Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects

Study Overview
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Brief Summary
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This is a single and multiple dose, parallel group study to assess safety and pharmacokinetics of oral HTL0018318 in healthy Japanese and Caucasian subjects.

Detailed Description
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This is a single and multiple dose, parallel group study to assess safety and pharmacokinetics of oral HTL0018318 in healthy Japanese and Caucasian subjects. The study will be conducted in two parts: (A) single doses of HTL0018318 in healthy, adult, male Caucasian and Japanese subjects; (B) multiple doses of HTL0018318 in healthy, adult, male Caucasian and Japanese subjects.

Official Title
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A Two-part, Single and Multiple Dose, Parallel Group Study to Assess Safety and Pharmacokinetics of Oral HTL0018318 in Healthy Japanese and Caucasian Subjects

Conditions
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Safety Issues, Pharmacokinetics

Intervention / Treatment
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* Drug: HTL0018318
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects, either Caucasian or Japanese aged ≥20 and ≤40 years. Japanese subjects must have lived outside of Japan for ≤ 5 years in total and be first generation Japanese, defined as born in Japan and having 4 biologic grandparents who are ethnic Japanese. The Caucasian subjects should be distinguished especially by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa and western Asia. Therefore, the study may include Caucasian subjects from North America, New Zealand, Australia and South Africa. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive. Male subjects, if heterosexually active and with a female partner of childbearing potential or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) for the treatment period and for at least 3 months after the end of the systemic exposure of the study drug. Satisfactory medical assessment with no clinically significant or relevant abnormalities. Able to perform spirometry/peak flow with a satisfactory technique at screening. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the International Council of Harmonization Good Clinical Practice (GCP) Guideline E6. An understanding, ability, and willingness to fully comply with study procedures and restrictions Exclusion Criteria: Any history of any condition associated with cognitive impairment, including but not limited to schizophrenia and dementia. History of epilepsy or seizures of any kind at any time. Current or relevant history of any physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures. The history or presence of any of the following cardiac conditions: known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise related clinically significant cardiac events. Presence or history of drug or alcohol abuse in the last 5 years, or the inability to refrain from alcohol use from 48 hours before screening, dosing and each scheduled visit until the end of the study. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch, electronic cigarettes) within 3 months prior to the planned first day of dosing. Use of prescription medications within 14 days or 10 half-lives (whichever is longer) prior to Day 1 of the dosing period, or any over-the-counter (OTC) medication (including multivitamin, herbal, or homeopathic preparations, excluding hormonal contraception, hormone-replacement therapy, and/or an occasional dose of acetaminophen) within 7 days prior to Day 1 of the dosing period. History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc). Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first day of dosing.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HTL0018318 Low dose, Part A.<br>Part A. 1 single dose on day 1. Discharged on day 4 of Period 1 (following 10 day washout). | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>|
| Active Comparator: HTL0018318 High dose, Part A<br>1 single dose on day 1. Discharged on day 4 of period 2 (following 10 day washout). | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>|
| Active Comparator: HTL0018318 Low dose, Part B<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1. | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>|
| Placebo Comparator: Placebo oral capsule, Part B<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1. | Drug: Placebo oral capsule<br>* Part B only<br>* Other names: placebo, placebo - cap;|
| Active Comparator: HTL0018318 High dose, Part B.<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2. | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>|
| Placebo Comparator: Placebo oral capsule, Part B.<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2. | Drug: Placebo oral capsule<br>* Part B only<br>* Other names: placebo, placebo - cap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | 
| Tmax | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | 
| Area under the curve | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay in absorption (Tlag) | Pharmacokinetics in plasma | Baseline to 72 hours | 
| Rate of elimination | Pharmacokinetics in plasma | Baseline to 72 hours | 
| Half life (t1/2) | Pharmacokinetics in plasma | Baseline to 72 hours | 
| Amount excreted in urine | Pharmacokinetics in urine | Baseline to 72 hours | 
| Fraction of dose eliminated unchanged in urine (fe/F) | Pharmacokinetics in urine | Baseline to 72 hours | 
| Treatment emergent adverse events (TEAEs) | Safety and tolerability | Up to 14 day post dose | 
| Number of participants with abnormal physical exam results | Safety and tolerability | Up to 14 day post dose | 
| Heart Rate | Safety and tolerability | Up to 14 day post dose | 
| Number of participants with abnormal laboratory values | Safety and tolerability | Up to 14 day post dose | 
| ECG | Safety and tolerability | Up to 14 day post dose | 
| Blood pressure | Safety and tolerability | Up to 14 day post dose |