Pharmacokinetics Study in Patients With Impaired Renal Function and Subjects With Normal Renal Function

Study Overview
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Brief Summary
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The objective of this study is to compare the pharmacokinetics of ASP015K in patients with impaired renal function and subjects with normal renal function.

Official Title
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Pharmacokinetic (PK) Study of ASP015K -Evaluation of Pharmacokinetics in Patients With Impaired Renal Function and Subjects With Normal Renal Function-

Conditions
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Patients With Impaired Renal Function

Intervention / Treatment
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* Drug: ASP015K


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subject Body weight): ≥40.0 kg and <90.0 kg Body mass index BMI: ≥17.6 and <30.0 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. Female subjects who agree not to breastfeed starting at informed consent and throughout the study period and for 60 days after the final study drug administration Agree not to donate ova for female / sperm for male starting at informed consent and throughout the study period and for 60/90 days after the final study drug administration Agree to use highly effective contraception Patients with impaired renal function Patients with eGFR by GFR predictive equation for Japanese within the following ranges at screening and who is not undergoing dialysis. Patients with mild impaired renal function (eGFR; ≥60 mL/min/1.73 m2 and <90 mL/min/1.73 m2) Patients with moderate impaired renal function (eGFR; ≥30 mL/min/1.73 m2 and <60 mL/min/1.73 m2) Patients with severe impaired renal function (eGFR; ≥15 mL/min/1.73 m2 and <30 mL/min/1.73 m2) Patients whose treatment regimen (including diet) for renal impairment or complications remain unchanged within 14 days prior to hospital admission day (Day -1), or patients who receive treatments (including diet) that need not to be changed during the period from 14 days before hospital admission day (Day -1) to follow-up examination in the opinion of the investigator or sub-investigator. Subjects with normal renal function Subjects with eGFR by GFR predictive equation for Japanese ≥ 90 mL/min/1.73 m2 at screening Subjects who is healthy, as judged by the investigator or sub-investigator based on physical examinations (subjective symptoms and objective findings) and all tests obtained at screening and during the period from hospital admission to immediately before study drug administration Exclusion Criteria: All subjects Received or is scheduled to receive any study drugs in other clinical trials or post-marketing studies within 120 days before screening or during the period from screening to the hospital admission day (Day -1) Deviate from the following provided range of blood pressure, pulse rate, body temperature and standard 12-lead ECG at screening or the hospital admission day (Day -1) Subjects who meet any of the criteria for laboratory tests at screening or the hospital admission day (Day -1). Normal ranges of each test specified at the study site or the test/assay organization will be used as the normal ranges in this study. Complication or history of drug allergies Developed upper gastrointestinal symptoms within 7 days before the hospital admission day (Day -1) Complication or history of hepatic disease Complication of long QT syndrome, congenital short QT syndrome A history of gastrointestinal resection Subjects with a complication or history of endocrine disease Subjects with a complication or history of malignant tumor Subjects with a complication or history of lymphatic disease 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, with regard to infection except for tuberculosis A complication or history of severe herpes zoster or herpes zoster disseminated At least twice of relapse of localized herpes zoster Inpatient hospital care for severe infectious diseases within 90 days before the hospital admission day (Day -1) Treatment with intravenous antibiotics within 90 days before the hospital admission day (Day -1) (prophylactic antibiotics are not applicable). Other than above, a subject with a high risk of developing infectious disease (e.g. subjects with urethral catheterisation) in judgment of the investigator or sub-investigator. Vaccination of live vaccines or live attenuated vaccines within 56 days before the hospital admission day (Day -1) (Inactivated vaccines such as influenza vaccine and pneumococcal vaccine are not applicable.) A history of clinically serious allergies Previously received administration of ASP015K Excessive alcohol drinking or smoking Patients with impaired renal function Patients who received or are scheduled to receive any new drugs within 14 days before the hospital admission day (Day -1) Patients who receive dialysis, or received renal transplantation Patients who developed acute changes in renal function and in all laboratory test results within 28 days before screening and patients with impaired renal function who may need new concomitant therapies during the study period. Patients with a complication of severe heart disease, NYHA class III or IV cardiac failure. Complication of alimentary disease, cerebrovascular disorder, respiratory disease Patients with tubular dysfunction, obvious urination impaired Subjects with normal renal function Subjects who received or is scheduled to receive medications (including over-the-counter [OTC] drugs) within seven days before the hospital admission day (Day -1). Subjects with a complication or history of heart disease, respiratory disease, alimentary disease, renal disease, endocrine disease, urological disease, cerebrovascular disorder

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control (Subjects with normal renal function)<br>Oral | Drug: ASP015K<br>* oral<br>|
| Experimental: Mild renal impairment<br>Oral | Drug: ASP015K<br>* oral<br>|
| Experimental: Moderate renal impairment<br>Oral | Drug: ASP015K<br>* oral<br>|
| Experimental: Severe renal impairment<br>Oral | Drug: ASP015K<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter of ASP015K: AUCinf | AUCinf: Area under the concentration-time curve from the time of dosing extrapolated to time infinity | 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 ASP015K: Cmax | Cmax: Maximum concentration | 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: 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 Adverse Events (AEs) |  | Up to 7 days after the study drug dosing | 
| Safety assessed by Vital signs | Supine blood pressure, supine pulse rate and axillary body temperature | Up to 7 days after the study drug dosing | 
| Safety assessed by Laboratory tests | Hematology, blood biochemistry and urinalysis | Up to 7 days after the study drug dosing | 
| Safety assessed by 12-lead ECGs | ECG: Electrocardiogram | Up to 7 days after the study drug dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of ASP015K: AUClast | AUClast: Area under the concentration-time curve from the time of dosing extrapolated to the last measurable concentration | 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 | t1/2: Terminal elimination half-life | 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: tmax | tmax: Time of 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 | 
| PK parameters of ASP015K: CL/F | CL/F: Apparent total systemic clearance | 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: Vz/F | Vz/F: Apparent volume of distribution during the terminal elimination phase | 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 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 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP015K, impaired renal function, Pharmacokinetics