fMRI-behavioral Study of Cholinergic Augmentation With Donepezil in Healthy Sleep Deprived Adults

Exclusion criteria

• . The subject has taken prohibited medication within 1 week (or 14 days if the drug is a potential enzyme inducer) or within 5 half-lives prior to first dosing for any medication ingested, whichever is longer) prior to first dosing, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study procedures or compromise safety. Prohibited medication is any prescribed medication or over-the-counter (OTC) medication, including high-dose vitamins or dietary supplements, or any herbal medicine known to interfere with the metabolic CYP pathways, (e.g. St. John's Wort) or cognitive function (e.g. ginko). Paracetamol for mild analgesia will be permitted.
• . The subject has a significant history of drug or alcohol abuse, defined as an alcohol intake greater than 21 units per week or a history of drug abuse within the last 6 months, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 250 mL of lager/beer, 100 mL of Wine, or 25 mL of spirits.
• . The subject has an orthostatic blood pressure reduction \>20 mmHg (based on the difference of systolic blood pressure between supine and after standing for 1 minute).
• . The subject has been exposed to more than 3 new chemical entities (NCEs) within 12 months prior to the first dosing day, or participated in a trial with any drug within 84 days before the start of the study, or participated in a trial with a NCE within 112 days before the start of the study.
• . History or presence of hypersensitivity to the study drugs or drugs of this class (hyoscine, atropine, donepezil) or a history of other severe drug allergy or hypersensitivity which, in the opinion of the physician responsible, contraindicates their participation.
• . The subject has a serious illness, such as liver or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• . The subject has history or presence of peptic ulcer disease, cardiac arrhythmias, cardiac conduction abnormalities, asthma or obstructive pulmonary disease.
• . The subject has history or presence of psychiatric or neurological illness, obstructive sleep apnea, narcolepsy or periodic leg movements as ascertained by questionnaire.