Sleep disorders insomnia Sleeping disorders
Conditions
Interventions
At each dose level, six subjects will receive a single oral dose of ACT-541468
(formulation A) and two subjects will receive a single oral dose of matching
placebo.
For the biocomparison part in th
Sponsors
Actelion Pharmaceuticals
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Signed informed consent in the local language prior to any study-mandated procedure. • Healthy male subjects aged between 18 and 45 years (inclusive) at screening. • Hematology, clinical chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening. • No clinically significant findings on physical examination at screening. • Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening. • Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive) measured at screening on the dominant arm after 5 min in supine position. • 12-lead ECG without clinically relevant abnormalities in supine position at screening. • Negative results from alcohol breath test and urine drug screen at screening and at Day 1. • Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study. • Only for subjects in the mass balance and metabolism part (third dose group): subjects must have a regular (daily) defecation pattern.
Exclusion criteria
Exclusion criteria: • Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions. • Veins unsuitable for i.v. 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). • Treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St. John*s Wort) within 2 weeks prior to (first) study drug administration. • Treatment with another investigational drug within 3 months prior to screening or having participated 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. • 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 drugs (appendectomy and herniotomy allowed; cholecystectomy not allowed). • Excessive caffeine consumption, defined as >= 800 mg per day at screening. • Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study (from screening to EOS). • Loss of 250 ml or more of blood, or an equivalent amount of plasma, within 3 months prior to screening. • Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening. • Positive results from the HIV serology at screening. • Known hypersensitivity to any excipients of the drug formulations. • Modified Swiss Narcolepsy Scale total score
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Concentrations of ACT-541468 and its metabolites and radioactivity in whole blood and plasma per time point will be summarized by dose presenting number of observations, arithmetic mean, minimum, median, maximum, standard deviation (SD), standard error (SE), and 95% confidence interval (CI) of the mean. Dose proportionality will be assessed across ACT-541468 doses (formulation A) using the power model described by Gough et al., [Gough 1995] which will be applied to the loge AUC0-* and Cmax data. A point estimate and 90% CI will be determined for the population mean slope. Differences between formulation A (reference) and formulation B (test) for AUC0-8, AUC0-24, AUC0-t, AUC0-*, Cmax, Cu/C, and t* will be explored using the ratio of geometric means (absolute) and its 90% CI. Differences between formulation A and formulation B for tmax will be explored using the median difference and its 90% CI. • Individual absolute bioavailability will be listed by subject number and summarized overall presenting number of observations, arithmetic mean and its 95% CI, minimum, median, maximum, SD, and CV(%). • Absolute bioavailability (F) will be calculated using the geometric means of AUC0-* All PK parameters of 14C-labeled ACT-541468 (including CL, Vss, and cumulative excretion in urine and feces) will be presented as described above. If applicable, individual concentrations of ACT-541468 in urine will be listed per collection interval by dose and subject and summarized by dose presenting number of observations, arithmetic mean, minimum, median, maximum, SD, SE, CVb(%), and 95% CI of the means. Percentage of total dose excreted (unchanged and metabolized) in urine and CLR will be similarly listed and summarized with the exception that also the geometric mean and 95% CI will be provided. Individual PD data will be listed by dose, formulation, and subject. At each time point, absolute values and change from baseline of PD variables will be summarized with | — |
Countries
Netherlands
Outcome results
None listed