Comparison of Blood Levels of HTL0016878 From an Oral Capsule and an Oral Solution

Study Overview
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Brief Summary
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This is a randomised, open-label, 3-period, crossover single dose study to assess the relative bioavailability of two formulations of HTL0016878: an oral solution of HCl salt form (the reference product) and an oral capsule containing citrate salt (the test product); and of the effect of food on the pharmacokinetics of the capsule formulation.

Detailed Description
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Fifteen healthy male or female subjects will be enrolled. Each subject will have 3 study sessions and receive a single oral dose of 10 mg HTL0016878 on Day 1 of each study session. Subjects will receive the HTL0016878.HCl oral solution in the fasted state in 1 session, and the HTL0016878.citrate capsule, in the fasted state and after a high-fat meal, respectively, in the other 2 sessions. Each subject will be randomised to 1 of 3 treatment sequences (5 subjects to each sequence). There will be a washout of at least 10 days between doses. Subjects will be screened within 35 days before their first dose of HTL0016878. In each study session, subjects will be resident on the ward from the day before dosing (Day -1) until completion of procedures 72 h after their dose (Day 4). Subjects will return for a follow up visit 10-13 days after their final dose of trial medication.

Official Title
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Phase 1, Randomised, Open-label, 3-period Crossover, Single Dose Study in Healthy Subjects, to Assess Relative Bioavailability From an Oral Capsule of HTL0016878 Citrate Salt Versus an Oral Solution of HTL0016878 Hydrochloride Salt

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: HTL0016878.HCl Solution 10 mg
* Drug: HTL0016878.Citrate Capsule 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or females, aged 18-50 years Female subjects must agree to use highly effective contraception Weigh 60 kg or more, with a BMI in the range 18.0-30.0 kg/m2 Sufficient intelligence to understand the nature of the trial Willingness to give written consent to participate Agree to use the contraception requirements of the trial Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication Willingness to give written consent to have data entered into The Overvolunteering Prevention System Exclusion Criteria: Woman who is pregnant or lactating Clinically relevant abnormal history, physical findings, ECG, or laboratory values Presence or history of acute or chronic illness, or mental health problem Impaired neurological, endocrine, thyroid, cardiovascular, respiratory, gastrointestinal, hepatic or renal function, diabetes mellitus, coronary heart disease, or history of any psychiatric disorder or psychotic mental illness Cancer during the 5 years before screening Supine blood pressure and heart rate outside the ranges: 90-140 mm Hg systolic and 50-90 mm Hg diastolic blood pressure; heart rate 45-80 beats/min Supine QT interval (QTcF) outside the ranges 300-450 msec (men) and 300-470 msec (women) Personal or family history of long QT syndrome or family sudden death Positive test for hepatitis B, hepatitis C or HIV Aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase or total bilirubin levels > 1.5 times the upper limit of normal Creatinine clearance < 80 mL/min/1.73 m2 Presence or history of drug or alcohol abuse in the past 5 years; or regular intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women); or use of cigarettes, tobacco and/or nicotine-containing products during the 3 months before dosing Evidence of drug abuse or positive alcohol or cotinine test results Positive pregnancy test Habitual and heavy consumption of caffeinated beverages Use of a prescription or over-the-counter medicine, any herbal remedy, or nutritional supplement Receipt of a vaccine against COVID-19 in the 14 days before dosing Received live attenuated vaccination within 6 weeks prior to Screening History of severe allergies Use of any drugs that are inhibitors of CYP2D6 Poor metaboliser of CYP2D6 History of epilepsy or seizures Any disease associated with cognitive impairment and/or psychosis Suicidal thoughts or ideation, or insomnia Any history of mental illness (including anxiety, depression), which required medical intervention Presence or history of severe adverse reaction to any drug Surgery or medical condition that might affect absorption of medicines Receipt of an investigational product as part of another clinical trial within the 3 months before dosing in this study Receipt of HTL0016878 in a previous clinical trial Loss of more than 400 mL blood during the 3 months before dosing Unwilling to eat a high-fat breakfast Possibility that the volunteer will not cooperate with the requirements of the protocol Objection by GP to volunteer entering trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Solution Fasted<br>HTL0016878.HCl 10 mg, single dose, oral solution, fasted | Drug: HTL0016878.HCl Solution 10 mg<br>* Oral solution fasted<br>|
| Experimental: Oral Capsule Fasted<br>HTL0016878.citrate 10 mg, single dose, oral capsule, fasted | Drug: HTL0016878.Citrate Capsule 10 mg<br>* Oral capsule fed or fasted<br>|
| Experimental: Oral Capsule Fed<br>HTL0016878.citrate 10 mg, single dose, oral capsule, fed | Drug: HTL0016878.Citrate Capsule 10 mg<br>* Oral capsule fed or fasted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of HTL0016878 in plasma Cmax | Pharmacokinetics | 0-72 hours | 
| Concentration of HTL0016878 in plasma AUC | Pharmacokinetics | 0-72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | Safety and Tolerability | Baseline up to 13 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative Bioavailability