Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders.
Detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders. This study is a single ascending dose study.
Interventions
DRUGHTL0009936
Single dose
DRUGHTL0009936 placebo
Placebo single dose
Sponsors
Nxera Pharma UK Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Body mass index of ≥19 and ≤ 30kg/m² * Healthy subject free from any clinically significant illness or disease * Female subjects must be ≥65 years
Exclusion criteria
* Subject who is predicted to be a CYP2D6 poor or ultra rapid metabolizer * History of hypersensitivity to study drug * History of epilepsy or seizures * Subject with previous history of suicidal behavior * Subjects with significant hearing impairment * Subjects with an abnormal EEG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events, as a measure of safety and tolerability | From signing of informed consent up to 30 days after the final visit | AE reports include a description of the AE, date and time of onset and resolution, intensity, and relationship to IMP. |
| Changes in Safety Lab parameters as a measure of safety and tolerability | Screening, Day-1, at select dosing days, and at 5 to 7 days post dose for single doseand 15 to 17 days post first dose in multiple dosing. | Hematology, clinical chemistry, urinalysis |
| Changes in vital signs as a measure of safety and tolerability | Screening, Day-1, at select dosing days and at 5 to 7 days post dose for single dose, and 15 to 17 days post first dose in multiple dosing. | Pulse rate,body temperature,blood pressure, and orthostatic changes. |
| Changes in 12-lead electrocardiograms as a measure of safety and tolerability | Screening, pre-dose, at select dosing days and at 5 to 7 days post dose for single dose,and 15 to 17 days post first dose in multiple dosing. | Change in ECG parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals | Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing. | Amount excreted in urine at each collection interval (Ae1-t2) all parts. Cumulative amount excreted to 12h and 24h (Ae0-t) depending on Part. Cumulative urine excreted of unchanged drug to 24h (Fe%) and to 12h depending on Part. Volume of urine collected during each collection interval (Vur), and renal clearance (CLr) all parts |
| Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax) | Pre-dose, multiple time points to 24h, at select dosing days, and 5 to 7 days post dosefor single dose,and 15 to 17 days post first dose in multiple dosing. | Peak plasma concentration (Cmax), time at occurrence of Cmax (tmax), Area under the plasma concentration versus time curve (AUC) 0-t, 0- infinity, percent of AUC 0-infinity, Cmax normalized by dose, AUC 0-t normalized for dose. |
| Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP) | Screening, Day-1, Day 4, Day 9 multiple dosing regimen only | qEEg and ERP (P50 sensory gating, Mismatch Negativity and P300) |
| Pharmacodynamic response as measured by Bond and Lader visual analogue scale | Day 1 at multiple timepoints to 24h post dose. | Changes in 3 factor scores (Alertness, Contentedness and Calmness) which will be derived from the individual VAS scores |
| Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF) | Part 1 - 1h, 2h,3h post dose | Maximum observed CSF concentration (Cmax CSF), area under the CSF concentration versus time |
| Pharmacokinetic measures to assess the food effect as measured by ANOVA | Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose. | Food effect analysis will be based on analysis of variance (ANOVA) for treatment differences. |
| Pharmacodynamic response as measured by pupillometry | Multiple time points Day1 to 6h post dose Part 1 only. | Changes in average pupil diameter as measured in 3 different conditions of lux. |
Countries
United Kingdom
Outcome results
None listed