Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-451840 in Healthy Subjects (Part A)

Single-center, Double-blind, Placebo-controlled, Randomized, Single-ascending Dose, With Nested Cross-over for Food Effect, to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-451840 in Healthy Subjects (Part A)

The primary objective of the study was to evaluate the safety and tolerability of ACT-451840 in healthy male subjects.Secondary objectives were : to investigate the pharmacokinetics (PK) of ACT-451840; to investigate the effect of food on the PK of ACT-451840; to evaluate the urinary excretion of ACT-451840 and to investigate the antimalarial activity of ACT-451840.

Inclusion Criteria:

• Signed informed consent in the local language prior to any study-mandated procedure.
• Body mass index (BMI) of 18.0 to 28.0 kg/m2 (inclusive) at screening.
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive), measured on the dominant arm, after 5 min in the supine position at screening.
• 12-lead electrocardiogram without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
• Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
• No clinically significant findings on the physical examination at screening.
• Negative results from urine drug screen at screening.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
• Subject covered by Health Insurance system and/or in compliance with the recommendations of the National Law in force relating to biomedical research.
• If the subject's partner could become pregnant, reliable methods of contraception must be used from the time of the first administration of study medication until 3 months following administration of the last dose of study medication.

Exclusion Criteria:

• Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s).
• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Documented history of chronic liver or gall bladder disease.
• Documented history of hemolytic anemia.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).
• Previous exposure to the study medication.
• Treatment with another investigational drug within 3 months prior to screening or participation in more than four investigational drug studies within the 12 months prior to screening.
• Subject in the exclusion period of a previous clinical study.
• Subject who had received more than 4,500 Euros as indemnities for his participation in a biomedical research within the 12 last months, including the indemnities for the present study.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption, defined as 800 mg or more per day at screening.
• Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study.
• Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St. John's Wort) within 2 weeks prior to first study drug administration.
• Loss of 250 mL or more of blood within 3 months prior to screening.
• Positive results from the hepatitis (hepatitis B and C) serology, except for vaccinated subjects.
• Positive results from human immunodeficiency virus serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.