Single-dose Study to Investigate the Plasma PK of KW-6356 and Its Major Metabolite

NCT04190654 | Completed Phase 1 FDA Drug

• 1 other identifier: 6356-006
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, non-randomized, single-dose study to investigate the plasma PK of KW-6356 and its major metabolite, after a single oral dose of KW-6356, in subjects with mild or moderate hepatic impairment and in healthy adults

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (7)

• Cmax

  Maximum observed concentration (KW-6356 and its major metabolite in plasma).

  Day 1 to Day 12

• AUC0-t

  AUC from time zero to the last quantifiable concentration (KW-6356 and its major metabolite in plasma).

  Day 1 to Day 12

• AUC0-∞

  AUC from time zero to infinity (KW-6356 and its major metabolite in plasma).

  Day 1 to Day 12

• tmax

  Time of the maximum observed concentration (KW-6356 and its major metabolite in plasma).

  Day 1 to Day 12

• t1/2

  Elimination half-life (KW-6356 in plasma).

  Day 1 to Day 12

• CL/F

  Apparent total clearance (KW-6356 in plasma).

  Day 1 to Day 12

• Vz/F

  Volume of distribution during terminal elimination phase (KW-6356 in plasma).

  Day 1 to Day 12

Secondary Outcomes (6)

• Plasma protein binding of KW-6356 and its major metabolite

  1 hour after dosing Day 1, and 24 hours after dosing Day 2

• Adverse Events

  From screening through study completion, an average of 40 days.

• Clinical Laboratory Evaluations

  From screening through study completion, an average of 40 days.

• Vital signs

  From screening through study completion, an average of 40 days.

• 12-lead ECG

  From screening through study completion, an average of 40 days.

Study Arms (3)

Mild Hepatic Impairment

EXPERIMENTAL

Subjects with mild hepatic impairment (Child-Pugh class A score of 5 or 6)

Drug: KW-6356

Moderate Hepatic Impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment (Child-Pugh class B score of 7 to 9)

Drug: KW-6356

Healthy Subjects

EXPERIMENTAL

Healthy adults matched with the subjects in Group A and Group B at 1:1 for age (± 10 years), sex, and BMI (± 20%)

Drug: KW-6356

Interventions

KW-6356 DRUG

Single oral dose of KW-6356

Healthy Subjects; Mild Hepatic Impairment; Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects:
• Individuals who provide freely given written consent for participating in the study.
• Men and women aged ≥ 18 and ≤ 75 years at the date of providing informed consent.
• Subjects with a BMI in the range 18.0 to 40.0 kg/m2.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• Subjects with Hepatic Impairment:
• Subjects must meet the criteria for mild or moderate hepatic impairment based on CP classification. Subjects will be classified at Screening based on CP score and classification will be repeated at Check-in. If the hepatic function classification for the subject is not the same at the 2 timepoints, enrollment of the subject into a hepatic category group will be based on the CP score at Screening.
• Subjects have stable hepatic function with a diagnosis of chronic disease of \> 6 months, defined as no clinically significant change in disease status within the 60 days prior to the Screening visit or 90 days prior to drug administration on Day 1 (whichever is longer), as documented by the subject's recent medical history.
• Subjects are on a stable medication dose(s) and/or treatment regimen(s) for treatment of hepatic impairment during the 30 days preceding the first dose of IMP. Drugs known to be moderate-to-potent inhibitors or inducers of CYP3A4/5 enzyme will not be allowed. Subjects requiring medications that are moderate-to-potent inhibitors or inducers of CYP3A4/5 may have these medications discontinued for purposes of qualifying for at least 30 days prior to dosing day for this study. Adjustments may be made if deemed medically safe and also acceptable to the Sponsor and Medical Monitor.
• Subjects with mild or moderate hepatic impairment may have medical findings consistent with their hepatic dysfunction, as determined by medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations at Screening and Check-in. Subjects with abnormal findings considered not clinically significant by the Investigator will be eligible. Vital signs between the following ranges and stable (measured in a supine position after a minimum of 5 minutes supine):
• Systolic blood pressure ≥ 90 and ≤ 160 mmHg
• Diastolic blood pressure ≥ 50 and ≤ 95 mmHg
• Pulse rate ≥ 45 and ≤ 100 bpm
• Healthy Subjects with Normal Hepatic Function:

You may not qualify if:

• All Subjects:
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or clinically significant psychiatric disorder, as determined by the Investigator. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, hernia repair, and cholecystectomy will be allowed).
• Use of any prescriptions or substances that are known to be moderate to strong inducers or inhibitors of CYP3A4/5 within 30 days prior to dosing and during the study.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator.
• Consumption of foods and beverages containing poppy seeds, grapefruit, or Seville oranges from 7 days prior to dosing until End of Study.
• Consumption of caffeine-containing foods and beverages from 48 hours prior to Check-in.
• Poor peripheral venous access.
• Engaged in strenuous exercise within 7 days of Check-in.
• Alcohol consumption is prohibited from 72 hours prior to dosing and during the study.
• Subjects who were dosed in another clinical trial, or equivalent study of a drug or medical device, within 30 days, or 5 times the half-life of the IMP (whichever is longer) prior to IMP administration in the current study.
• Subjects with receipt of blood products within 2 months prior to Check-in.
• Subjects with donation of blood (\> 200 mL) from 3 months prior to Screening, donation of plasma from 2 weeks prior to Screening, or donation of platelets from 6 weeks prior to Screening.
• Subjects who test positive for acquired human immunodeficiency virus, including positive serology test results for hepatitis B surface antigen and/or human immunodeficiency virus 1/2. Subjects whose results are compatible with prior immunization for hepatitis B or natural immunity, and who tested positive for isolated hepatitis B core antibody with viral load negative may be included at the discretion of the Investigator.
• Subjects who test positive for drugs of abuse at Screening and Check-in, with the exception of prescribed opioids and tetrahydrocannabinols (THC, marijuana) for pain management (Investigator verification required).

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (3)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014-3616, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 9, 2019
• Study Start: November 26, 2019
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)