Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects (HTL0018318)

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

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

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Safety Issues
• Intervention / Treatment: Drug: HTL0018318; Drug: Placebo oral capsule

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London Bridge
    • London, London Bridge, United Kingdom, SE1 1YR
      • Richmond Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Heptares Therapeutics Limited
• Investigators: Principal Investigator: Jorg Taubel, MD FFPM, Richmond Pharmacology

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): August 20, 2017
• Study Completion (Actual): August 20, 2017

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 23, 2017
• First Posted (Actual): June 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 7, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: HTL0018318-105; 2017-001245-27 (EudraCT Number); C17011 (Other Identifier: Richmond Pharmacology)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No