Drug-Drug interaction, M1 agonist, Alzheimer, donepezil
Conditions
Interventions
HTL0018318 will be administered in a oral solution.
Sponsors
Heptares Therapeutics Ltd.
Eligibility
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 < 1% per year), be sexually inactive, or have a vasectomised partner; otherwise women not of childbearing potential who are defined as postmenopausal (i.e., amenorrhea for at least 1 year without an alternative medical cause), or surgically or naturally sterile; 6. If a male subject; must consent to and 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 spermicide), be sexually inactive, or have a sterilised partner; 7. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: Subjects must meet none of the following exclusion criteria at screening: 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 subjec
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. PK | — |
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 | — |
Contacts
Public ContactCentre for Human Drug Research
Zernikedreef 8
Outcome results
None listed