Alzheimer's Disease Nervous System Diseases Alzheimer's Disease
Conditions
Interventions
Part A of the study assisted dose-finding for Part B of the trial. Start and end dates of Part B lead directly on from the end of Part A. The three dose levels of 13.5, 40 and 79.5 mg HTL0009936 and t
intravenous for 30 minutes at 20 mL/h
2. HTL0009936 1 mg
intravenous for 30 minutes at 20 mL/h
3. HTL0009936 10 mg
intravenous for 30 minutes at 33.2 mL/h
4. HTL0009936 49.2 mg
intravenous
14.1 mg HTL0009936 for 30 min at 47 mL/h and 35.1 mg HTL0009936 for 4.5 h at 13 mL/h
5. HTL0009936 8
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Age
65 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Aged 65+ years 2. Blood pressure =140/90 mmHg at screening 3. Heart rate between 45 and 100 bpm at screening
Exclusion criteria
Exclusion criteria: 1. Use of antihypertensive drugs prior to and during the study period 2. Consumption of alcohol and caffeine-containing products, use of nicotine-containing products, and use of drugs influencing CYP3A4 and CYP2D6 activity prior to and during the study 3. Poor or ultra-rapid CYP2D6 metabolizer discovered on genotype screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety assessed by monitoring and recording of adverse events (AEs), vital signs, ECG, 5-hour Holter monitoring, and safety chemistry and hematology blood sampling (9 to 15 times) within the first 8 hrs after starting the administration, at 12 and 24 hrs post-dose in parts A and B, and between 7 and 11 days post-dose in Part B. 2. Pharmacokinetics of HTL0009936 assessed through continuous urine collection. PK blood samples were collected according to the same schedule pre-dose (9 to 15 times) within the first 8 hrs after starting the administration, at 12 and 24 hrs post-dose in parts A and B, and between 7 and 11 days post-dose in Part B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic oucomes in Part B 1. Vital signs assessed by systolic and diastolic blood pressure and pulse measurements taken after a minimum of 5 minutes rest in the supine position using an automatic oscillometric device at -28 days, pre-dose, 9 to 15 times within the first 8 h after starting the administration, at 12 and 24 h post-dose, and between 7 and 11 days post-dose. 2. Cognitive and neurophysiological functioning (NeuroCart and the Cambridge Neuropsychological Test Automated Battery (CANTAB) assessments at baseline (pre-dose) and between 1 h and 8 h post-treatment). Tests include: 2.1. Pupillometry at -28 days, pre-dose, and at 1, 3.5, 7.5 and 23.5 h after dosing 2.2. Milner Maze test at -28 days, pre-dose, and at 1, 3.5, 7.5 and 23.5 h after dosing 2.3. MMN at -28 days, pre-dose, and at 1.5, 4, and 8 h after dosing 2.4. VAS Nausea at -28 days, pre-dose, and at 1, 3.5, 7.5 and 23.5 h after dosing 2.5. N-back test at -28 days, pre-dose, and at 1, 3.5, 7.5 and 23.5 h after dosing 2.6. Adaptive tracking test at -28 days, pre-dose, and at 1, 3.5, 7.5 and 23.5 h after dosing 2.7. P300 at -28 days, pre-dose, and 1.5, 4, and 8 h after dosing 2.8. Pharmaco-electroencephalography (p-EEG) at -28 days, pre-dose, and at 1.5, 4, and 8 h after dosing 2.9. Leeds Sleep Questionnaire at pre-dose and 23.5 hrs after dosing 2.10. Paired Associates Learning (PAL) test assessed up to -28 days, pre-dose, and 5 and 24 h post-dosing 2.11. Rapid Visual Information Processing (RVIP) test assessed up to -28 days, pre-dose, and 5 and 24 h post-dosing 2.12. Spatial Working Memory (SWM) test assessed up to -28 days, pre-dose, and 5 and 24 h post-dosing 2.13. VVLT assessed up to -28 days and at 4 h after dosing | — |
Countries
Netherlands
Outcome results
None listed