Evaluation of the pharmacodynamic and pharmacokinetic effects of multiple doses of ACT-078573 on the pharmacokinetics of a single dose of desipramine
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic variables/outcomes:
• Maximum concentration (Cmax) of desipramine
• Area under the plasma concentration-time curve from zero to infinity (AUC0-*)
of desipramine
Secondary outcome
Pharmacokinetic variables/outcomes:
• Maximum concentratie (Cmax) of the metabolite 2-OH desipramine
• Area under the plasma concentration-time curve from zero to infinity (AUC0-*)
of the metabolite 2-OH desipramine
• Time to reach Cmax (tmax) of desipramine (and the metabolite 2-OH
desipramine).
• Area under the plasma concentration-time curve from zero to time t of the
last measured concentration above the quantificationlimit (AUC0 t) of
desipramine (and the metabolite 2-OH desipramine).
• The halflife (t*) of desipramine (and the metabolite 2-OH desipramine).
• Maximum concentration (Cmax) of ACT 078573.
• Area under the plasma concentration-time curve from zero to 24 hours
(AUC0-24) of ACT 078573.
• Time to reach Cmax (tmax) of ACT 078573.
Pharmacodynamic outcomes/variables:
Eye Movements:
• Saccadic peak velocity
Adaptive tracking:
• Adaptive tracking performance
Body Sway
Pupillometry:
• Pupil / iris ratio
Visual analog scale (VAS) Bond & Lader:
• Alertness
• Mood
• Calmness
Background summary
ACT-078573 is a selective orally active orexine-antagonist. Orexine peptiden
play a central role in het sleep-wake rhythm. Preclinical data have shown that
this compound increased the REM and non-REM sleep in animal models. Earlier
phase I research in healthy volunteers has brought no serious side effects to
light.
ACT-078573 is being developed for the treatment of insomnia. Earlier
preclinical research has shown that this compound can inhibit CYP2D6 in vitro.
Drug-drug interaction studies are therefore needed to determine the clinical
relevance of this. Desipramine was chosen because this drug is also a substrate
for CYP2D6
Study objective
Evaluation of the pharmacodynamic and pharmacokinetic effects of multiple doses
of ACT-078573 on the pharmacokinetics of a single dose of desipramine
Study design
A single-center, randomized, placebo-controlled, two-way cross-over study to
determine drug-drug interaction on the farmacokinetics and farmacodynamics of
ACT-078573 and a single dose of desipramine in healthy male volunteers
Study burden and risks
Possible side effects of study medication
ACT-078573
For ACT-078573 the most common side effects reported to date are tiredness,
dizziness, disturbed concentration, and headache.
Double vision, nausea and muscle weakness (during emotional moments or at
waking up) have been reported a few times. These symptoms may be frightening
for persons not familiar with them. Other healthy volunteers have reported dry
or irritated eyes after multiple doses.
Desipramine
The most common side effects include problems to focus on close objects,
constipation, tiredness, dry mouth and low blood pressure.
In rare occasions sleep disorders and related tiredness, urinary dysfunction,
restlessness, thirst, exanthema, allergies and sexual function disorders may
occur.
Gewerbestrasse 16
CH-4123 Allschwil
Zwitserland
Gewerbestrasse 16
CH-4123 Allschwil
Zwitserland
Listed location countries
Age
Inclusion criteria
Signed informed consent prior to any study-mandated procedure.;Male aged between 18 and 45 years (inclusive) at screening.;CYP2D6 extensive metabolizer (EM) genotype.;No clinically significant findings on the physical examination at screening.;Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) at screening.;Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP)
50-90 mmHg, and heart rate (HR) 45-90 bpm (all inclusive), measured at screening on the leading arm after 5 minutes in the supine position.;12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening and meeting the following criteria: QTcB interval * 430 msec, QRS interval * 110 msec, and PR interval * 220 msec.;Hematology and clinical chemistry 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
History of cardiovascular disease (e.g., arrhythmia, congenital long QT syndrome).;History of seizures disorders.;Clinically significant findings at baseline assessments for pupillometry.;Any contraindication to desipramine or any tricyclic antidepressant (TCA).;Known hypersensitivity to desipramine, or any TCA, Ponceau 4R, or any other excipients of the drug formulations.;Treatment with any prescribed or OTC medications (including herbal medicines such as St John*s Wort) within 2 weeks prior to screening.;Treatment with another investigational drug within 3 months prior to screening or more than 4 times within the year prior to screening.;History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.;Excessive caffeine consumption (more than 800 mg per day) at 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.;Smoking within 3 months prior to screening and inability to refrain from smoking during the course of study.;Loss of 250 mL or more of blood within 3 months prior to screening.;Positive hepatitis serology, except for vaccinated subjects, at screening.;Positive HIV 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-001607-35-NL |
| CCMO | NL23235.058.08 |