Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects

NCT03198624 | Completed Phase 1

• 3 other identifiers: HTL0018318-1052017-001245-27C17011
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Safety Issues; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Delay in absorption (Tlag)

  Baseline to 72 hours

• Rate of elimination

  Baseline to 72 hours

• Half life (t1/2)

  Baseline to 72 hours

• Amount excreted in urine

  Baseline to 72 hours

• Fraction of dose eliminated unchanged in urine (fe/F)

  Baseline to 72 hours

Study Arms (6)

HTL0018318 Low dose, Part A.

ACTIVE COMPARATOR

Part A. 1 single dose on day 1. Discharged on day 4 of Period 1 (following 10 day washout).

Drug: HTL0018318

HTL0018318 High dose, Part A

ACTIVE COMPARATOR

1 single dose on day 1. Discharged on day 4 of period 2 (following 10 day washout).

Drug: HTL0018318

HTL0018318 Low dose, Part B

ACTIVE COMPARATOR

1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1.

Drug: HTL0018318

Placebo oral capsule, Part B

PLACEBO COMPARATOR

1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1.

Drug: Placebo oral capsule

HTL0018318 High dose, Part B.

ACTIVE COMPARATOR

1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2.

Drug: HTL0018318

Placebo oral capsule, Part B.

PLACEBO COMPARATOR

1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2.

Drug: Placebo oral capsule

Interventions

HTL0018318 DRUG

Part A single dose Part B five doses

HTL0018318 High dose, Part A; HTL0018318 High dose, Part B.; HTL0018318 Low dose, Part A.; HTL0018318 Low dose, Part B

Placebo oral capsule DRUG

Part B only

Also known as: placebo, placebo - cap

Placebo oral capsule, Part B; Placebo oral capsule, Part B.

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead

Study Sites (1)

Richmond Pharmacology

London, London Bridge, SE1 1YR, United Kingdom

Location

Study Officials

• Jorg Taubel, MD FFPM

  Richmond Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part A open label, Part B double blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 26, 2017
• Study Start: May 16, 2017
• Primary Completion: August 20, 2017
• Study Completion: August 20, 2017
• Last Updated: September 7, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)