Clinical trial NCT04143477: A Study to Evaluate the Pharmacokinetics and Safety of ASP015K in Healthy Chinese Subjects
Official title: An Open-Label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics and Safety of ASP015K in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: peficitinib
ASP015K
pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2019-10-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the pharmacokinetics and safety of ASP015K after single-dose and multiple-dose administration in healthy Chinese participants.


Eligibility criteria: Inclusion Criteria:

* Normal Body Mass index (BMI) and weight: BMI\[= weight kg/(height m)\^2\] \> 19 kg/m\^2 and ≤ 24 kg/m\^2, the weight is no less than 50 kg for male and 45 kg for female at screening.
* Female subject must either: Be of non-childbearing potential, postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile. Or, if of childbearing potential: agree not to try to become pregnant during the study and for 60 days after the final study drug administration, must have a negative pregnancy at Screening and Day -1, and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at Screening and throughout the study period, and for 60 days after the final study drug administration.
* Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 60 days after the final study drug administration.
* Female subject must not donate ova starting at Screening and throughout the study period, and for 60 days after the final study drug administration.
* Male subject and female spouse/partners who are of childbearing potential must be using 1 form of highly effective birth control starting at Screening and throughout the study period, and for 90 days after the final study drug administration.
* Male subject must not donate sperm starting at Screening and throughout the study period, and for 90 days after the final study drug administration.
* Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until completion of the last study visit.

Exclusion Criteria:

* Female subject who has been pregnant within 6 months prior to screening or breast feeding within 3 months prior to screening.
* Subject has a known or suspected hypersensitivity to ASP015K, or any components of the formulation used.
* Subject has any of the liver chemistry tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], gamma-glutamyl transferase \[GGT\] and total bilirubin \[TBL\]) above the upper limit of normal on Day -1. In such a case, the assessment may be repeated once.
* Subjects who meet any of the following criterion for laboratory tests on Day -1. Normal ranges of each test specified at the study site or test/assay organization will be used as the normal ranges in this study. In such a case, the assessment may be repeated once.

  * Hematology: a deviation of +20% from the upper limit or -20% from the lower limit of the normal range, and clinically significant.
  * Blood biochemistry: a deviation from the normal range regarding serum creatinine, serum electrolytes (Na, K, and Cl), or fasting blood glucose; a deviation of +20% from the upper limit or -20% from the lower limit of the normal range regarding laboratory test items other than above, and clinically significant. However, the lower limit of the normal range will not be established for lactate dehydrogenase (LD), creatinine kinase (CK), total cholesterol, triglyceride, urea, serum creatinine, and uric acid, whose deviation from the lower limit is considered not clinically significant.
  * Urinalysis: a deviation from the normal range of each urinalysis test item.
* Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
* Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, respiratory,pulmonary, neurologic, cerebrovascular, lymphatic, dermatologic, psychiatric, renal, and/or other major disease or malignancy.
* Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to Day -1.
* Subject has any clinically significant abnormality in the physical examination, 12-lead electrocardiogram (ECG) and protocol defined clinical laboratory tests at Screening or Day -1.
* Subject has a pulse rate \< 45 or \> 100 bpm; systolic blood pressure (SBP) \> 140 mmHg; diastolic blood pressure (DBP) \> 90 mmHg (measurements taken after subject has been resting in sit position for 5 min; pulse will be measured automatically) at screening or on Day -1. If the pulse rate or blood pressure exceeds the limits above, 1 additional test can be taken.
* Subjects with abnormal body temperature, defined as axillary temperature \>37.3 ºC or \<35.0 ºC at Screening or Day -1.
* Subject has a corrected QT interval (QTcF) of \> 430 ms (for males) and \> 450 ms (for females) at screen or on Day -1(at screen and on Day-1, will be performed). If the QTcF exceeds the limits above on Day-1, 1 additional ECG test can be taken.
* Subject has any history or evidence of congenital short QT syndrome(defined as QTc \< 330 ms).
* Subject has any history of gastrointestinal resection (excepted appendectomy)..
* Subject has developed upper gastrointestinal symptoms within 1 week prior to Day -1.
* Subject applies to any of the following concerns with regard to tuberculosis.

  * History of active tuberculosis
  * Abnormalities detected in a chest X-ray test at Screening
  * Contact with infectious tuberculous patients
  * T-spot or Quantiferon Gold test show tuberculosisinfection positive.
* Subject applies to any of the following concerns with regard to infection other than tuberculosis.

  * 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 prior to Day -1
  * Treatment with intravenous antibiotics within 90 days prior to Day -1 (prophylactic antibiotics are not applicable).
  * Other than above, with a high risk of developing infectious disease (subjects with urethral catheterisation etc.).
* Subject has vaccination of live vaccines or live attenuated vaccines within 56 days prior to Day -1 (inactivated vaccines such as influenza vaccine and pneumococcal vaccines are not applicable.).
* Subject has used any prescribed or nonprescribed drugs (including vitamins or natural and herbal remedies, e.g. St. John's Wort) in the 2 weeks prior to study drug administration.
* Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.
* Subject has a history of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) (\> 14units of alcohol for female subjects) within 3 months prior to admission to the clinical unit or the subject tests positive for alcohol or drugs of abuse at Screening or Day -1 (amphetamines,barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates).
* Subject has used any drugs of abuse within 3 months prior to admission to the clinical unit.
* Subject has had significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to Day -1.
* Subject has a positive serology test for hepatitis B surface antigen (HBsAg), antihepatitis A virus (immunodeficiency virus \[Ig\]M), anti-hepatitis C virus, anti-hepatitis B core or antihuman immunodeficiency virus (HIV) at Screening.
* Subject has participated in any clinical study or has been treated with any investigational drugs within 3 moths prior to screening.
* Subject has any condition which makes the subject unsuitable for study participation.
* Subject is an employee of the Astellas Group, Clinical Research Organization (CRO) or the clinical unit.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to Day 20
measure: Number of participants with laboratory value abnormalities and/or AEs
timeFrame: Up to Day 20
measure: Number of participants with vital sign abnormalities and/or AEs
timeFrame: Up to Day 20
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
timeFrame: Up to Day 20
measure: Number of participants with physical examination abnormalities and/or AEs
timeFrame: Up to Day 20
measure: Pharmacokinetics (PK) of peficitinib: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
timeFrame: On Day 1
measure: PK of peficitinib: AUC from the time of dosing to the last measurable concentration (AUClast)
timeFrame: On Day 1 and 8
measure: PK of peficitinib: AUC from the time of dosing to 24 hours post dose (AUC24h)
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib: Apparent total systemic clearance after extravascular dosing (CL/F)
timeFrame: On Day 1 and 13
measure: PK of peficitinib: Maximum concertation (Cmax)
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib: Terminal elimination rate constant (Lambdaz)
timeFrame: On Day 1 and 13
measure: PK of peficitinib: Terminal elimination half-life (t1/2)
timeFrame: On Day 1 and 13
measure: PK of peficitinib: Time of the maximum concentration (tmax)
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib: Apparent volume of distribution during the terminal elimination phase after single extravascular dosing (VzF)
timeFrame: On Day 1
measure: PK of peficitinib: Concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: On Day 9 to 12 and 13
measure: PK of peficitinib: Concentration at 24 hours post dosing (C24h)
timeFrame: On Day 13
measure: PK of peficitinib: Peak trough ratio (PTR)
timeFrame: On Day 13
measure: PK of peficitinib: Accumulation ratio calculated using AUC (Rac(AUC24h))
timeFrame: On Day 13
measure: PK of peficitinib: Accumulation ratio calculated using the maximum concentration (Rac (Cmax))
timeFrame: On Day 13
measure: PK of peficitinib metabolite: AUCinf
timeFrame: On Day 1
measure: PK of peficitinib metabolite: AUClast
timeFrame: On Day 1 and 8
measure: PK of peficitinib metabolite: AUC24h
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib metabolite: Cmax
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib metabolite: Lambdaz
timeFrame: On Day 1 and 13
measure: PK of peficitinib metabolite: t1/2
timeFrame: On Day 1 and 13
measure: PK of peficitinib metabolite: tmax
timeFrame: On Day 1, 8 and 13
measure: PK of peficitinib metabolite: Ctrough
timeFrame: On Day 9 to 12 and 13
measure: PK of peficitinib metabolite: C24h
timeFrame: On Day 13
measure: PK of peficitinib metabolite: PTR
timeFrame: On Day 13
measure: PK of peficitinib metabolite: Rac(AUC24h)
timeFrame: On Day 13
measure: PK of peficitinib metabolite: Rac(Cmax)
timeFrame: On Day 13
measure: PK of peficitinib metabolite: Metabolite to parent ratio of the area under the concentration-time curve corrected by the molecular weight ratio of parent to metabolite (MPR)
timeFrame: On Day 1, 8 and 13
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Site CN86001
Study officials:
affiliation: Astellas Pharma China, Inc.
name: Medical Moniter, Senior Manager
role: STUDY_DIRECTOR
References:
citation: Gao X, He X, Oshima H, Miyatake D, Otsuka Y, Kato K, Cai C, Wojtkowski T, Song N, Kaneko Y, Shi A. Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healthy Chinese Subjects. Drug Des Devel Ther. 2022 May 9;16:1365-1381. doi: 10.2147/DDDT.S359501. eCollection 2022.