Last updated: 07/17/2024 17:34:50

Daprodustat bioequivalence and food effect study

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GSK study ID
207727
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Clinicaltrials.gov ID
NCT03493386
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EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A single centre, single dose, open-label, randomised, 2-way crossover study in healthy Japanese male subjects to evaluate the bioequivalence of daprodustat tablets (2 mg tablet vs. 4 mg tablet) (Part 1) and the food effect on the pharmacokinetics of daprodustat (Part 2)
Trial description: This is two-way crossover study to compare pharmacokinetic (PK) of daprodustat 2 milligram (mg) versus 4 mg tablets and food effect on the PK of daprodustat following single oral doses in healthy Japanese male subjects. This study will be conducted in two parts. Part 1 is the bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet in fasting and fed state in a crossover manner. There will 5-day wash-out period between each intervention period. There will be approximately 52 subjects in Part 1 and 12 subjects in Part 2. The study will last for 6 weeks.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Area under plasma concentration-time curve (AUC) from zero hours to last measurable concentration (AUC[0-t]) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed AUC(0-t) of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted AUC(0-t) of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Maximum plasma concentration (Cmax) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed Cmax of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted Cmax of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

AUC from zero hours extrapolated to infinity (AUC [0-inf]) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed AUC(0-inf) of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted AUC(0-inf) of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Time of occurrence of Cmax (Tmax) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed tmax of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted tmax of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Terminal phase half-life (T1/2) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed t1/2 of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted t1/2 of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Percentage of AUC (0-inf) obtained by extrapolation (percentage AUCex) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed percentage AUCex of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted percentage AUCex of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Apparent clearance (CL/F) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed CL/F of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted CL/F of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Apparent oral volume of distribution (Vz/F) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed Vz/F of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted Vz/F of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Elimination rate constant (kel) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed kel of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted kel of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Mean residence time (MRT) of daprodustat: Part 1

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fed MRT of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Fasted MRT of daprodustat: Part 2

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2.

Secondary outcomes:

Number of subjects with adverse events (AEs) and serious AEs (SAEs): Part 1

Timeframe: Up to Day 16

Number of subjects with AEs and SAEs: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal hematology parameters: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal hematology parameters: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal clinical chemistry parameters: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal clinical chemistry parameters: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal urinalysis: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal urinalysis: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) assessment : Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal SBP and DBP assessment : Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal pulse rate: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal pulse rate: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal body temperature: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal body temperature: Part 2

Timeframe: Up to Day 16

Number of subjects with abnormal 12-lead electrocardiogram (ECG) parameters: Part 1

Timeframe: Up to Day 16

Number of subjects with abnormal 12-lead ECG parameters: Part 2

Timeframe: Up to Day 16

Interventions:
  • Drug: Daprodustat 2 mg tablet
  • Drug: Daprodustat 4 mg tablet
    • Enrollment:
    64
    Primary completion date:
    2018-09-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Masanori Yamada, Minori Osamura, Hirofumi Ogura, Tomohiro Onoue, Akira Wakamatsu, Yotaro Numachi, Stephen Caltabiano, Kelly M. Mahar. A Single Dose, Open-label, Randomized, Two-way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat. Clin Pharmacol Drug Devel. 2020 DOI: 10.1002/cpdd.793
    Medical condition
    Anaemia
    Product
    daprodustat
    Collaborators
    Not applicable
    Study date(s)
    April 2018 to June 2018
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Male
    Age
    20 - 55 years
    Accepts healthy volunteers
    Yes
    • Subject must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
    • Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
    • History or presence of cardiovascular(CV), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
    • Abnormal blood pressure as determined by the investigator.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subject must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
    • Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
    • Body weight > = 50 kilogram (kg) and body mass index (BMI) within the range 18.5
    • 24.9 kilogram per meter square (kg/m^2).
    • Male subjects.
    • Subjects capable of giving signed informed consent.
    Exclusion criteria:
    • History or presence of cardiovascular(CV), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
    • Abnormal blood pressure as determined by the investigator.
    • ALT >1.5x upper limit of normal (ULN).
    • Bilirubin >1.5xULN
    • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • QTcF > 500 millisecond (msec). The QTcF is the QT interval corrected for heart rate according to Fridericia’s formula, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QT correction (QTc) for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
    • The values of Hgb at screening: >=16.0 gram per deciliter (g/dL).
    • History of deep vein thrombosis, pulmonary embolism or other thrombosis related condition.
    • History of myocardial infarction (MI) or acute coronary syndrome, stroke or transient ischemic attack.
    • Subjects that have undergone cholecystectomy.
    • History of malignancy within the prior 2 years or currently receiving treatment for cancer.
    • Any evidence of heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
    • Past or intended use of over-the-counter or prescription medication including vitamins, diet foods and herbal medications within 14 days prior to first dosing.
    • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
    • Current enrolment or past participation (that is administration of last dose of investigational study intervention) within the last 30 days (or 5 half-lives, whichever is longer) before signing of consent in this clinical study involving an investigational study intervention or any other type of medical research.
    • The subject with positive serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum haemagglutination test [TPHA]), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
    • Positive pre-study drug screen.
    • Regular alcohol consumption within 6 months prior to the study defined as:for an average weekly intake of >14 units for males. One unit is equivalent to 350 milliliter (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
    • Smoking or history of regular use of tobacco- or nicotine-containing products (example nicotine patch, electronic cigarette) within 6 months prior to screening.
    • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
    • History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL within 1 month prior to the first dosing day.

    Trial location(s)

    Location
    Status
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    Location
    GSK Investigational Site
    Fukuoka, Japan, 813-0017
    Status
    Study Complete
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    Study documents

    Study report synopsis
    Available language(s): English
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    Protocol
    Available language(s): English
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    Statistical analysis plan
    Available language(s): English
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    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2018-09-06
    Actual study completion date
    2018-09-06

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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