Study to Investigate the Tolerability, Safety, Pharmacoki... | NCT02099071

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1	Experimental	Six subjects will receive a single oral dose of ACT-389949 1 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.	Drug: ACT-389949 1 mg Drug: Placebo
Group 2	Experimental	Six subjects will receive a single oral dose of ACT-389949 5 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.	Drug: ACT-389949 5 mg Drug: Placebo
Group 3	Experimental	Six subjects will receive a single oral dose of ACT-389949 20 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.	Drug: ACT-389949 20 mg Drug: Placebo
Group 4	Experimental	Subjects will participate in two different treatment periods separated by a washout of 7-10 days between the study drug administrations. In the first treatment period six subjects will receive a single oral dose of ACT-389949 50 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach. In the second treatment period, subjects randomized to ACT-389949 will receive a single oral dose of ACT-389949 50 mg in fed condition, 30 minutes after the start of a high fat and high calorie breakfast.

Name	Type	Description	Arm Group Labels	Other Names
ACT-389949 1 mg	Drug		Group 1
ACT-389949 5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change from baseline up to 60 hours in supine systolic blood pressure	Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)	60 hours
Change from baseline up to 60 hours in standing systolic blood pressure	Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)	60 hours
Change from baseline up to 60 hours in supine diastolic blood pressure	Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)	60 hours
Change from baseline up to 60 hours in standing diastolic blood pressure	Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)	60 hours
Change from baseline up to 60 hours in pulse rate	Pulse rate will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)	60 hours
Change from baseline up to 60 hours in body temperature	Body temperature will be measured in the sitting position using the same thermometer(s) for all the subjects and throughout the study.	60 hours

Secondary Outcomes

Measure	Description	Time Frame
Maximum plasma concentration (Cmax) of ACT-389949	Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. Cmax will be calculated on the basis of the blood sampling time points.	60 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent prior to any study-mandated procedure.
Healthy Caucasian male subjects aged between 18 and 45 years (inclusive) at screening.
Subjects must agree to use reliable methods of contraception.
No clinically significant findings on physical examination at screening.
Body mass index (BMI) between 18.0 and 30.0 kg/m^2 (inclusive) at screening.
Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate (PR) 45-90 bpm (inclusive) measured at screening.
12-lead ECG without clinically relevant abnormalities, measured at screening.
Body temperature (T°) 35.5-37.5°C at screening and prior to (first) dosing.
Total and differential white blood cell (WBC) count strictly within the normal ranges at screening and on Day -1.
C-reactive protein (CRP) levels below 5 mg/L.
Hematology and clinical chemistry results (other than total and differential WBC count and CRP) not deviating from the normal range to a clinically relevant extent at screening.
Coagulation and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
Non smokers, defined as never smoked or achieved cessation for ≥ 6 months at screening.
Negative results from urine drug screen at screening.
Subjects allowing the conduct of genetic analyses on whole blood consisting of measuring the levels of messenger ribonucleic acid (mRNA) expression of mechanistic biomarkers of N-formyl-peptide receptor 2 (FPR2) and proteins involved in inflammation.
Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria:

Known allergic reactions or hypersensitivity to any excipient of the drug formulation.
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 recurrent fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
Veins unsuitable for intravenous (i.v.) puncture on either arm.
Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening.
History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
Excessive caffeine consumption.
Treatment with any prescribed or over-the-counter (OTC) medications within 2 weeks prior to (first) study drug administration or five half-lives of the medication, whichever is longer.
Any history of immunosuppressive treatment.
Chronic diseases including those with recurring periods of flare-ups and remission.
History of atopic allergy (including asthma, urticaria, eczematous dermatitis).
Signs of infection (viral, systemic fungal, bacterial or protozoal) within 4 weeks prior to (first) study drug administration.
History of acute or chronic obstructive lung disease (treated or not treated).
History of subarachnoid hemorrhage or hemolytic uremic syndrome.
Interval from the beginning of the P wave to the beginning of the QRS complex (PQ/PR interval) < 120 ms at screening.
Loss of 250 mL or more of blood, or an equivalent amount of plasma, within 3 months prior to screening.
Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
Positive results from the 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.