Phase 1 Study Investigating Effects of HTL0009936 on Cognition and BOLD fMRI Signals in Healthy Elderly Subjects

Study Overview
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Brief Summary
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To determine if treatment with HTL0009936 will lead to changes in neural activity, measured using the fMRI BOLD signal and ASL, in brain areas that are associated with spatial and working memory, learning and executive functioning.

Official Title
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Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Phase 1, Exploratory Study Investigating the Effects of HTL0009936 on Cognition and BOLD fMRI Signals in Healthy Elderly Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: HTL0009936
* Drug: HTL0009936 matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy on the basis of medical history, physical examination, vital signs, 12-lead ECG, haematology, blood chemistry, urinalysis and a pre-study psychological assessment. Mini Mental State Examination (MMSE) Score of ≥24. Intermediate or extensive metaboliser as determined by CYP2D6 genotype. Fluent English speaker. Right-handed. Not a regular smoker Exclusion Criteria: Recreational drug use within 3 months prior to Screening Visit. Positive alcohol breath test. Positive urine drug screen. Consumption of large amounts of caffeinated drinks. Consumption of any food or any drinks containing cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges. Ultra-rapid or poor metabolizer as determined by CYP2D6 genotype. By self-report, taking two or more daytime naps per week which in the opinion of the investigator is likely to interfere with the ability of the subject to complete the study procedures. History of, or presents (in the opinion of the Investigator) with, significant neurological or psychiatric conditions. Personal or family history of congenital long QT syndrome or sudden death. Concomitant use of drugs that are metabolised by and/or are inhibitors of CYP2D6. Concomitant use of drugs that are substrates for the organic cation transporter 2. History of significant claustrophobia. Fulfils any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants).

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HTL0009936 high dose<br>high dose infusion | Drug: HTL0009936<br> <br> |
| Experimental: HTL0009936 low dose<br>low dose infusion | Drug: HTL0009936<br> <br> |
| Placebo Comparator: HTL0009936 matching placebo<br>matching infusion | Drug: HTL0009936 matching placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood oxygen level dependent (BOLD) signal in functional Magnetic Resonance Imaging (fMRI) of the brain areas associated with cognitive tasks |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD signal in fMRI in other brain regions involved in the regulation of cognitive processes during cognitive tasks |  | Day 1 | 
| cerebral blood flow, assessed using Arterial Spin Labelling (ASL) |  | Day 1 | 
| adverse events |  | Day 1 | 
| blood pressure |  | Day 1 | 
| 12-lead electrocardiogram |  | Day 1 |