Active clinical trials for "Malaria"

This is a randomised two arm study, comparing artemether-lumefantrine 3 days and 5 days treatment. Patients will be randomised in blocks of ten to one of the two treatment arms. The standard regimen is twice daily for three days with a delay of at least eight hours between the first and second doses. A single of primaquine will be given to all patients on the first day of treatment for gametocytocidal activity. The initial treatment will be given under supervision, all other subsequent doses will be given to the patient to the taken at home. Patients will be followed up for nine visits over forty two days.

The study aims to provide evidence of retinal safety to support the use of tafenoquine as a potential single dose radical cure treatment for patients with Plasmodium vivax (P. vivax) malaria (i.e., co-administration of a schizonticidal drug with TQ). The study will be conducted as a single masked, randomized, placebo-controlled, parallel group design. It will assess retinal changes from baseline using spectral domain optical coherence tomography (OCT) and fundus auto fluorescence (FAF) at Month 3 (90 days) post-dose in adult healthy volunteers (participants). A placebo control group will be used to compare the results in the TQ group. Interim analysis will be conducted after completing 100 out of 300 participants in TQ group and 50 out of 150 participants in matched placebo.

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.

This will be a Proof-of-concept / Phase IIa, open label study to examine the efficacy of DSM265 in uncomplicated Plasmodium vivax and Plasmodium falciparum blood-stage malaria in adult patients. A minimum of two cohorts (20 patients) and a maximum of 6 cohorts (60 patients, 3 dose levels) will be tested. The starting dose of DSM265 for the first P. vivax and P. falciparum cohorts will be 400 mg. This dose is expected to show complete clearance of parasites by microscopy by Day 7 and a decrease in recrudescence rate assessed at Day 14 (success criteria for dose de-escalation and continuation of the study).

This will be a single-centre, 5-cohort, randomized open-label, parallel-group study in healthy volunteer subjects. This study aims to provide sufficient pharmacokinetic (PK) evidence to support the safe usage of Tafenoquine (TQ) in studies and markets where the Artemisinin-based Combination Therapies (ACTs) are the standard of care for patients with Plasmodium vivax malaria (i.e., co administration with TQ). The objective of this study is to assess the pharmacokinetics, safety and tolerability of TQ when co-administered with the chosen ACTs (AL and DHA + PQP), administered concomitantly in healthy subjects. Specifically, the study will evaluate whether there are drug-drug interactions between TQ and each of the ACTs and if these interactions are considered to be clinically significant. The co-primary objectives of this study are to characterize both the effects of a 300 milligram (mg) single dose of TQ on the pharmacokinetics; changes in (area under the concentration-time curve from 0 to time t) AUC (0-t), AUC (0-infinity), and maximum observed concentration (Cmax) of each of the two Artemisinin-based Combination Therapies (ACT) according to their prescribed dose when co-administered as well as the effects of the ACTs on the PK of TQ. A total of 120 subjects (24 subjects in each of 5 cohorts) are planned to be enrolled in order to ensure a target sample size of at least 22 subjects completing the study per cohort. All subjects will arrive in the unit at least 24 hours prior to dosing and be discharged after 72-hour post first dose assessments have been completed. Subjects will return for outpatient visits on Days 7, 14, 21, 28, and 56 after first dose.

Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. Co-administration of piperaquine plus OZ439 as Powder in Bottle (PIB) with milk results in an increase in OZ439 exposure (current estimate ~ 70% due to a small drug drug interaction). This study investigates the exposure of piperaquine and OZ439 when co-administered as piperaquine phosphate tablets and OZ439 + TPGS prototype (a formulation close to that of Phase IIb, but not identical), in order to select the appropriate doses for Phase IIb. The reference treatment is piperaquine phosphate tablets + OZ439 Powder in Bottle + full fat milk

Malaria in pregnancy is a major cause of maternal and newborn morbidity and mortality in sub-Saharan Africa]. Effective antimalarial preventive and treatment regimens can significantly reduce malaria-related morbidity and mortality in the mother and baby. However, therapeutic choices are limited by concerns about possible toxicity to the fetus and because of these concerns pregnant women are normally excluded from clinical trials. This, combined with the lack of adverse events reporting system, results in a scarcity of data on drug safety and efficacy in pregnancy. Moreover, changes in the maternal physiology in pregnancy often alter the pharmacokinetic of drugs. Artemether-lumefantrine (ALN) is a highly efficacious artemisinin-based combination therapy approved by the World Health Organisation for use in the 2nd and 3rd trimesters, although it is still infrequently used in pregnancy and there is uncertainty as to the optimum dose. The pharmacokinetics of ALN are altered in pregnancy, resulting in reduced plasma concentrations and while the standard adult dose is still effective in high transmission settings, where pregnant women have higher levels of immunity, efficacy is reduced significantly in low transmission settings where women have lower levels of immunity. Inadequate antimalarial treatment dosing in pregnancy risks treatment failure or breakthrough infection and exposure of malaria parasites to sub-therapeutic drug concentrations thus selecting for drug resistance.

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 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.