Measurement of HTL0016878 in Cerebrospinal Fluid

Study Overview
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Brief Summary
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A Phase 1, open-label, randomised, single oral dose study to determine the concentration of HTL0016878 in CSF and plasma in healthy male subjects following dosing with HTL0016878 10 mg or 20 mg oral solution

Detailed Description
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Up to 24 healthy subjects will be enrolled into 4 groups, with 6 subjects per group. Each subject will be randomised to receive a single oral dose of 10 mg or 20 mg HTL0016878 solution and will have a single CSF sample taken via lumbar puncture at either 2 or 6 hours post-dose. Pharmacokinetic blood sampling and safety measures will continue until 24 hours post-dose.

Official Title
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A Phase 1, Open-label, Randomised, Single-centre, Single Oral Dose Study to Determine the Concentration of HTL0016878 in Cerebrospinal Fluid and Plasma in Healthy Male Subjects Following Dosing With HTL0016878 Oral Solution

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: HTL0016878


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a body mass index (BMI) of 18 to 32 kg/m2, inclusive. Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examination, concomitant medication, vital signs, 12-lead ECG, C-SSRS responses, and clinical laboratory evaluations. Willingness to comply with requirements or the trial, including contraception requirements. Able to give fully informed consent. Exclusion Criteria: Positive tests for hepatitis B & C, HIV. Clinically relevant history of abnormal physical or mental health. Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry or coagulation panel and urinalysis), 12-lead ECG and vital signs, or physical findings. History of severe adverse reactions or allergies, or history of an anaphylactic reaction to prescription or non-prescription medication or food. Drug or alcohol abuse. Smoking. Use of medication that inhibits CYP2D6. Participation in other clinical trials of unlicensed medicines in the previous 3 months. Loss of more than 400 mL blood in the previous 3 months. Vital signs, QTcF interval or laboratory values outside the acceptable range. Predicted poor and intermediate CYP2D6 metabolisers. Clinically relevant abnormal findings at the screening assessment. History of epilepsy or seizures. Clinically relevant abnormal medical history or concurrent medical condition disease associated with cognitive impairment and/or psychosis. History of suicidal thoughts or ideation, or any history of insomnia. Use of tobacco and/or nicotine containing products within 90 days of dosing. Habitual and heavy consumption of caffeinated beverages. Consumption of cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and juices made from these fruits) within 3 days before admission. Objection by General Practitioner

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>10 mg dose, CSF sample 2 hours post-dose | Drug: HTL0016878<br>* Oral solution<br>|
| Experimental: Group 2<br>10 mg dose, CSF sample 6 hours post-dose | Drug: HTL0016878<br>* Oral solution<br>|
| Experimental: Group 3<br>20 mg dose, CSF sample 2 hours post-dose | Drug: HTL0016878<br>* Oral solution<br>|
| Experimental: Group 4<br>20 mg dose, CSF sample 6 hours post-dose | Drug: HTL0016878<br>* Oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of HTL0016878 in CSF | Pharmacokinetics | 2 hours | 
| Concentration of HTL0016878 in CSF | Pharmacokinetics | 6 hours | 
| Concentration of HTL0016878 in plasma Cmax | Pharmacokinetics | 0-24 hours | 
| Concentration of HTL0016878 in plasma AUC | Pharmacokinetics | 0-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse events | Safety and Tolerability | Baseline up to 10 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebrospinal Fluid