| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy Adult Volunteers (intended indication is anemia associated with chronic kidney disease (CKD)) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Healthy Adult Volunteers (intended indication is anemia due to chronic kidney disorders) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10002272 |
| E.1.2 | Term | Anemia |
| E.1.2 | System Organ Class | 100000004851 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the relative bioavailability of single doses of 100 mg roxadustat pediatric azo dye-free tablet and 100 mg roxadustat pediatric azo dye-free mini-tablet (solid and suspension) (new formulations) compared to 100 mg roxadustat azo dye-containing tablet (reference formulation) under fasting conditions in healthy male and female adult subjects. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of single doses of 100 mg roxadustat pediatric azo dye-free tablet and 100 mg roxadustat pediatric azo dye-free mini-tablet (solid and suspension) (new formulations) and a single dose of 100 mg roxadustat azo dye-containing tablet (reference formulation) in healthy male and female adult subjects.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Institutional review board/independent ethics committee-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US sites) must be obtained and signed by the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is a healthy male or female adult subject between 18 to 45 years of age, inclusive at screening.
3. Subject has a body mass index range of 18.5 to 30.0 kg/m2 , inclusive and weighs at least 50 kg at screening.
4. A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) OR
b. WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 28 days after the final study drug administration.
5. 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.
6. Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
7. 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.
8. A male subject must not donate sperm during the treatment period and for at least 28 days after the final study drug administration.
9. 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.
10. Subject agrees not to participate in another interventional study while participating in the present study. |
|
| E.4 | Principal exclusion criteria |
1. Subject has received any investigational study drug within 28 days or 5 half-lives, whichever is longer, prior to screening.
2. Subject has any condition which, in the investigator’s opinion, makes the subject unsuitable for study participation.
3. Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
4. Subject has a known or suspected hypersensitivity to roxadustat or any components of the formulation used.
5. Subject has had previous exposure with roxadustat.
6. 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.
7. 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.
8. 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, as judged by the investigator.
9. Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day -1.
10. Subject has any clinically significant abnormality following the investigator’s review of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
11. 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.
12. 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.
13. 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.
14. Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months prior to screening.
15. 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.
16. Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) within 3 months prior to day -1.
17. Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
18. Subject has consumed grapefruit, Seville oranges, grapefruit-containing products or Seville orange-containing products within 72 hours prior to day -1.
19. 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.
20. 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.
21. Subject is an employee of Astellas or the clinical site.
22. 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).
23. Subject has abnormal renal function, indicated by creatinine above the ULN or chronic kidney disease epidemiology collaboration (CKD EPI) based estimated glomerular filtration rate (eGFR) < 90 mL/min [Appendix 12.10 Chronic Kidney Disease Epidemiology Collaboration Formulas] on day -1. In such a case, the assessment may be repeated once. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacokinetics:
- Roxadustat plasma: AUC inf, AUC last and C max |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to day 4 in each treatment period
|
|
| E.5.2 | Secondary end point(s) |
Pharmacokinetics:
- AUC inf (%extrap), CL/F, t½, t max, t lag and V z/F
Safety and tolerability:
- Nature, frequency and severity of AEs
- Clinical laboratory tests (hematology, biochemistry and urinalysis)
- Vital signs (blood pressure and pulse) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetics: Up to day 4 in each treatment period / Safety and tolerability: Up to day 46
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Pharmacokinetic, Pharmacogenetic |
|
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
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