Schizofrenie, Neurodegenerative disorders Alzheimer's disease dementia & schizophrenia
Conditions
Interventions
In this study HTL0018318 will be administered in a oral solution.
Sponsors
Heptares Therapeutics Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Young adults: age 18-55 inclusive. Elderly adults: age *65 years, inclusive. 2. Healthy young and elderly male and female subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis; 3. BMI between 18 and 34 kg/m2, inclusive; 4. Ability to communicate well with the investigator in the Dutch language; 5. Young female subjects (18-55 years inclusive) must have a negative serum pregnancy test at screening and urine pregnancy test pre-dose 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) double barrier contraception (a condom combined with a method of contraception with a failure rate of
Exclusion criteria
Exclusion criteria: 1. Legal incapacity or inability to understand or comply with the requirements of the study; 2. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history taking and physical examinations obtained during the screening visit and/or at the start of the first study day for each period as judged by the investigator (including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder); 3. Any disease associated with cognitive impairment, including but not limited to schizophrenia and dementia; 4. Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), electrocardiogram (ECG) and vital signs, or physical findings at screening and/or at the start of the first study day for each period (as judged by the investigator). In case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects; 5. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg or a history of a significant period of hypertension as judged by the principal investigator; 6. Notable resting bradycardia (HR 100 bpm) at screening or baseline visit; 7. A QTcF > 450 or 1.5 times the upper limit of normal at screening; 11. Evidence of significant renal insufficiency, indicated by a glomerular filtration rate lower than the lower limit of normal (related to age) at screening; 12. Presence or history (within 3 months of screening) of alcohol abuse confirmed by medical history, or daily alcohol consumption exceeding 2 standard drinks per day on average for females or exceeding 3 standard drinks per day on average for males (1 standard drink = 10 grams of alcohol), or a positive breath alcohol test at screening or upon admission to the Clinical Research Unit (CRU), and the inability to refrain from alcohol use from 24 hours before screening, dosing and each scheduled visit until discharge from the clinical research unit (CRU) (alcohol consumption will be prohibited during study confinement) 13. Use of tobacco and/or nicotine-containing products within 90 days of dosing; 14. Habitual and heavy consumption of caffeinated beverages (more than 8 cups of coffee or equivalent/day) at screening and/or unable to refrain from use of (methyl) xanthine (e.g. coffee, tea, cola, chocolate) from 24 hours prior to dosing until discharge from the CRU; 15. Positive urine drug screen (UDS), serum/urine pregnancy test for females of child-bearing potential or alcohol or cotinine test at screening and/or pre-dose; 16. Concomitant use of drugs that are inhibitors/inducers of CYP3A4 (e.g., ketoconazole, ritonavir) from 21 days prior to study drug administration; 17. Concomitant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -Treatment-emergent (serious) adverse events ((S)AEs) until the end of study (EOS) visit. -Treatment-emergent abnormalities in vital signs (e.g. blood pressure and pulse rate) until the end of study (EOS) visit. -Treatment-emergent marked ECG abnormalities until the end of study (EOS) visit. -Treatment-emergent marked laboratory abnormalities until the end of study (EOS) visit. -Concomitant medication -Salivary measurement -Respiratory function measurement -NeuroCart assessments: *Adaptive Tracking test *Milner Maze test (immediate, delayed and reversed condition) *N-back test (0-back, 1-back and 2-back condition) *Pupillometry *Electroencephalography (EEG): 21-lead EEG recordings; standard power spectrum analysis (optional: EEG analysis by NBT analytics) *Event related potentials (ERPs) (i.e., P300 and mismatch-negativity (MMN) tasks) *Visual Analogue Scales according to Bond and Lader (alertness, mood, calmness) and for nausea. - Leeds sleep evaluation questionnaire | — |
Secondary
| Measure | Time frame |
|---|---|
| n.a. | — |
Countries
Netherlands
Outcome results
None listed