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

• ClinicalTrials.gov Identifier: NCT03198624
• Recruitment Status: Completed
• First Posted: June 26, 2017
• Last Update Posted: September 7, 2017
• Sponsor: Heptares Therapeutics Limited
• Information provided by (Responsible Party): Heptares Therapeutics Limited

Tracking Information

• First Submitted Date: June 19, 2017
• First Posted Date: June 26, 2017
• Last Update Posted Date: September 7, 2017
• Actual Study Start Date: May 16, 2017
• Actual Primary Completion Date: August 20, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2017)

• Cmax [ Time Frame: Baseline to 72 hours ]
  Comparison of pharmacokinetics in plasma
• Tmax [ Time Frame: Baseline to 72 hours ]
  Comparison of pharmacokinetics in plasma
• Area under the curve [ Time Frame: Baseline to 72 hours ]
  Comparison of pharmacokinetics in plasma

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2017)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Part A open label, Part B double blind.

Primary Purpose: Treatment

Condition

• Safety Issues
• Pharmacokinetics

Intervention

• Drug: HTL0018318
  Part A single dose Part B five doses
• Drug: Placebo oral capsule
  Part B only
  Other Name: placebo, placebo - cap

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 23, 2017): 54
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 20, 2017
• Actual Primary Completion Date: August 20, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 20 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03198624
• Other Study ID Numbers: HTL0018318-105; 2017-001245-27 ( EudraCT Number ); C17011 ( Other Identifier: Richmond Pharmacology )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Heptares Therapeutics Limited
• Study Sponsor: Heptares Therapeutics Limited
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jorg Taubel, MD FFPM; Richmond Pharmacology

• PRS Account: Heptares Therapeutics Limited
• Verification Date: September 2017