Pharmacokinetics Study in Patients With Impaired Hepatic Function

Phase 1

Completed

• Conditions: Patients With Impaired Hepatic Function
• Interventions: Drug: ASP015K

• Registration Number: NCT02586194
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

The objective of this study is to compare and evaluate the pharmacokinetics of ASP015K in patients with impaired hepatic function and subjects with normal hepatic function.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-10-23
• Study First Submitted QC: 2015-10-23
• Study First Posted: 2015-10-26
• Study Start: 2015-12-28
• Primary Completion: 2016-09-27
• Study Completion: 2016-09-27
• Status Verified: 2019-04
• Last Update Submitted: 2024-10-15
• Last Update Posted: 2024-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

A subject is eligible for the study if all of the following apply:

All subjects:

• Body weight: ≥40.0 kg and <90.0 kg

• Body mass index (BMI): ≥17.0 and <30.0 kg/m2

• Female subject must either:

  • Be post-menopausal or surgically sterile.
  • Agree not to try to become pregnant starting at the time of informed consent throughout the study period and for 60 days after the final study drug administration if she is of childbearing potential.

• Agrees to use highly effective contraception

• Agrees not to donate sperm (for male)/ ova (for female) starting at the time of informed consent, and throughout the study period and for 90/60 days after the final study drug administration.

• Female subject agrees not to breastfeed starting at the time of informed consent, and throughout the study period and for 60 days after the final study drug administration.

• Agrees not to participate in a clinical trial, a post-marketing study, or a clinical study during the period from informed consent to post examination.

A patient with impaired hepatic function:

• Impaired hepatic function Child-Pugh Score Class A (mild, 5-6 points) or Class B (moderate, 7-9 points).

A subject with normal hepatic function:

• Healthy, as judged by the investigator/subinvestigator based on physical examinations and all tests obtained at screening and during the period from hospital admission to immediately before study drug administration.

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Exclusion Criteria

A subject will be excluded from participation in this study if any of the following apply:

All subjects:

• Received or is scheduled to receive any investigational drugs in other clinical trials, post-marketing studies or clinical research within 120 days before screening or during the period from screening to the hospital admission.

• Excessive alcohol or smoking habit.

• Applies to any of following concerns of tuberculosis:

  • A history of active tuberculosis
  • Abnormalities detected on a chest X-ray test (at screening)
  • Contact with infectious tuberculous patients

• Applies to any of following concerns except for tuberculosis:

  • Concurrent or previous severe herpes zoster or herpes zoster disseminated
  • More than 1 recurrence of localized herpes zoster
  • Inpatient hospital care for severe infectious disease within 90 days before the hospital admission
  • Treatment with intravenous antibiotics within 90 days before the hospital admission (prophylactic antibiotics are not applicable)
  • Other than above, a people who has a risk of developing infectious diseases (e.g. urethral catheterisation) in judgment of the investigator/subinvestigator

• Vaccination of live vaccines or live attenuated vaccines within 56 days before the hospital admission (inactivated vaccines such as influenza vaccine and pneumococcal vaccine are not applicable).

• Concurrent or previous drug allergies.

• A history of clinically serious allergies (serious allergies: Generalised urticaria which requires hospital admission, allergy which causes anaphylactic shock, etc.).

• Concurrent or previous cardiac failure NYHA class 3 or 4, long QT syndrome and congenital short QT syndrome.

• Development of (an) upper gastrointestinal symptom(s) within 7 days before the hospital admission.

• Concurrent or previous lymphatic disease.

• A history of digestive tract excision, except for a history of appendectomy.

• Previous use of ASP015K.

A patient with impaired hepatic function:

• Unable to start washout of concomitant prohibited medications from at least 14 days prior to the study drug administration.
• Concurrent uncontrolled hypertension.
• Clinically significant abnormality detected on standard 12-lead electrocardiogram at screening or hospital admission.
• eGFR by the GFR estimating equation for Japanese <45 mL/min/1.73 m2 (the first decimal place rounded off) at screening.
• Uncontrolled ascites or pleural effusion observed at screening.
• Concurrent hepatic encephalopathy Coma Scale II or more at screening.
• Underwent hepatic transplantation, or underwent hepatectomy within 1 year before screening.
• Concurrent or previous drug-induced hepatic disorder.
• Concurrent acute hepatic disease.
• With surgically-placed portosystemic shunts including transjugular intrahepatic portosystemic shunts.
• Concurrent biliary obstruction.
• A history of oesophageal haemorrhage or gastric varices haemorrhage within 180 days before screening.
• Irregular or acute, and clinically significant LFT values or changes in clinical symptoms from 30 days before screening to immediately before study drug administration.
• Platelet count <4 × 104/μL, or haemoglobin <9 g/dL at screening.
• Alcohol dependence or unable to remain abstinent during the specified period.
• Concurrent esophagus or gastric varices which have a high risk of clinically significant haemorrhage.
• Concurrent cerebrovascular disorder, serious heart disease, malignant tumour or a history within 5 years before screening, gastrointestinal disease, urinary disease, renal disease, endocrine disease, and respiratory disease.

A subject with normal hepatic function:

• Received or is scheduled to receive medications (including over-the-counter drugs) within 7 days before the hospital admission.
• Deviates from any of the normal range of blood pressure, pulse rate, body temperature and standard 12-lead electrocardiogram at screening or the hospital admission.
• Meets any of the criteria for laboratory tests at screening or the hospital admission.
• eGFR by the GFR estimating equation for Japanese <60 mL/min/1.73 m2 (the first decimal place rounded off) at screening.
• Concurrent or previous hepatic disease, cerebrovascular disorder, malignant tumor, heart disease, gastrointestinal disease, except for a history of appendicitis, renal disease, endocrine disease, respiratory disease, urological disease.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control (Subjects with normal hepatic function)	ASP015K	Oral
Mild hepatic impairment	ASP015K	Oral
Moderate hepatic impairment	ASP015K	Oral

Primary Outcome Measures

Name	Time	Method
PK parameter of ASP015K: Cmax	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	Cmax: Maximum concentration
Pharmacokinetics (PK) parameter of ASP015K: AUCinf	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72 hr after dosing	AUCinf: Area under the concentration-time curve from the time of dosing extrapolated to time infinity
Safety assessed by 12-lead ECGs	Up to 7 days after the study drug dosing
PK parameter of metabolites: AUCinf	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing
PK parameter of metabolites: Cmax	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing
Safety assessed by AEs	Up to 7 days after the study drug dosing
Safety assessed by Vital signs	Up to 7 days after the study drug dosing	Supine blood pressure, supine pulse rate and axillary body temperature
Safety assessed by Laboratory tests	Up to 7 days after the study drug dosing	Hematology, blood biochemistry, and urinalysis

Secondary Outcome Measures

Name	Time	Method
PK parameters of ASP015K: AUClast	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	AUClast: Area under the concentration-time curve from the time of dosing extrapolated to the last measurable concentration
PK parameters of metabolites: t1/2	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing
PK parameters of ASP015K: t1/2	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	t1/2: Terminal elimination half-life
PK parameters of metabolites: AUClast	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing
PK parameters of ASP015K: CL/F	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	CL/F: Apparent total systemic clearance
PK parameters of ASP015K: tmax	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	tmax: Time of Cmax
PK parameters of ASP015K: Vz/F	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing	Vz/F: Apparent volume of distribution during the terminal elimination phase
PK parameters of metabolites: tmax	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60 and 72hr after dosing

Trial Locations

Locations (6)

Site JP00004; 🇯🇵 Tokyo, Japan

Site JP00003; 🇯🇵 Kanagawa, Japan

Site JP00001; 🇯🇵 Fukuoka, Japan

Site JP00002; 🇯🇵 Tokyo, Japan

Site JP00005; 🇯🇵 Tokyo, Japan

Site JP00006; 🇯🇵 Tokyo, Japan