Clinical trial NCT02223832: Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects
Official title: Single-center, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of a Single Dose of 40 mg ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ACT-128800
Safety
Tolerability
Pharmacokinetics
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2014-08-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: This is a study to evaluate the relative pharmacokinetic properties and the tolerability and safety of ACT-128800 in Japanese and Caucasian healthy male and female subjects after single-dose administration.

Detailed description: 10 Japanese and 10 Caucasian healthy male and female subjects in a one to one male to female ratio will be included in the study. Japanese and Caucasian subjects will be matched for body weight.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to any study-mandated procedure.
* Japanese or Caucasian. (Japanese subjects: both parents of the subject are Japanese \[born in Japan\]. Caucasian subjects: both parents of the subject are Caucasian).
* Body mass index between 18 and 28 kg/m\^2, inclusive.
* Women not of childbearing potential:
* Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to drug intake on Day 1; use a reliable method of contraception and continue this contraception for the duration of the study and for at least 2 months after study drug intake. In addition, her partner must use a condom.
* Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate (HR) 50-95 beats per minute (inclusive).
* 12-lead electrocardiogram without clinically relevant abnormalities at screening.
* Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
* Negative results from urine drug screen at screening.
* Ability to communicate well with the Investigator (if necessary with the help of an interpreter) and to understand and comply with the requirements of the study.

Exclusion Criteria:

* Electrocardiograph PQ/PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) \> 200 milliseconds at screening.
* Nursing woman.
* History of asthma or chronic obstructive pulmonary disease.
* Known hypersensitivity to any excipients of the drug formulation.
* Treatment with another investigational drug within 3 months prior to screening.
* Excessive caffeine consumption, defined as \> 800 mg per day at screening.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
* Any cardiac condition or illness, including ECG abnormalities, with a potential to increase the cardiac risk of the subject.
* Smoking within the last month prior to screening.
* Any immunosuppressive treatment within 6 weeks before study drug administration.
* Previous treatment with any prescribed or over-the-counter medications within 2 weeks prior to screening.
* Loss of 250 mL or more of blood within 3 months prior to screening.
* Lymphopenia (\< 1,000 lymphocytes/μL).
* Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration.
* Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
* Positive results from human immunodeficiency vrus serology at screening.
* Legal incapacity or limited legal capacity at screening.
* History of alcoholism or drug abuse.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Change in systolic blood pressure from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in diastolic blood pressure from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in pulse rate from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in body temperature from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in forced expiratory volume in 1 second (FEV1) from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in forced vital capacity (FVC) from baseline up to end of study
timeFrame: Up to 10 days
measure: Number of treatment-emergent abnormalities on physical examination up to end of study
timeFrame: Up to 10 days
measure: Change in heart rate from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in QT interval (time interval from beginning of the Q wave until end of the T wave) calculated according to Bazett's correction (QTcB) from baseline up to end of study
timeFrame: Up to 10 days
measure: Change in QT interval (time interval from beginning of the Q wave until end of the T wave) calculated according to Fridericia's correction (QTcF) from baseline up to end of study
timeFrame: Up to 10 days
measure: Number of treatment-emergent electrocardiogram abnormalities up to end of study
timeFrame: Up to 10 days
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-128800
timeFrame: 144 hours
measure: Time to maximum plasma concentration (tmax) of ACT-128800
timeFrame: 144 hours
measure: Area under the plasma concentration-time curve (AUC(0-t)) of ACT-128800
timeFrame: 144 hours
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-128800
timeFrame: 144 hours
measure: Plasma half life (t1/2) of ACT-128800
timeFrame: 144 hours
measure: Change in lymphocyte count from baseline up to end of study
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Hawaii Clinical Research Center
state: Hawaii
Study officials:
affiliation: Actelion Pharmaceuticals Limited
name: Patrick Brossard, PhD
role: STUDY_DIRECTOR
References: