Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects

Phase 1

Completed

• Conditions: Safety Issues; Pharmacokinetics
• Interventions: Drug: Placebo oral capsule; Drug: HTL0018318

• Registration Number: NCT03198624
• Lead Sponsor: Heptares Therapeutics Limited

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-05-16
• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-23
• Study First Posted: 2017-06-26
• Primary Completion: 2017-08-20
• Study Completion: 2017-08-20
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-06
• Last Update Posted: 2017-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 54

Inclusion Criteria

1. Male subjects, either Caucasian or Japanese aged ≥20 and ≤40 years.
2. 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.
3. 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.
4. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive.
5. 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.
6. Satisfactory medical assessment with no clinically significant or relevant abnormalities.
7. Able to perform spirometry/peak flow with a satisfactory technique at screening.
8. 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.
9. An understanding, ability, and willingness to fully comply with study procedures and restrictions

Exclusion Criteria

1. Any history of any condition associated with cognitive impairment, including but not limited to schizophrenia and dementia.
2. History of epilepsy or seizures of any kind at any time.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc).
9. Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first day of dosing.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo oral capsule, Part B	Placebo oral capsule	1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1.
Placebo oral capsule, Part B.	Placebo oral capsule	1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2.
HTL0018318 Low dose, Part A.	HTL0018318	Part A. 1 single dose on day 1. Discharged on day 4 of Period 1 (following 10 day washout).
HTL0018318 High dose, Part A	HTL0018318	1 single dose on day 1. Discharged on day 4 of period 2 (following 10 day washout).
HTL0018318 High dose, Part B.	HTL0018318	1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2.
HTL0018318 Low dose, Part B	HTL0018318	1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1.

Primary Outcome Measures

Name	Time	Method
Cmax	Baseline to 72 hours	Comparison of pharmacokinetics in plasma
Tmax	Baseline to 72 hours	Comparison of pharmacokinetics in plasma
Area under the curve	Baseline to 72 hours	Comparison of pharmacokinetics in plasma

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Richmond Pharmacology; 🇬🇧 London, London Bridge, United Kingdom