Schizophrenia Alzheimer's disease dementia & schizophrenia
Conditions
Interventions
Sponsors
Heptares Therapeutics Ltd.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Elderly male or female subjects aged between 65 and 80 (inclusive) years old; 2. Healthy subjects as defined by the absence of evidence of any active or chronic disease following detailed medical and surgical history review and 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. Able to understand the commitments of the study and to communicate effectively with the investigator and site staff; 5. If a woman of childbearing potential; must consent to and 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 from the medical history review and the 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 (including history of ulcer disease or gastrointestinal bleeding), hepatic, or renal disorder). 3. A recent ( 100 bpm) at screening or baseline visit. 11. A QTcF > 450 (for males) or >460 (for females) or < 300 msec at resting ECG at screening and baseline visit. 12. Personal or family history of congenital long QT syndrome, *sick sinus syndrome* or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block or sudden death. 13. Based on the results of the 24 hour period ECG Holter monitoring during screening, potential subjects can be excluded based on the following exclusion criteria: more than 200 ventricular ectopics in 24 hours. Ventricular tachycardia (defined as being three or more successive ventricular ectopic beats at a rate of at least 120 beats per min). Second degree heart block. Sustained cardiac arrhythmias (atrial fibrillation, SVT, complete heart block). Any symptomatic arrhythmia (except isolated extra systoles). 14. 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. 15. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability/safety endpoints - Treatment-emergent (serious) adverse events ((S)AEs) - Concomitant medication - Clinical laboratory tests o Haematology o Chemistry o Urinalysis - Vital signs o Pulse Rate (bpm) o Systolic blood pressure (mmHg) o Diastolic blood pressure (mmHg) - Electrocardiogram (ECG) o Heart Rate (HR) (bpm), PR, QRS, QT, QTcF - Holter 24 hours Pharmacokinetic endpoints Pharmacokinetics by non-compartmental analysis: Plasma and urine PK analysis of HTL0018318 Day 20 (and 45) to 27 (52); Cmax, Tmax, Ctrough, AUC (0-t, 0-tau, 0-infinity), *z, half-life, CLp/F and Vd/F, renal clearance and amount excreted in urine. Plasma PK analysis of donepezil (parameters as described for HTL0018318) at steady state (Day 19) and in combination with HTL0018318 (Day 20 to 24). Bank samples for genotyping will be collected for post hoc analysis if deemed necessary to interpret better the pharmacokinetic data. Metabolite profiling may be undertaken on selected or pooled samples, and reported separately. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic endpoints - Visual Analog Scales (VAS) according to Bond and Lader to assess: o mood (mm) o alertness (mm) o calmness (mm) - VAS nausea (mm) - Salivary measurement (g) - Respiratory function o Forced vital capacity (FVC) o Volume forcedly expired in 1 second (FEV1) o Peak Expiratory Flow (PEF) in litres per second - Leeds Sleep Evaluation Questionnaire (LSEQ): o Getting to sleep (GTS) (mm) o Quality of sleep (QOS) (mm) o Awake following sleep (AFS) (mm) o Behaviour following wakening (BFW) (mm) - Assessment of heart rate variability | — |
Countries
The Netherlands
Outcome results
None listed