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

NCT03960489 | Completed Phase 1 FDA Drug

• 2 other identifiers: 1517-CL-10012018-002924-18
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is 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 participants. This study will also 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) under fasting conditions in healthy male and female adult participants.

Conditions

Healthy Adult Subjects

Keywords

Pharmacokinetics; Tolerability; Safety; ASP1517; Roxadustat

Outcome Measures

Primary Outcomes (3)

• Area Under the Curve From Time of Dosing Extrapolated to Time Infinity (AUCinf) for Roxadustat

  AUCinf is defined as area under the plasma concentration versus time curve from time of dosing (pre-dose) to extrapolated infinite time (0-inf).

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Area Under the Concentration-Time Curve From the Time of Dosing to Last Measurable Concentration (AUClast) for Roxadustat

  AUClast is defined as area under the plasma concentration time-curve from time of dosing to the last measured concentration.

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Pharmacokinetics (PK) of Maximum Observed Concentration of Roxadustat

  Maximum observed concentration (Cmax) will be reported.

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

Secondary Outcomes (7)

• Percentage of the Area Under the Concentration-Time Curve From the Time of Dosing to Time infinity due to Extrapolation From the Last Measurable Concentration to Time Infinity (AUCinf[%extrap]) for Roxadustat

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Apparent Total Systemic Clearance of Roxadustat After Extravascular Dosing (CL/F)

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Terminal Elimination Half-life (t1/2) of Roxadustat

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Time to Reach Maximum Concentration (tmax) of Roxadustat

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

• Time Prior to the Time Corresponding to the First Measurable (nonzero) Concentration (tlag) of Roxadustat

  Predose (0 hour), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose on day 1

Study Arms (4)

Treatment Sequence 1 (ABCD)

EXPERIMENTAL

Participants will receive single dose of 100 mg roxadustat pediatric azo dye-free tablet (A), orally on day 1 in period 1 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet suspension (B), orally on day 1 in period 2 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet solid (C), orally on day 1 in period 3 followed by 100 mg roxadustat azo dye-containing tablet (D), orally on day 1 in period 4. Each period will be of 6 days. A washout period of 7 days will be included between each period.

Drug: Roxadustat

Treatment Sequence 2 (BDAC)

EXPERIMENTAL

Participants will receive 100 mg roxadustat pediatric azo dye-free mini-tablet suspension (B), orally on day 1 in period 1 followed by single dose of 100 mg roxadustat azo dye-containing tablet (D), orally on day 1 in period 2 followed by 100 mg roxadustat pediatric azo dye-free tablet (A), orally on day 1 in period 3 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet solid (C), orally on day 1 in period 4. Each period will be of 6 days. A washout period of 7 days will be included between each period.

Drug: Roxadustat

Treatment Sequence 3 (CADB)

EXPERIMENTAL

Participants will receive single dose of 100 mg roxadustat pediatric azo dye-free mini-tablet solid (C), orally on day 1 in period 1 followed by 100 mg roxadustat pediatric azo dye-free tablet (A), orally on day 1 in period 2 followed by 100 mg roxadustat azo dye-containing tablet (D), orally on day 1 in period 3 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet suspension (B), orally on day 1 in period 4. Each period will be of 6 days. A washout period of 7 days will be included between each period.

Drug: Roxadustat

Treatment Sequence 4 (DCBA)

EXPERIMENTAL

Participants will receive single dose of 100 mg roxadustat azo dye-containing tablet (D), orally on day 1 in period 1 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet solid (C), orally on day 1 in period 2 followed by 100 mg roxadustat pediatric azo dye-free mini-tablet suspension (B), orally on day 1 in period 3 followed by 100 mg of roxadustat pediatric azo dye-free tablet (A), orally on day 1 in period 4. Each period will be of 6 days. A washout period of 7 days will be included between each period.

Drug: Roxadustat

Interventions

Roxadustat DRUG

Participants will receive single dose of 100 mg azo dye free tablet or mini tablet suspension or solid mini tablet or dye containing tablet.

Also known as: ASP1517

Treatment Sequence 1 (ABCD); Treatment Sequence 2 (BDAC); Treatment Sequence 3 (CADB); Treatment Sequence 4 (DCBA)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Kyntra Bio: collaborator

Study Sites (1)

Site DE49001

Berlin, Germany

Location

MeSH Terms

Interventions

roxadustat

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: July 31, 2019
• Primary Completion: October 14, 2019
• Study Completion: October 14, 2019
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)