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

Healthy Adult Subjects Clinical Trial

Official title:

A Phase 1 Crossover Study to Assess the Relative Bioavailability of Roxadustat Following a Single Dose of Pediatric Azo Dye-free Tablet and Pediatric Azo Dye-free Mini-tablet (Solid and Suspension) Compared to a Single Dose of Azo Dye-containing Tablet in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03960489
• Other study ID #: 1517-CL-1001
• Secondary ID: 2018-002924-18
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2019
• Est. completion date: October 14, 2019

Study information

• Verified date: October 2020
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 14, 2019
• Est. primary completion date: October 14, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Adult Subjects

Intervention

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

Locations

Country	Name	City	State
Germany	Site DE49001	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	FibroGen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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	AUC%extrap is defined as the percentage of AUC [0-8] obtained by forward extrapolation. It will be calculated as (AUC [0-8] minus AUClast)*100/ AUC [0-8], where AUC [0-8] = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-8) and AUClast is area under the plasma concentration time-curve from zero (pre-dose) 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
Secondary	Apparent Total Systemic Clearance of Roxadustat After Extravascular Dosing (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.	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	Terminal Elimination Half-life (t1/2) of Roxadustat	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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	Time to Reach Maximum Concentration (tmax) of Roxadustat	Time to reach maximum concentration of roxadustat following drug administration 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	Time Prior to the Time Corresponding to the First Measurable (nonzero) Concentration (tlag) of Roxadustat	Tlag is defined as the time prior to the time corresponding to the first measurable 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
Secondary	Apparent Volume of Distribution During the Terminal Elimination Phase After Extravascular Dosing (Vz/F) of Roxadustat	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	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	Number of Participants With Treatment-Emergent Adverse Event (TEAEs)	An AE is defined as any untoward medical occurrence in a participant who will be given the study drug or who has undergone study procedures and did not necessarily has a causal relationship with this treatment. An AE could therefore be any unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A treatment-emergent adverse event is defined as an adverse event with onset at any time from dosing until the last scheduled procedure.	From first dose of study drug up to end of study visit (up to 54 days)