KD025 Hepatic Impairment Study With Normal Hepatic Function and Subjects With Varying Degrees of Hepatic Impairment

NCT04166942 | Completed Phase 1 FDA Drug

• 2 other identifiers: POP17629KD025-109
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

Brief Summary

This is a study to characterize the pharmacokinetics, safety and tolerability of KD025 and KD025 metabolites in subjects with mild, moderate or severe hepatic impairment compared to healthy subjects with normal hepatic function.

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (8)

• PK: AUC(0-inf)

  Area under the concentration-time curve from time 0 to infinity

  Day 1 through Day 3

• PK: AUC(0-t)

  Area under the concentration-time curve from time 0 to the last measurable concentration

  Day 1 through Day 3

• PK: C(max)

  Maximum observed concentration

  Day 1 through Day 3

• PK: t(max)

  Time of the observed maximum concentration

  Day 1 through Day 3

• PK: t(1/2)

  Terminal elimination half-life

  Day 1 through Day 3

• PK: t(last)

  Time of the last measurable concentration

  Day 1 through Day 3

• PK: CL/F

  Apparent total clearance

  Day 1 through Day 3

• PK: Vz/F

  Apparent volume of distribution

  Day 1 through Day 3

Secondary Outcomes (1)

• Safety: Incidence and Severity of Adverse Events (AEs)

  Screening through Follow-up on Day 10

Study Arms (4)

Normal Hepatic Function (Group 1--Control)

EXPERIMENTAL

Matched healthy subjects with normal hepatic function

Drug: KD025

Mild Hepatic Impairment (Group 2)

EXPERIMENTAL

Subjects with mild hepatic impairment based on Child-Pugh Class A score of 5 or 6

Drug: KD025

Moderate Hepatic Impairment (Group 3)

EXPERIMENTAL

Subjects with moderate hepatic impairment based on Child-Pugh Class B score of 7 to 9

Drug: KD025

Severe Hepatic Impairment (Group 4)

EXPERIMENTAL

Subjects with severe hepatic impairment based on Child-Pugh Class C score of 10 to 14

Drug: KD025

Interventions

KD025 DRUG

Single dose of 200 mg KD025 orally

Also known as: belumosudil

Mild Hepatic Impairment (Group 2); Moderate Hepatic Impairment (Group 3); Normal Hepatic Function (Group 1--Control); Severe Hepatic Impairment (Group 4)

Eligibility Criteria

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

You may qualify if:

• For All Subjects:
• Subjects must satisfy all of the following criteria at the Screening visit, unless otherwise stated:
• Males or females, of any race, between 18 and 75 years of age, inclusive.
• Body mass index between 18.0 and 38.0 kg/m\^2, inclusive.
• Females of non-childbearing potential defined as permanently sterile (ie, due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as females at least 45 years of age with at least 12 months post-cessation of menses without an alternative medical cause, even with a follicle-stimulating hormone level ≤40 mIU/mL, unless on hormone replacement therapy).
• Males will agree to use contraception
• Male subjects must not donate sperm from Check-in (Day -1) until 90 days after the Follow-up visit.
• Able to comprehend and willing to sign an informed consent form and to abide by the study restrictions.
• For Subjects with Normal Hepatic Function Only:
• In good health, determined by no clinically significant findings from medical history, PE, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations at Screening and Check-in (Day -1), as assessed by the Investigator (or designee).
• Matched to subjects with mild, moderate, or severe hepatic impairment in sex, age (±10 years), and body mass index (±20%).
• For Subjects with Hepatic Impairment Only:
• Documented chronic stable liver disease (Child-Pugh Class A \[mild\], B \[moderate\], or C \[severe\] at Screening); diagnosis of hepatic impairment due to parenchymal liver disease. If the Child-Pugh Class of a subject differs between Screening and Check-in, the Child-Pugh Class documented at Screening will be utilized for enrollment. This will exclude biliary liver cirrhosis or other causes of hepatic impairment unrelated to parenchymal disorder.:
• 'Documented' is defined by at least 1 of the following: medical history, PE, hepatic ultrasound, computed axial tomography scan, magnetic resonance imaging, and/or liver biopsy.
• 'Chronic' is defined as \>6 months.

You may not qualify if:

• Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit, unless otherwise stated:
• For All Subjects:
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
• Clinically significant physical examination abnormality, as determined by the Investigator (or designee).
• Use or intend to use any drugs known to be moderate or strong inhibitors or inducers of CYP3A4 within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee) in consultation with the Covance Medical Monitor.
• Use or intend to use any proton pump inhibitors or H2 antagonists within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee) in consultation with the Covance Medical Monitor.
• Use or intend to use any phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
• History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
• Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
• Positive urine drug screen at Screening and/or Check-in (Day -1) that is not otherwise explained by permitted concomitant medication, or positive alcohol test result at Check-in (Day -1). Either a breath or urine alcohol test may be performed in accordance with the standard practice of each CRU.
• Positive human immunodeficiency virus test.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives (whichever is longer) of the investigational drug, prior to dosing.
• Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to Check-in (Day -1).

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (5)

Inland Empire Clinical Trials, LLC-HQ

Rialto, California, 92377, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014-3616, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

Omega Research Group

Orlando, Florida, 32810, United States

Location

The Liver Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

KD025; belumosudil

Study Design

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

Model Details: Open-label, non-randomized, parallel-group study with the following subject treatment arms: Group 1: normal hepatic function; Group 2: mild hepatic impairment; Group 3: moderate hepatic impairment; Group 4: severe hepatic impairment

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 18, 2019
• Study Start: December 11, 2019
• Primary Completion: June 6, 2022
• Study Completion: June 6, 2022
• Last Updated: July 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)