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

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ClinicalTrials.gov Identifier: NCT02223832
Recruitment Status : Completed
First Posted : August 22, 2014
Last Update Posted : August 22, 2014
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE August 21, 2014
First Posted Date  ICMJE August 22, 2014
Last Update Posted Date August 22, 2014
Study Start Date  ICMJE February 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2014)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2014)
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE Healthy
Intervention  ICMJE Drug: ACT-128800
Study Arms  ICMJE Experimental: ACT-128800

A single oral dose of 40 mg ACT-128800 will be administered as

1 capsule given in the fasted state in the morning

Intervention: Drug: ACT-128800
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 21, 2014)
20
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02223832
Other Study ID Numbers  ICMJE AC-058-107
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Patrick Brossard, PhD Actelion Pharmaceuticals Limited
PRS Account Actelion
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP