A three part, randomised, double-blind, placebo-controlled single ascending dose study to assess safety, pharmacokinetics and pharmacodynamics of oral HTL0018318 in healthy younger adult elderly subjects.

Completed

• Conditions: Schizofrenie; Alzheimer's disease; dementia & schizophrenia; 10012272

• Registration Number: NL-OMON42509
• Lead Sponsor: Heptares Therapeutics Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 72

Inclusion Criteria

1. Healthy male 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;
2. BMI between 18 and 34 kg/m2, inclusive;
3. Ability to communicate well with the investigator in the Dutch language;
4. Able to participate and willing to give written informed consent and to comply with the study restrictions;
5. Willing and able to perform the cognitive tests, as evidenced by performance on the training session of the cognitive tests;
Part 1 and 2 (healthy younger adult male subjects);
• Age 18 to 55 years, inclusive.
Part 3 (healthy elderly male and female subjects);
• Age >=65 years, inclusive.
• Woman should be post-menopausal or naturally infertile.

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. A history of any chronic respiratory problems such as asthma, recurrent chest infections, COPD;
4. A history of epilepsy or seizures of any kind at any time;
5. Any disease associated with cognitive impairment, including but not limited to schizophrenia and dementia;
6. 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;
7. 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;
8. Notable resting bradycardia (HR < 45 bpm) or tachycardia (HR > 100 bpm) at screening or baseline visit;
9. A QTcF > 450 or < 300 msec at resting ECG at screening or baseline visit;
10. Personal or family history of congenital long QT syndrome or sudden death;
11. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening;
12. Aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin levels >1.5 times the upper limit of normal at screening;
13. Evidence of significant renal insufficiency, indicated by a glomerular filtration rate lower than the lower limit of normal (related to age) at screening;
14. 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);
15. Use of tobacco and/or nicotine-containing products within 90 days of dosing;
16. 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;
17. Positive urine drug screen (UDS) or alcohol or cotinine test at screening and/or pre-dose;
18. Intake of any food or any drinks containing cranberry, po

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability endpoints<br /><br>- Treatment-emergent (serious) adverse events ((S)AEs)<br /><br>- Concomitant medication<br /><br>- Clinical laboratory tests (Haematology, Chemistry, Urinalysis)<br /><br>- Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic<br /><br>blood pressure (mmHg))<br /><br>- Electrocardiogram (ECG) (Heart Rate (HR) (bpm), PR, QRS, QT, QTcF)<br /><br><br /><br>Pharmacokinetics<br /><br>A population approach PK model will be developed, describing the plasma<br /><br>HTL0009936 concentrations over time.<br /><br><br /><br>Pharmacodynamics (Part 1 and 3 only)<br /><br>Adaptive Tracking test<br /><br>Visual Analogue Scale<br /><br>N-back test<br /><br>Milner MAZE test<br /><br>Pupil size<br /><br>EEG/ERP</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To assess the concentration of HTL0018318 in CSF.<br /><br>- To undertake preliminary investigations into the metabolite(s) of HTL0018318<br /><br>in selected and/or pooled samples.</p><br>