therefore needed. Parents to children seeking Bandim Health Centre (CSB) with symptoms compatible with malaria will be informed of the study. If accepting and the child fulfil the inclusion criteria, the child will be randomised to treatment with either AL or DP. The treatment will be given supervised at the health centre in the morning and the evening on day 0, day 1, and day 2. At each visit and in the morning on day 3, the child will be examined, the mother asked for any symptoms and signs of side-effects, the temperature measured. Furthermore, a blood sample will be taken for examination of malaria parasites. On day 0 samples for measurement of antimalarial drugs and for genotyping of the parasites will be taken on filterpaper. In a subgroup of 50 children a blood sample for in vitro culturing and for analysis of the number of leucocytes will also be taken. After having finished the treatment the children will be followed on day 7 and then once a week until day 42. At each visit the condition of the child will be examined and a bloodsample taken for examination of parasites in the blood. Furthermore, a filterpaper bloodsample will be collected for measurement of the drug concentration of if the child has recrudescence for genotyping of the parasites. On day 0, 3 and 42 the haemoglobin level will be examined. The result of the two treatments will be evaluated by comparing the number of children with recurrent parasitaemia, both corrected and uncorrected (recrudescence vs. reinfections). This will be presented as adequate clinical and parasitological response rates PCR-corrected and PCR-uncorrected. Furthermore, the chance in haemoglobin level from day 0 till day 3 and till day 42 will be compared. The concentration of the antimalarial drug in the blood samples taken at the visit before the re-parasitaemia will be capered to the concentrations in children without re-parasitaemia. Assuming a 20% loss to follow up a total of 346 children should be included. For the children included, health care and medications at Bandim Health Centre will be free during the study period but no other gifts or payments will be made. Results will be presented to the staff at the Bandim health centre and the ministry of Health and will be published in an international peer reviewed journal.

This is a two-arm study aiming at recruiting 150 patients to assess the efficacy of Amodiaquine-Artesunate (ASAQ) and Artemether-Lumefantrine (AL) in patients with a microscopy positive diagnosis of malaria in Nanoro, Burkina Faso and assess the performance of the Rapid Diagnosis Tests (RDTs) compared to the microscopy.

The purpose of this study is to demonstrate that ArTiMist (sublingual artemether spray) is better than intravenous quinine in reducing parasite counts by >= 90% within 24 hours after the start of treatment in children with severe malaria, or uncomplicated malaria with gastrointestinal complications

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 purpose of this study is to determine the safety and impact of ivermectin, administered as single or repeated dose, in combination with artemether-lumefantrine in reducing the proportion of mosquitoes that survive and become infected after feeding on a blood meal from a malaria-infected individual.