Double-blind, placebo-controlled, randomized study to investigate the tolerability, safety, pharmacokinetics, and pharmacodynamics of ACT-541468: Part A: Multiple-ascending doses in healthy young adults after morning administration. Part B: Single-ascending doses in healthy elderly subjects after morning administration. Part C: Repeated doses in both healthy young adults and elderly subjects after evening administration.

Completed

Conditions: Sleeping disorders
insomnia
sleeping disorder

Registration Number: NL-OMON42430

Lead Sponsor: Actelion Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 84

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 < 1% per year, be sexually inactive, or have a vasectomized partner. (Details about reliable contraceptive measures only to be given in the core protocol (not in the protocol outline)).
- No clinically significant findings on the physical examination at screening.
- Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at screening.
- Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on the dominant arm, after 5 min in the supine position at screening.
- Elderly: SBP 100-160 mmHg, diastolic blood pressure (DBP) 50-95 mmHg, and pulse rate 45-100 bpm (inclusive), measured on the dominant arm, after 5 min in the supine position at screening.
- 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
- Hematology, coagulation, 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 at screening.
- 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 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 < 0 at screening or history of narcolepsy or cataplexy.
- 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.;Elderly only:
- Previous chronic treatment with any medication that is not given in stable doses and/or stable regimen within 2 months prior to screening.
- Previous treatment with central nervous system (CNS)-active drugs within 2 months prior to screening.
- Treatment with inhibitors of cytochrome P450 (CYP) 3A4 (e.g., azole derivatives, ritonavir, clarithromycin) from 2 weeks prior to screening visit and up to EOS.