Healthy Subjects Clinical Trial
Official title:
A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-389949 in Healthy Subjects
NCT number | NCT02099201 |
Other study ID # | AC-073-102 |
Secondary ID | |
Status | Completed |
Phase | Phase 1 |
First received | |
Last updated | |
Start date | November 2012 |
Est. completion date | May 2013 |
Verified date | July 2018 |
Source | Idorsia Pharmaceuticals Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a single-center, double-blind, parallel-group, randomized, placebo-controlled,
multiple-ascending oral dose study to investigate the safety, tolerability, pharmacokinetics,
and pharmacodynamics of ACT-389949 in healthy subjects.
Part A of the study will evaluate the safety and tolerability following once a day oral
dosing of ACT-389949 for 9 days and investigate ACT-389949 pharmacokinetics and
pharmacodynamics.
Part B of the study will evaluate the safety and tolerability of ACT-389949 following a
maximum of two different oral dosing regimens: ACT-389949 given either every 3 days for 13
days or every 2 days for 9 days (5 doses for each regimen).
Part C of the study, if required, will provide additional information to that obtained from
Parts A and B in terms of safety, tolerability, pharmacokinetics, and pharmacodynamics of
ACT-389949.
Status | Completed |
Enrollment | 65 |
Est. completion date | May 2013 |
Est. primary completion date | May 2013 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: - Signed informed consent in local language. - Healthy Caucasian male subjects and female subjects of non-childbearing potential. - Men with female partners of childbearing potential must agree to use 2 reliable methods of contraception from first drug administration up to a minimum of 90 days after the end of treatment. - Male subjects must agree not to donate sperm from the first drug administration until 90 days after the end of treatment. - Non-smokers, defined as never smoked or achieved cessation = 12 months prior to screening. - Body mass index of 18.0 to 28.0 kg/m^2 (inclusive) at screening. - No clinically significant findings on the physical examination at screening. - Negative results from urine alcohol and drug screen at screening and on Day -1. - Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive) measured at screening. - 12-Lead electrocardiogram without clinically relevant abnormalities at screening. - Body temperature 35.5-37.7 °C at screening and prior to first dosing. - C-reactive protein (CRP) and total and differential white blood cell (WBC)count within the local laboratory normal ranges at screening and on Day -1. - Hematology, coagulation, clinical chemistry, and urinalysis results (other than total differential WBC and CRP), not deviating to a clinically relevant extent from the normal local laboratory range(s) at screening. - Forced expiratory volume in 1 second (FEV1) = 80% of predicted, FEV1 / Forced vital capacity = 70%. - Subjects must be able to provide adequate sputum following induction with hypertonic saline at screening. - Able to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study. - Able to stay in the unit for the entire duration required and undertake all study related procedures. Exclusion Criteria: - Circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. - 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 fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions. - Veins unsuitable for intravenous puncture on either arm. - Loss of 250 mL or more of blood or blood donation, within 3 months prior to screening. - Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s). - Previous exposure to ACT-389949. - Exposure to lipopolysaccharide within the last year. - Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 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. - Use of regular medication or therapy (including vaccines) or over-the-counter medications within 2 weeks prior to first study drug administration or 5 half-lives of the medication, whichever is longer. - 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. - Vaccinations within the previous 6 months or foreign travel to areas within the last 6 months where infectious diseases are prevalent. - Signs or symptoms suggestive of infection within 2 weeks prior to study screening and between screening and dosing. - Signs of respiratory tract infections within 2 weeks prior to screening and between screening and dosing. - History of atopic allergy. - Hay fever, if within active season. - Chronic diseases including those with recurring periods of flare-ups and remission. - Legal incapacity or limited legal capacity at screening. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Celerion | Belfast |
Lead Sponsor | Collaborator |
---|---|
Idorsia Pharmaceuticals Ltd. |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change from baseline up to end of study 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) | Up to 13 days | |
Primary | Change from baseline up to end of study 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) | Up to 13 days | |
Primary | Change from baseline up to end of study 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) | Up to 13 days | |
Primary | Change from baseline up to end of study in body temperature | Body temperature will be measured in the ear, where possible using the same thermometer(s) for all the subjects throughout the study. | Up to 13 days | |
Primary | Change from baseline up to end of study in body weight | Body weight will be measured where possible using the same weighing scale for all subjects throughout the study. The weighing scale should have a precision of at least 0.5 kg. | Up to 13 days | |
Primary | Change from baseline up to end of study in PQ/PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) | PQ/PR interval will be determined from standard 12-lead electrocardiogram (ECG) recorded in the supine position, after a 5-minute period of resting. | Up to 13 days | |
Primary | Change from baseline up to end of study in QRS duration (time interval from the beginning of the Q wave to the end of the S wave) | QRS duration will be determined from standard 12-lead ECG recorded in the supine position, after a 5-minute period of resting. | Up to 13 days | |
Primary | Change from baseline up to end of study in QT interval (time interval from beginning of the Q wave until end of the T wave) | QT interval will be determined from standard 12-lead ECG recorded in the supine position, after a 5-minute period of resting. | Up to 13 days | |
Primary | Change from baseline up to end of study in QTcB interval according to Bazett's correction (QTcB) | QTcB interval will be determined from standard 12-lead ECG recorded in the supine position, after a 5-minute period of resting. 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) | Up to 13 days | |
Primary | Change from baseline up to end of study in QTcF interval according to Fridericia's correction (QTcF) | QTcF interval will be determined from standard 12-lead ECG recorded in the supine position, after a 5-minute period of resting. The QTcB interval is the QT interval corrected for heart rate with Fridericia's formula (QTcB = QT/RR^0.33 where RR is 60/heart rate) | Up to 13 days | |
Primary | Frequency of treatment-emergent ECG abnormalities from baseline up to end of study | Treatment-emergent abnormalities will be determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting. | Up to 13 days | |
Secondary | Area under the plasma concentration-time curve of ACT-389949 during the dosing interval (AUCt,Dayx) | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. AUCt,Dayx will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the lower limit of quantification during the dosing interval. | Up to 13 days | |
Secondary | Maximum plasma ACT-389949 concentration during the dosing interval (Cmax,Dayx) | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. Cmax,Dayx will be calculated on the basis of the blood sampling time points. | Up to 13 days | |
Secondary | Average plasma ACT-389949 concentration during the dosing interval (Cav,Dayx) | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. Cav,Dayx will be calculated by dividing AUCt,Dayx by the dosing interval. | Up to 13 days | |
Secondary | Time to reach maximum plasma ACT-389949 concentration (tmax,Dayx) | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. tmax,Dayx will be calculated on the basis of the blood sampling time points. | Up to 13 days | |
Secondary | Accumulation index (AI) of ACT-389949 | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. The AI will be calculated as follows: AUCtDayx / AUCtDay1. | Up to 13 days | |
Secondary | Trough concentration (Ctrough,Dayx) of ACT-389949 | Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at various time points after dosing. Ctrough,Dayx of ACT-389949 will be taken directly from the measured plasma concentration-time values. | Up to 13 days |
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