A Study to Assess the Relative Bioavailability of Roxadustat Following a Single Dose of Pediatric Azo Dye-free Tablet Formulation and Pediatric Azo Dye-free Mini-tablet Formulation Compared to a Single Dose of Azo Dye-containing Tablet Formulation in Healthy Adult Subjects

This is a 4-period, 4-sequence single dose crossover study. Each participant will participate in 4 treatment periods separated by a washout of at least 7 days between study drug administrations in each period. Participants will be randomized to 1 of 4 sequences.

Participants will be screened for up to 21 days prior to study drug administration on day 1 of period 1. Eligible participants will be admitted to the clinical unit on day -1 of each period and will be residential for 5 days/4 nights.

Participants will receive a single dose of 100 mg roxadustat pediatric azo dye-free tablet, 100 mg roxadustat pediatric azo dye-free mini-tablet (suspension), 100 mg roxadustat pediatric azo dye-free mini-tablet (solid) (new formulations) or 100 mg roxadustat azo dye-containing tablet (reference formulation) under fasting conditions on day 1 of each period.

Inclusion criteria

• Subject has a body mass index range of 18.5 to 30.0 kg/m2, inclusive and weighs at least 50 kg at screening.
• A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

• Not a woman of childbearing potential (WOCBP), or
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 28 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
• A male subject with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 28 days after the final study drug administration.
• A male subject must not donate sperm during the treatment period and for at least 28 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner(s) is (are) breastfeeding throughout the study period and for 28 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion criteria

• Subject has received any investigational study drug within 28 days or 5 half lives, whichever is longer, prior to screening.
• Subject has any condition which makes the subject unsuitable for study participation.
• Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to roxadustat or any components of the formulation used.
• Subject has had previous exposure with roxadustat.
• Subject has any of the liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, gamma-glutamyl transferase and total bilirubin [TBL]) above the upper limit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to study drug administration.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, 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 of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
• Subject has a mean pulse < 50 or > 90 bpm; mean systolic blood pressure > 140 mmHg; mean diastolic blood pressure > 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) on day -1. If the mean blood pressure exceeds the limits above, 1 additional measurement in triplicate can be taken.
• Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of > 430 msec (for male subjects) and > 450 msec (for female subjects) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
• Subject has used any prescribed or nonprescribed drugs (including vitamins, calcium and iron supplements, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day), topical dermatological products, including corticosteroid products, hormonal contraceptives and hormone replacement therapy.
• Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months prior to screening.
• Subject has a history of drinking more than 24 g/day of alcohol (10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) (> 12 g/day of alcohol for female subjects) within 3 months prior to day -1 or the subject tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1.
• Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) within 3 months prior to day -1.
• Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
• Subject has consumed grapefruit, Seville oranges, grapefruit-containing products or Seville orange-containing products within 72 hours prior to day -1.
• 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, hepatitis B core antibodies, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies or antibodies to human immunodeficiency virus type 1 and/or type 2 at screening.
• Subject is an employee of Astellas or the clinical site.
• Subject is a vulnerable subject (e.g., subject kept in detention, protected adult under guardianship/trusteeship, soldier or committed to an institution by governmental or juridical order).
• Subject has abnormal renal function, indicated by creatinine above the ULN or chronic kidney disease epidemiology collaboration based estimated glomerular filtration rate (eGFR) < 90 mL/min on day 1. In such a case, the assessment may be repeated once.