Effect of ACT-451840 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Subjects

Inclusion Criteria: * Body weight, minimum 50 kg, body mass index 18-32 kg/m\^2. * Certified healthy by detailed medical history and physical examination. * Normal vital signs. * Normal standard 12-lead electrocardiograph (ECG). * Laboratory parameters within normal range, unless the investigator considered an abnormality to be clinically irrelevant. * Use a double barrier method of contraception (male condom plus diaphragm or plus intrauterine device or plus hormonal contraceptive by female partner) for at least 14 days prior to the first dose of study drug until 90 days after the last dose. * Written informed consent prior to undertaking any study procedure. Exclusion Criteria: * Any history of malaria. * Traveled to or lived (\>2 weeks) in a malaria-endemic country in the past 12 months or planned travel to a malaria-endemic country during the course of the study. * Evidence of increased cardiovascular disease risk. * History of splenectomy. * Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician or history of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. * Presence of current or suspected serious chronic disease. * Receiving psychiatric drugs or hospitalized within the past 5 years prior to enrollment for psychiatric illness, history of suicide attempt or confinement for danger to self or others. * Frequent headaches and/or migraine, recurrent nausea, and/or vomiting. * Known inherited genetic anomaly. * Presence of acute infectious disease or fever within the 5 days prior to study product administration. * Evidence of acute illness within 4 weeks prior to screening. * Significant intercurrent disease. * Clinically significant disease or condition that might affect drug absorption, distribution or excretion. * Any investigational product study within the 12 weeks preceding the study. * Participation in a research study involving blood sampling greater than 450 mL/ unit of blood, or blood donation to a blood bank during the 8 weeks preceding the reference drug dose in the study. * Subject unwilling to defer blood donations for 6 months. * Blood donation within 1 month before inclusion. * Medical requirement for intravenous immunoglobulin or blood transfusions. * Previous blood transfusion. * Symptomatic postural hypotension. * History or presence of alcohol consumption of more than 40 g per day or drug habituation, or any prior intravenous usage of an illicit substance. * Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during the study. * Ingestion of poppy seeds within 24 hours of the screening blood test. * Excessive consumption of beverages containing xanthine bases. * Any medication within 14 days before inclusion or within 5 times the elimination half-life of the medication, vaccination within the last 28 days. * Corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants. * Recent or current therapy with an antibiotic or drug with potential antimalarial activity. * Subject who, in the judgment of the investigator, was likely to be non-compliant, or unable to cooperate because of a language problem or poor mental development; was in the exclusion period of a previous study; lived alone; who could not be contacted in case of emergency; who was directly involved in conducting the study; who had no good peripheral venous access. * Positive result on any of the following tests: hepatitis B surface antigen, anti-hepatitis B core antibodies, anti-hepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2 antibodies. * Amphetamine, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, phencyclidine, tetrahydrocannabinols, tricyclic antidepressants detected in the urine drug screen unless there was an explanation acceptable to the medical investigator. * Positive alcohol test. * Pre-existing prolongation of the interval from beginning of the Q wave until end of the T wave corrected according to Bazett's formula (QTcB interval ) and considered clinically significant. * Family history of sudden death, congenital prolongation of QTc interval, known congenital prolongation of QTc interval, or any clinical condition known to prolong the QTc interval. History of symptomatic cardiac arrhythmias or clinically relevant bradycardia. Electrolyte disturbances. * ECG abnormalities at screening which in the opinion of the investigator is clinically relevant or will interfere with the ECG analysis. * History of clinically significant ECG abnormalities. * Known hypersensitivity to ACT-451840 or any of its excipients or artemether or other artemisinin derivatives, lumefantrine or other aryl aminoalcohols. * Unwillingness to abstain from consumption of citrus fruits or their juices, as well as all fruit juices from admission to the end of the confinement period. * Any history or presence of lactose intolerance. * Ingestion of any drug since the recruitment interview (other than the doses administered in this study) which, in the opinion of the investigator, could compromise the study. * Ingestion of any drug in the week prior to dosing or during the blood sampling period which, in the opinion of the investigator, could compromise the study. * Failure to conform to the requirements of the protocol. * Detection of any drug listed in the protocol in the urine drug screen unless there was an explanation acceptable to the investigator. * Vital signs outside the reference range and clinically significant.