Relative Bioavailability Study in Healthy Subjects to Evaluate the Pharmacokinetics of HTL0009936 After One Dose of Prototype Formulation

Study Overview
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Brief Summary
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The purpose of this study is to find a modified release oral tablet formulation for this drug, which will be safe and well tolerated.

Detailed Description
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The aim of the study is to develop a modified release oral tablet formulation that maintains plasma concentrations within the target therapeutic range, and is safe and tolerable.

Official Title
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A Phase 1 Relative Bioavailability Study in Healthy CYP2D6 Intermediate (IM) and Extensive Metaboliser (EM) Subjects, Designed to Evaluate the Pharmacokinetic (PK) Profile of HTL0009936 Following Single Dose Administration of Modified Release (MR) Prototype Formulations

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: HTL0009936 modified release
* Drug: HTL0009936 immediate release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males & females Aged 18 to 65 years Body mass index of 18.0 to 35.0 kg/m2 CYP2D6 (intermediate or extensive metabolizer) Exclusion Criteria: Subjects with a resting heart rate (HR) >90 bpm, and/or systolic blood pressure (BP) >150 mmHg, and/or diastolic BP >90 mmHg Subjects with QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms (males) or >470 ms (females) Personal or family history of long QT syndrome or sudden death Subjects who are CYP2D6 (poor or ultra-rapid metabolizer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HTL0009936 modified release (MR) Formulation<br>Intervention: 5 different modified release formulations of HTL0009936, as a single dose | Drug: HTL0009936 modified release<br>* HTL0009936 modified release<br>|
| Active Comparator: HTL00009936 immediate release (IR) fasted<br>Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state | Drug: HTL0009936 immediate release<br>* HTL0009936 immediate release<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tlag | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which HTL0009936 was first quantifiable in a concentration vs time profile (Tlag). | 14 weeks | 
| Frel | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of relative bioavailability (Frel) of HTL0009936 MR prototype formulations compared to the IR reference formulation and, if applicable, MR prototype formulations in the fed state compared to fasted state. | 14 weeks | 
| Tmax | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which the maximum observed HTL0009936 concentration (Cmax) was apparent (Tmax) | 14 weeks | 
| Cmax | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax. | 14 weeks | 
| Concentration of HTL0009936 at 6 hours post dose (C6) | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 6 hours post-dose (C6) | 6 hours post dose | 
| AUC (0-last) | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to the last measurable concentration (AUC(0-last)) | 14 weeks | 
| AUC (0-inf) | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to extrapolated to infinity (AUC(0-inf)). | 14 weeks | 
| AUC%extrap | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of percentage of AUC(0-inf) extrapolated beyond last measured time point (AUC%extrap). | 14 weeks | 
| Lambda-z | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the slope of the apparent elimination phase (Lambda-z). | 14 weeks | 
| T1/2 | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the apparent elimination half-life (T1/2). | 14 weeks | 
| Dose normalized AUC | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized AUC (AUC/D) will be calculated. | 14 weeks | 
| Dose normalized Cmax | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized Cmax (Cmax/D) will be calculated. | 14 weeks | 
| Concentration of HTL0009936 at 12 hours post dose (C12) | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 12 hours post-dose (C12) | 12 hours post dose | 
| Concentration of HTL0009936 at 24 hours post dose (C24) | The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 24 hours post-dose (C24) | 24 hours post dose |