Dual Orexin Antagonism and Emotion and Affective Processing Study

Exclusion Criteria26

• History of, receiving or seeking treatment for any sleep or circadian rhythm disorder or positive in screening questionnaires.
• History of, receiving or seeking treatment for any clinically significant mental health condition (including but not limited to schizophrenia, psychosis, bipolar affective disorder, major depressive disorder, obsessive compulsive disorder, post-traumatic stress disorder) or positive in screening questionnaires.
• History of, or current medical condition(s) which might increase the risk of oral administration of daridorexant, including:
• ADHD requiring treatment with stimulants or other centrally-acting drugs
• Neurological problems, including traumatic brain injury, epilepsy, Central Nervous System tumours or other severe neurological problems (e.g. Parkinson's disease; blackouts requiring hospitalisation)
• Current Asthma, Chronic Obstructive Pulmonary Disease, emphysema or any medical condition that affects the lungs or breathing
• Mild to severe hepatic impairment (Child-Pugh class A-C)
• Severe renal disease
• Severe gastrointestinal problems
• History of, or current medical condition(s) which, in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study
• Pregnancy (as determined by urine pregnancy test taken during screening visit), intention to become pregnant or breastfeeding during the study or over the following six months.
• Body mass index (BMI) below 18 or above 30kg/m2.
• Current or past history of drug or alcohol dependency.
• Regular alcohol consumption of more than 21 units per week or use of recreational drugs or performance-enhancing drugs (e.g. cannabis, cocaine, amphetamines) within past three months.
• Excessive caffeine consumption, i.e., consumption higher than 400mg a day of caffeine. This corresponds to more than 4 cups of brewed coffee, 6 espressos or filtered coffees, 9 cups of black tea, 10 cans of cola, or two "energy shot" drinks.
• Smoking more than 5 cigarettes per day (or other nicotine replacement equivalent, including vaping on average more than 50 puffs a day).
• Current or recent (past two months) use of any medication or medical devices (e.g. implanted neurostimulator) that affect brain function for the exception of contraceptives (pill, the Depo-Provera injection or the progesterone implant). This includes drugs that cause sedation (e.g. benzodiazepines, opioids, tricyclic antidepressants or sedative antipsychotics) or antihistamines.
• Current use of any medications at risk of interaction with daridorexant; in particular:
• strong or moderate CYP3A inhibitors (e.g. strong inhibitors - itraconazole, clarithromycin, ritonavir, grapefruit juice; moderate inhibitors - fluconazole, verapamil, diltiazem, erythromycin, ciprofloxacin, cyclosporine)
• strong or moderate CYP3A inducers (e.g. of strong inducers - rifampicin, carbamazepine, St. John's wort; moderate inducers - bosentan, efavirenz, etravirine, modafinil)
• Gastric pH-modifiers (e.g. famotidine and proton pump inhibitors such as omeprazole)
• P-gp transporters (e.g. dabigatran, digoxin)
• Inability to ingest up to 95mg of lactose.
• Previous participation in any other drug study or sleep intervention study in the last three months.
• Previous participation in any other study by the Psychopharmacology and Emotion Research lab (Department of Psychiatry, University of Oxford) or which uses the same computer tasks in the last 6 months
• Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.