A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies

Study Overview
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Brief Summary
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To establish the safety and efficacy of HTL0018318 compared with placebo when administered once daily for 12 weeks to patients with dementia with Lewy bodies.

Detailed Description
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To assess the safety, tolerability and efficacy of HTL0018318 at 3 dose levels (once daily) compared with placebo over a 12-week treatment period in patients with dementia with Lewy bodies (DLB). Approximately 140 DLB patients who have not received donepezil (Aricept®) and/or other acetyl cholinesterase inhibitors (AchEi) and approximately 32 DLB patients who have had prior treatment experience with donepezil but have stopped usage will be enrolled.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Dose Ranging Study to Assess the Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies

Conditions
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Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: HTL0018318
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with probable DLB according to the fourth revision of consensus diagnostic criteria for DLB. Clinical imaging evidence from either SPECT or MIBG cardiac scintigraphy that is consistent with a clinical diagnosis of DLB. Partner or caregiver able to support the patient for the duration of the clinical trial. Exclusion Criteria: Patients with a diagnosis of Parkinson disease at least 1 year prior to onset of dementia. Patients with the presence of severe extrapyramidal symptoms Patients with the presence of an illness/condition apart from DLB that could contribute to cognitive dysfunction Patients with poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy, who are currently on more than 2 different antihypertensive treatments Patients with prominent, recurrent episodes of syncope are related to orthostatic hypotension Patients with pulmonary disease or evidence of clinically significant moderate or severe pulmonary symptoms Patients who are taking a range of prohibited and restricted medication Patients who have been prescribed individualised cognitive rehabilitation, stimulation or training that was performed under medical supervision in the 6 months prior to the screening visit Patients who have any known condition(s) that may be contraindicated or interfere with the completion of the nuclear imaging scans.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HTL0018318 high dose<br>oral capsule, once daily | Drug: HTL0018318<br>* Oral capsule<br>|
| Experimental: HTL0018318 mid dose<br>oral capsule, once daily | Drug: HTL0018318<br>* Oral capsule<br>|
| Experimental: HTL0018318 low dose<br>oral capsule, once daily | Drug: HTL0018318<br>* Oral capsule<br>|
| Placebo Comparator: Placebo<br>oral capsule, once daily | Drug: Placebo<br>* Oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment related adverse events | Comparison of HTL0018318 treatment with placebo | Baseline to 12 weeks | 
| Change in systolic, diastolic blood pressure and heart rate | Comparison of HTL0018318 treatment with placebo | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in measures of cognitive impairment | Comparison of HTL0018318 treatment with placebo | Baseline to 12 weeks | 
| Change from baseline in measures of psychosis (i.e. hallucinations and delusions) | Comparison of HTL0018318 treatment with placebo | Baseline to 12 weeks |