Safety, Tolerability, Pharmacokinetics, and Pharmacodynam... | NCT02186002

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1	Experimental	A single oral dose of 10 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo.	Drug: ACT-451840 10 mg Drug: Placebo
Group 2	Experimental	A single oral dose of 50 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 50 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state.	Drug: ACT-451840 50 mg Drug: Placebo
Group 3	Experimental	A single oral dose of 200 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 200 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state.

Name	Type	Description	Arm Group Labels	Other Names
ACT-451840 10 mg	Drug	ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water	Group 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in systolic blood pressure from baseline up to end of study	Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.	4 days
Change in diastolic blood pressure from baseline up to end of study	Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.	4 days
Change in pulse rate from baseline up to end of study	Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.	4 days
Change in body weight from baseline up to end of study	Body weight will be measured using the same weighing scale for all subjects and throughout the study. The weighing scale should have a precision of at least 0.5 kg.	4 days
Change in heart rate from baseline up to end of study	Heart rate will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.

Secondary Outcomes

Measure	Description	Time Frame
Maximum plasma concentration (Cmax) of ACT-451840	Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing. Cmax will be calculated on the basis of the blood sampling time points.	4 days

Eligibility Module

Eligibility Criteria

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.