Clinical trial NCT03198624: Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects
Official title: A Two-part, Single and Multiple Dose, Parallel Group Study to Assess Safety and Pharmacokinetics of Oral HTL0018318 in Healthy Japanese and Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety Issues
Pharmacokinetics
Lead sponsor: Nxera Pharma UK Limited
Sponsor class: INDUSTRY
First posted: 2017-06-26
Enrollment: 54
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: Baseline to 72 hours
measure: Tmax
timeFrame: Baseline to 72 hours
measure: Area under the curve
timeFrame: Baseline to 72 hours
Secondary outcomes:
measure: Delay in absorption (Tlag)
timeFrame: Baseline to 72 hours
measure: Rate of elimination
timeFrame: Baseline to 72 hours
measure: Half life (t1/2)
timeFrame: Baseline to 72 hours
measure: Amount excreted in urine
timeFrame: Baseline to 72 hours
measure: Fraction of dose eliminated unchanged in urine (fe/F)
timeFrame: Baseline to 72 hours
measure: Treatment emergent adverse events (TEAEs)
timeFrame: Up to 14 day post dose
measure: Number of participants with abnormal physical exam results
timeFrame: Up to 14 day post dose
measure: Heart Rate
timeFrame: Up to 14 day post dose
measure: Number of participants with abnormal laboratory values
timeFrame: Up to 14 day post dose
measure: ECG
timeFrame: Up to 14 day post dose
measure: Blood pressure
timeFrame: Up to 14 day post dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology
state: London Bridge
Study officials:
affiliation: Richmond Pharmacology
name: Jorg Taubel, MD FFPM
role: PRINCIPAL_INVESTIGATOR
References: