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Completed

NCT Number: NCT02223832

Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects

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.

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Key information

Conditions

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Hawaii Clinical Research Center

Honolulu, Hawaii, 96813, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ACT-128800

Drug

Primary outcomes

  1. Change in systolic blood pressure from baseline up to end of study

    Time frame: Up to 10 days

    Blood pressure shall be measured using an automatic oscillometric device, always on the leading (writing) arm. Measurements shall be taken in the supine position after having rested for at least a 5 min period.

  2. Change in diastolic blood pressure from baseline up to end of study

    Time frame: Up to 10 days

    Blood pressure shall be measured using an automatic oscillometric device, always on the leading (writing) arm. Measurements shall be taken in the supine position after having rested for at least a 5 min period.

  3. Change in pulse rate from baseline up to end of study

    Time frame: Up to 10 days

    Pulse rate shall be measured using an automatic oscillometric device, always on the leading (writing) arm. Measurements shall be taken in the supine position after having rested for at least a 5 min period.

  4. Change in body temperature from baseline up to end of study

    Time frame: Up to 10 days

    Body temperature shall be measured in a supine position using the same thermometer throughout the study.

  5. Change in forced expiratory volume in 1 second (FEV1) from baseline up to end of study

    Time frame: Up to 10 days

    FEV1 assessments shall be performed in a standardized manner as per the American Thoracic Society standards. Three good test breaths will be measured; the highest FEV1 value from these three breath tests will be recorded.

  6. Change in forced vital capacity (FVC) from baseline up to end of study

    Time frame: Up to 10 days

    FVC assessments shall be performed in a standardized manner as per the American Thoracic Society standards. Three good test breaths will be measured; the highest FVC value from these three breath tests will be recorded.

  7. Number of treatment-emergent abnormalities on physical examination up to end of study

    Time frame: Up to 10 days

    Physical examination (i.e., inspection, percussion, palpation, and auscultation) shall be performed during the course of the study.

  8. Change in heart rate from baseline up to end of study

    Time frame: Up to 10 days

    Heart rate shall be measured using standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period.

  9. 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

    Time frame: Up to 10 days

    QTcB shall be determined using standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. The QTcB interval is the QT interval corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate).

  10. 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

    Time frame: Up to 10 days

    QTcF shall be determined using standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. The QTcF interval is the QT interval corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate).

  11. Number of treatment-emergent electrocardiogram abnormalities up to end of study

    Time frame: Up to 10 days

    Electrocardiogram abnormalities shall be determined using standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period.

Secondary outcomes

  1. Maximum plasma concentration (Cmax) of ACT-128800

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis shall be taken immediately prior to dosing with ACT-128800 and at 0.5, 1, 1.5, 2.5, 4, 6, 10, 16, 24, 36, 48, 72, 96, 120 and 144 hours after dosing. Cmax will be calculated on the basis of the blood sampling time points.

  2. Time to maximum plasma concentration (tmax) of ACT-128800

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis shall be taken immediately prior to dosing with ACT-128800 and at 0.5, 1, 1.5, 2.5, 4, 6, 10, 16, 24, 36, 48, 72, 96, 120 and 144 hours after dosing. tmax will be calculated on the basis of the blood sampling time points.

  3. Area under the plasma concentration-time curve (AUC(0-t)) of ACT-128800

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis shall be taken immediately prior to dosing with ACT-128800 and at 0.5, 1, 1.5, 2.5, 4, 6, 10, 16, 24, 36, 48, 72, 96, 120 and 144 hours after dosing. AUC(0-t) shall be calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification

  4. Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-128800

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis shall be taken immediately prior to dosing with ACT-128800 and at 0.5, 1, 1.5, 2.5, 4, 6, 10, 16, 24, 36, 48, 72, 96, 120 and 144 hours after dosing. AUC(0-infinity) will be calculated by combining AUC(0-t) and AUC(extra). AUC(extra) represents an extrapolated value obtained by Ct/λZ, where Ct is the last plasma concentration measured above the limit of quantification and λZ represents the terminal elimination rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.

  5. Plasma half life (t1/2) of ACT-128800

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis shall be taken immediately prior to dosing with ACT-128800 and at 0.5, 1, 1.5, 2.5, 4, 6, 10, 16, 24, 36, 48, 72, 96, 120 and 144 hours after dosing. t1/2 will be calculated on the basis of the blood sampling time points.

  6. Change in lymphocyte count from baseline up to end of study

    Time frame: Up to 10 days

    At various time points up to the end of study about 3 mL of blood will be collected by venepuncture in the supine position, for the measurement of lymphocyte count.

Sponsors and collaborators

Lead sponsor

Actelion

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2009
Study completion
2009
First posted
Aug 22, 2014
Registry last updated
Aug 22, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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