Healthy Subjects
Conditions
Keywords
Pharmacokinetics, Tolerability, Safety, ACT-129968
Brief summary
To explore the pharmacokinetics (PK) of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule and to evaluate the safety and tolerability of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule.
Detailed description
A total of 10 female and 10 male healthy subjects will be enrolled and will attend two treatment periods, separated by a 7-9 day washout. Over these two periods, two formulations of ACT-129968 (Treatment A: two capsules, 250 mg each; Treatment B: one tablet, 500 mg) will be administered in the sequence A/B or B/A to 10 subjects (5 females and 5 males) per sequence as determined by randomization.
Interventions
DRUGACT-129968 500 mg tablet
ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist
DRUGACT-129968 250 mg capsule
ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent in the local language prior to any study-mandated procedure. * Women must have * a negative serum pregnancy test at screening and * a negative urine pregnancy test pre-dose on Day-1 of each treatment period. * Women of childbearing potential must consistently and correctly use (from screening, during the entire study, and for at least 28 days after last study drug intake) a reliable method of contraception with a failure rate of \< 1% per year, be sexually inactive, or have a vasectomized partner. Women not of childbearing potential are defined as post-menopausal (i.e., spontaneous amenorrhea for at least 1 year without an alternative medical cause) or surgically or naturally sterile. * No clinically significant findings on the physical examination at screening. * Body mass index (BMI) of 18.0 to 28.0 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 on the dominant arm (dominant arm = writing arm) after 5 minutes in the supine position at screening. * 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 minutes in the supine position at screening. * Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening. * Negative results from urine drug screen and breath alcohol test at screening and on admission to the unit (Day-1) in Period 1 and Period 2. * Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
Exclusion criteria
* Pregnant or lactating women. * Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s). * 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 (appendectomy and herniotomy allowed, cholecystectomy not allowed). * Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions. * History or clinical evidence of allergic rhinitis or asthma. * Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture). * Previous exposure to the study medication. * Treatment with another investigational drug within 3 months prior to screening or participation 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, defined as 800 mg per day at screening. * Alcohol consumption of \> 21 units/week or \> 3 units/day. * Smoking within 3 months prior to screening. * Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to first study drug administration. * Loss of 250 mL or more of blood within 3 months prior to screening. * Positive results from the hepatitis serology (Hepatitis B surface antigen and anti-hepatitis C virus), except for vaccinated subjects or subjects with past but resolved hepatitis (defined as positive finding for antibodies but negative findings for antigens), 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t). | Up to 48 h in each treatment period (1 and 2) | The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles. |
| The area under the plasma concentration-time curve from zero to infinity (AUC0-infinity). | Up to 48 h in each treatment period (1 and 2) | The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles. |
| The maximum plasma concentration (Cmax) | Up to 48 h in each treatment period (1 and 2) | The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles. |
| The time to reach maximum plasma concentration (tmax) | Up to 48 h in each treatment period (1 and 2) | The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles. |
| The terminal elimination half-life (t½) | Up to 48 h in each treatment period (1 and 2) | The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to each time point of measurement during each treatment period and to EOS in pulse rate | Up to 13 days | bpm |
| Body weight at baseline and end of study visit | Up to 13 days | — |
| Change from baseline to each time point of measurement during each treatment period and to EOS in ECG variables | Up to 13 days | ECG variables are to be recorded at rest using a standard 12-lead ECG |
| Change from baseline to EOS for clinical chemistry | Up to 13 days | — |
| Number of patients with treatment-emergent physical examination abnormalities at EOS | Up to 13 days | — |
| Number of patients with treatment-emergent AEs and SAEs for each treatment period | from study drug administration on Day 1 up to 48 hours post-dose | — |
| Number of patients with AEs leading to premature discontinuation of study drug | Entire duration of study | — |
| Number of patients with treatment-emergent ECG abnormalities for each treatment period | from study drug administration on Day 1 up to 48 hours post-dose | — |
| Change from baseline to EOS for pregnancy serum test | Up to 13 days | — |
| Change from baseline to EOS for virus serology | Up to 13 days | — |
| Change from baseline to EOS for hematology | Up to 13 days | — |
| Change from baseline to each time point of measurement during each treatment period and to EOS in supine blood pressure | Up to 13 days | mmHg |
Countries
Germany
Outcome results
None listed