Sleeping disorders insomnia sleeping disorder
Conditions
Interventions
Part A: Oral doses of ACT 541468 will be administered in the morning of Day 1
to Day 5 after 10 hours of fasting. The starting dose will be 10 mg. Foreseen
additional dose levels are 25 mg and 75 mg
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 and female subjects aged between 18 and 45 years (inclusive) at screening. - Elderly (part B and C only): Healthy male and female subjects aged between 65 and 80 years (inclusive) at screening. - Subjects must have a regular sleep pattern of at least 6 hours nocturnal sleep. - Women must have a negative serum pregnancy test at screening and a negative urine pregnancy test predose on Day 1. Women of childbearing potential must consistently and correctly use (from screening, during the entire study, and for at least 90 days after last study drug intake) a reliable method of contraception with a failure rate of
Exclusion criteria
Exclusion criteria: - Pregnant or lactating women. - Known hypersensitivity to the drug or drugs of the same class, or any of their excipients of the drug formulation. - Previous exposure to the study medication. - 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 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 End-of-Study [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. - 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, med¡an, maximum, standard deviation (SD), standard error (SE), and 95% confidence interval (Cl) of the mean. Part A, Day 1 and 5 Pharmacokinetic variables of ACT-541468 that will be analyzed are: maximum plasma concentration (Cmax), time to reach Cmax (tmax), terminal half-life (t1/2), area under the plasma concentration-time curve from zero to 8 h after study drug administration (AUC0-8), area under the plasma concentration-time curve during a dosing interval (AUC0-24). Part A, Day 5 Pharmacokinetic variables of ACT-541468 that will be analyzed are: area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC0-*), t1/2, dose proportionality, and the accumulation index (AI). Part B Cmax, tmax, t1/2, AUC0-8, AUC0-24, AUC0 t, AUC0-*, dose proportionality. Part C Trough concentrations of study drug on the evening of Day 1, Day 3, Day 5, and Day 7. Plasma concentrations of study drug in the morning on Day 2, Day 4, Day 6, and Day 8 (i.e., 8 hours after study drug administration). Pharmacodynamic end points: Part A Change from baseline to each time point of measurement for the following assessments that will be performed on Day 1 and 5: - Saccadic peak velocity. - Body sway (antero-posterior sway in mm/2 min). - Adaptive tracking performance. - Visual Analog Scales according to Bond and Lader for subjective alertness, mood, and calmness. - Narcolepsy Questionnaire(s). - Karolinska Sleepiness Scale (KSS) to assess subjective sleepiness. - VAS Bowdle for subjective psychedelic effects. Part B Change from baseline to each time point of measurement for the following assessments: - Saccadic | — |
Secondary
| Measure | Time frame |
|---|---|
| n.a. | — |
Countries
Netherlands
Outcome results
None listed