Clinical trial NCT02099071: Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-389949
Official title: Single-center, Double-blind, Randomized, Placebo-controlled, Single-ascending Dose and Food Interaction Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-389949 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: ACT-389949
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2014-03-28
Enrollment: 65
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a prospective, single-center, double-blind, randomized, placebo-controlled, ascending single oral dose and food interaction Phase 1 study. It will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending single oral doses of ACT-389949 in healthy male subjects. It will also investigate the effect of food on the pharmacokinetics, safety, and tolerability of a single dose of ACT-389949.


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.

Primary outcomes:
measure: Change from baseline up to 60 hours in supine systolic blood pressure
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in standing systolic blood pressure
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in supine diastolic blood pressure
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in standing diastolic blood pressure
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in pulse rate
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in body temperature
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in body weight
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in QTcB interval
timeFrame: 60 hours
measure: Change from baseline up to 60 hours in QTcF interval
timeFrame: 60 hours
measure: Treatment-emergent ECG abnormalities from baseline up to 60 hours
timeFrame: 60 hours
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-389949
timeFrame: 60 hours
measure: Area under the plasma concentration-time curve (AUC(0-t)) of ACT-389949
timeFrame: 60 hours
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-389949
timeFrame: 60 hours
measure: Time to maximum plasma concentration (tmax) of ACT-389949
timeFrame: 60 hours
measure: Plasma half life (t1/2) of ACT-389949
timeFrame: 60 hours
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: QPS Netherlands BV
Study officials:
affiliation: Actelion
name: Hans Cruz, PhD
role: STUDY_DIRECTOR
References: