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

Completed · Phase 1

Conditions studied: Hepatic Impairment

In brief

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.

Key facts

Study ID

NCT04166942

Run by

Kadmon, a Sanofi Company

People needed

35

Starts

2019-12-11

Expected to finish

2022-06-06

Last updated by the study team

2022-07-18

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: accepted.

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.
• 'Stable' is defined as no clinically significant change in disease status within the last 3 months (90 days), as documented by the subject's recent medical history (eg, no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time by more than 50%).
• Subjects with mild, moderate, or severe hepatic impairment may have medical findings consistent with their hepatic dysfunction as determined by 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).
• Non-hepatic, abnormal clinical laboratory evaluations not clinically relevant, as judged by the Investigator (or designee) and Covance Medical Monitor.
• Currently on a stable medication regimen, defined as not starting new drug(s) or changing drug dose(s) within 30 days of administration of study drug (Day 1). Concomitant medications administered within 30 days prior to administration of KD025 (Day 1) must be approved by the Investigator (or designee), Sponsor, and Covance Medical Monitor.
• Anemia secondary to hepatic disease will be acceptable, if hemoglobin >9 g/dL and anemia symptoms are not clinically significant as judged by the Investigator (or designee) and Covance Medical Monitor.
• Platelet count ≥35 × 10\^9 platelets/L.
• Subjects with diabetes mellitus may be included, provided the subjects have:
• Glycosylated hemoglobin A1c values ≤9.5% at Screening. Subjects with values outside this range may be allowed by the Covance Medical Monitor on a case-by-case basis.
• Blood glucose values ≤240 mg/dL at Screening and Check-in (Day -1) while on subjects' normal diabetes medication.

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).
• Receipt of blood products within 2 months prior to Check-in.
• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• Poor peripheral venous access.
• Have previously completed or withdrawn from this study or any other study investigating KD025, and have previously received KD025.
• Subjects who, in the opinion of the Investigator (or designee) should not participate in this study.
• For Subjects with Normal Hepatic Function Only:
• QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms confirmed by repeat measurement.
• Evidence of hepatorenal syndrome and/or estimated creatinine clearance range <90 mL/min, as determined by the Investigator (or designee), calculated using the Cockcroft-Gault equation at Screening and Check-in (Day -1).
• For male subjects: ([1.23 × {140-age} × {weight in kg})])/(serum creatinine in μmol/L) For female subjects: ([1.04 × {140-age} × {weight in kg})])/(serum creatinine in μmol/L)
• Ventricular dysfunction or history of risk factors for Torsade de Pointes (e.g., unexplained syncope, known long QT syndrome, heart failure, and cardiomyopathy). Subjects will be excluded if there is a family history of long QT syndrome.

Where it is running

• Inland Empire Clinical Trials, LLC-HQ — Rialto, California, United States
• Clinical Pharmacology of Miami — Miami, Florida, United States
• Advanced Pharma CR, LLC — Miami, Florida, United States
• Omega Research Group — Orlando, Florida, United States
• The Liver Institute — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.