AnaemiaPhase 1NCT03223337

Daprodustat Hepatic Impairment Study

A Phase 1 study testing Daprodustat (GSK1278863) in people with Anaemia, run by GlaxoSmithKline at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Anaemia
What is being tested?: Daprodustat (GSK1278863)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 2 sitesUnited States
Study dates: 24 Jul 2017to 20 Aug 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

For all subjects:
Subject must be at least 18 years of age inclusive, at the time of signing the informed consent.
Hemoglobin values at screening <=16.0 gram per deciliter (g/dL) for males and <=14.0 g/dL for females.
Body weight >=45 kilograms (kg) and body mass index (BMI) within the range 18-40 kg per meter square (kg/m^2) (inclusive).
Male or female subjects will be included. A female subject is eligible to participate if she is not breastfeeding, and at least one of the following applies: Not pregnant as confirmed by two pregnancy tests; Not a woman of childbearing potential (WOCBP); For WOCBP that are currently utilizing a highly-effective contraceptive method prior to enrolment, agrees to follow the contraceptive guidance during the treatment period to the follow-up visit.
Capable of giving signed informed consent form.

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Additional inclusion criteria for Hepatically-Impaired subjects:
Subjects in Part 1 with Moderate Hepatic Impairment Only (Cohort 1): Is considered to have moderate hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having moderate hepatic impairment, subjects must have a Child-Pugh (Class B) score of 7-9 AND previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computerized tomography (CT) scan, magnetic resonance imaging (MRI) or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension).
Subjects in Part 2 with Mild OR Severe Hepatic Impairment Only (Cohort 3; if conducted): Is considered to have mild or severe hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having mild OR severe hepatic impairment, subjects must have: classified as having mild hepatic impairment, subjects must have a Child- Pugh (Class A) score of 5-6 AND previous confirmation of chronic liver disease by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension); classified as having severe hepatic impairment, subjects must have Child- Pugh (Class C) score of 10-13 AND previous confirmation of chronic liver disease by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension).
Supplemental inclusion criteria for ALL hepatically-impaired subjects: Chronic (>6 months), stable (no acute episodes of illness due to deterioration in hepatic function within the previous 1 month prior to screening) hepatic impairment due to any etiology. Subjects must also remain stable throughout the Screening period. Assessment of the stability of the subjects hepatic function will be determined by the investigator.
Additional inclusion criteria for healthy control subjects:
Healthy control subjects will be matched for age +/-10 years to subjects in the respective hepatic impairment cohort but must also be at least 18 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator and/or the Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Healthy control subjects will be matched for BMI +/-15% to subjects in the respective hepatic impairment cohort but must also remain in the range of body weight >=45 kg and BMI within the range 18-38 kg/m^2 (inclusive).

Who cannot join

For all subjects:
QT interval corrected for heart rate according to Fridericia's formula (QTcF) >500 milliseconds (msec).
Recent history of deep vein thrombosis, pulmonary embolism or other thrombosis related condition. Any prior medical history in these areas will be reviewed and approved by the PI and the sponsor's Medical Monitor on a case by case basis as needed.
Myocardial infarction or acute coronary syndrome, stroke or transient ischemic attack within the 12 weeks prior to enrollment.
Subjects with a pre-existing condition (other than liver disease) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of daprodustat.
Subjects that have undergone cholecystectomy within the past 3 months.

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Subjects with chronic inflammatory joint disease (example, scleroderma, systemic lupus erythematosis, rheumatoid arthritis).
History of malignancy within the prior 2 years or known kidney mass >3 centimeter (cm) (end stage renal disease subjects with impairment only) OR currently receiving treatment for cancer. ONLY exception is localized squamous cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to enrollment.
Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
Current enrolment or past participation (i.e., administration of last dose of investigational study treatment) within the last 30 days (or 5 half-lives, whichever is longer) before Day 1 in this or any other clinical study involving an investigational study treatment or any other type of medical research.
Present of 8 times Upper limit of normal (ULN) elevations in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or bilirubin.
Subjects with any other medical condition which, in the judgment of the investigator and Medical Monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject.
Subjects with advanced ascites (Grade 3).
Subjects with refractory encephalopathy as judged by the investigator or significant Central Nervous System (CNS) disease (example dementia, or seizures) which the investigator considers will interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
Subjects with functional Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
Presence of hepatopulmonary or hepatorenal syndrome.
Presence of primarily cholestatic liver diseases.
History of liver transplantation.
Subjects with signs of active infection, including active spontaneous bacterial peritonitis.
Subjects with unstable cardiac function or subjects with hypertension whose blood pressure is not controlled (based on the investigator's discretion).
Diabetic subjects whose diabetes is not controlled (based on the investigator's discretion).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Presence of Hepatitis B surface antigen (HBsAg) at screening or Positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.
Positive pre-study drug/alcohol screen.
Positive human immunodeficiency virus (HIV) antibody test.
Regular use of known drugs of abuse.
Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 drinks. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Non-randomized, Parallel Group, Single-dose Adaptive Study in Adults With Hepatic Impairment and Matched, Healthy Control Participants With Normal Hepatic Function

Daprodustat (GSK1278863), is a small molecule currently in development for the treatment of anemia of chronic kidney disease (CKD). Results of the earlier studies shows that liver is involved in the clearance of Daprodustat and hence, hepatic impairment can affect Daprodustat levels in the body. This single dose study will assess the effect of liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD) of daprodustat. The study will be conducted in two parts, Part 1 will include subjects with moderate hepatic impairment and matched healthy control subjects whereas Part 2 will include subjects will either mild or severe hepatic impairment and matched healthy control subjects. Approximately 8 subjects will be included in each of the group and all subjects will receive 6 milligram (mg) of daprodustat as a single oral dose in the fasted state. Total duration of participation in the study for a subject will be up to 7 weeks.

Conditions: Anaemia
Being tested: Daprodustat (GSK1278863)
Keywords: GSK1278863, Daprodustat, Healthy control, Single dose, Hepatic Impairment
Medical subject headings: Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Daprodustat (GSK1278863)Drug
Daprodustat (GSK1278863) 6 mg tablet will be given to all subjects as a single dose via oral route. Daprodustat (GSK1278863) is a 9.0 millimeter (mm) round, compound radius, white film coated tablet.

Study groups in NCT03223337
Study group	Role	What they receive
Subjects with moderate hepatic impairment: Part 1	Experimental	Approximately 8 subjects with moderate hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 7, one with a score of 8 and one with a score of 9. The group will also include at least one female and at least one male subject. Receives: Drug: Daprodustat (GSK1278863)
Matched Healthy controls: Part 1	Active comparator	Approximately 8 healthy controls, matched in gender, age and BMI to subjects with moderate hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject. Receives: Drug: Daprodustat (GSK1278863)
Subjects with either mild or severe hepatic impairment: Part 2	Experimental	Approximately 8 subjects with mild or severe hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 5 and one with a score of 6 for mild hepatic impairment and at least one subject with a Child-Pugh score of 10 or 11 and one with a score of 12 or 13 for severe hepatic impairment. The group will also include at least one female and at least one male subject. Receives: Drug: Daprodustat (GSK1278863)
Matched healthy controls: Part 2	Active comparator	Approximately 8 healthy controls, matched in gender, age and BMI to subjects with mild or severe hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject. Receives: Drug: Daprodustat (GSK1278863)

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2) , GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: Cmax of GSK1278863 and Its Metabolites.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: T1/2 of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 2: Tmax of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: 3 hours, 12 hours and 24 hours post-dose
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Measured: 3 hours, 12 hours and 24 hours post-dose
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818, GSK2506102, GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Measured: 3 hours, 12 hours and 24 hours post-dose
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites (GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13)). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Measured: 3 hours, 12 hours and 24 hours post-dose

Secondary outcomes (14)

Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points. Pharmacodynamic Population comprised of all participants in the Safety Population who had at least one pharmacodynamic assessment.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: Cmax, EPO Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: Tmax, EPO Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: AUC (0-t, EPO) Following Administration of GSK1278863
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Measured: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study medication.
Measured: Up to 16 days
Part 2: Number of Participants With AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment.
Measured: Up to 16 days
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were <0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, <3 or >20 x10^9 cells per liter (cells/L) for leukocytes, <0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, and <100 or >550 x10^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Measured: Baseline (Screening) and up to Day 16
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were <0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 g/L for hemoglobin, <3 or >20 x10^9 cells/L for leukocytes, <0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, and <100 or >550 x10^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Measured: Baseline (Screening) and up to Day 16
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of following parameters. PCI ranges were <30g/L (albumin), <2 or >2.75 millimoles/L(mmol/L) (calcium), <3 or >9mmol/L(glucose), >=2 times Upper limit of Normal(ULN) units/L(U/L) (alanine aminotransferase [ALT]), >=2 times ULN U/L (alkaline phosphatase), >=2 times ULN U/L(aspartate aminotransferase [AST]), >=1.5 times ULN micromoles/L (µmol/L)(bilirubin), <3 or >5.5mmol/L(potassium), and <130 or >150mmol/L(sodium). Participants were counted in worst case category that their value changes to (low,within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Measured: Baseline (Screening) and up to Day 16
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of following parameters. PCI ranges were <30g/L (albumin), <2 or >2.75 mmol/L (calcium), <3 or >9mmol/L (glucose), >=2 times ULN U/L (ALT), >=2 times ULN U/L (alkaline phosphatase), >=2 times ULN U/L (AST), >=1.5 times ULN µmol/L (bilirubin), <3 or >5.5 mmol/L (potassium), and <130 or >150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Measured: Baseline (Screening) and up to Day 16
Part 1: Number of Participants With Abnormal Urinalysis Findings
Urine samples were collected at indicated time points for the analysis of urine parameters including specific gravity and Potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine.
Measured: Up to Day 16
Part 2: Number of Participants With Abnormal Urinalysis Findings
Urine samples were collected at indicated time points for the analysis of urine parameters including specific gravity and Potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine.
Measured: Up to Day 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jul 201720 Aug 2018

First posted21 Jul 2017
Study start24 Jul 2017
Primary completion20 Aug 2018
Study completion20 Aug 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for AnaemiaStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: All subjects will receive 6 mg of daprodustat as a single oral dose in parallel way throughout the study period.
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03223337
Sponsor's protocol ID: 200231
Status last verified: Aug 2019
First submitted: 18 Jul 2017
Last updated: 4 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Mahar KM, Shaddinger BC, Ramanjineyulu B, Andrews S, Caltabiano S, Lindsay AC, Cobitz AR. Pharmacokinetics of Daprodustat and Metabolites in Individuals with Normal and Impaired Hepatic Function. Clin Pharmacol Drug Dev. 2022 May;11(5):562-575. doi: 10.1002/cpdd.1090. Epub 2022 Mar 30.
PubMed 35355447

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All Anaemia trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Non-randomized, Parallel Group, Single-dose Adaptive Study in Adults With Hepatic Impairment and Matched, Healthy Control Participants With Normal Hepatic Function
ClinicalTrials.gov ID: NCT03223337
Acronym / sponsor ID: 200231
Conditions: Anaemia
Keywords: GSK1278863, Daprodustat, Healthy control, Single dose, Hepatic Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 24 Jul 2017 (actual)
Primary completion: 20 Aug 2018 (actual)
Study completion: 20 Aug 2018 (actual)
First posted: 21 Jul 2017 (actual)
Results: Posted 4 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4
Model description: All subjects will receive 6 mg of daprodustat as a single oral dose in parallel way throughout the study period.

Arm	Type	Receives
Subjects with moderate hepatic impairment: Part 1	Experimental	Drug: Daprodustat (GSK1278863)Approximately 8 subjects with moderate hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 7, one with a score of 8 and one with a score of 9. The group will also include at least one female and at least one male subject.
Matched Healthy controls: Part 1	Active comparator	Drug: Daprodustat (GSK1278863)Approximately 8 healthy controls, matched in gender, age and BMI to subjects with moderate hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject.
Subjects with either mild or severe hepatic impairment: Part 2	Experimental	Drug: Daprodustat (GSK1278863)Approximately 8 subjects with mild or severe hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 5 and one with a score of 6 for mild hepatic impairment and at least one subject with a Child-Pugh score of 10 or 11 and one with a score of 12 or 13 for severe hepatic impairment. The group will also include at least one female and at least one male subject.
Matched healthy controls: Part 2	Active comparator	Drug: Daprodustat (GSK1278863)Approximately 8 healthy controls, matched in gender, age and BMI to subjects with mild or severe hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Subject must be at least 18 years of age inclusive, at the time of signing the informed consent.
Hemoglobin values at screening <=16.0 gram per deciliter (g/dL) for males and <=14.0 g/dL for females.
Body weight >=45 kilograms (kg) and body mass index (BMI) within the range 18-40 kg per meter square (kg/m^2) (inclusive).
Male or female subjects will be included. A female subject is eligible to participate if she is not breastfeeding, and at least one of the following applies: Not pregnant as confirmed by two pregnancy tests; Not a woman of childbearing potential (WOCBP); For WOCBP that are currently utilizing a highly-effective contraceptive method prior to enrolment, agrees to follow the contraceptive guidance during the treatment period to the follow-up visit.
Capable of giving signed informed consent form.

Key exclusion criteria (27 listed)

QT interval corrected for heart rate according to Fridericia's formula (QTcF) >500 milliseconds (msec).
Recent history of deep vein thrombosis, pulmonary embolism or other thrombosis related condition. Any prior medical history in these areas will be reviewed and approved by the PI and the sponsor's Medical Monitor on a case by case basis as needed.
Myocardial infarction or acute coronary syndrome, stroke or transient ischemic attack within the 12 weeks prior to enrollment.
Subjects with a pre-existing condition (other than liver disease) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of daprodustat.
Subjects that have undergone cholecystectomy within the past 3 months.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Daprodustat (GSK1278863)Daprodustat (GSK1278863) 6 mg tablet will be given to all subjects as a single dose via oral route. Daprodustat (GSK1278863) is a 9.0 millimeter (mm) round, compound radius, white film coated tablet.	Drug	Matched Healthy controls: Part 1, Matched healthy controls: Part 2, Subjects with either mild or severe hepatic impairment: Part 2, Subjects with moderate hepatic impairment: Part 1

Primary outcome

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2) , GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Cmax of GSK1278863 and Its Metabolites.
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: T1/2 of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Tmax of GSK1278863 and Its Metabolites
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Time frame: 3 hours, 12 hours and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Time frame: 3 hours, 12 hours and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Time frame: 3 hours, 12 hours and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818, GSK2506102, GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Time frame: 3 hours, 12 hours and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites (GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13)). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.

14 secondary outcomes

Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: Cmax, EPO Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: Tmax, EPO Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 2: AUC (0-t, EPO) Following Administration of GSK1278863
Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 16 days
Part 2: Number of Participants With AEs and SAEs
Time frame: Up to 16 days
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to Day 16
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to Day 16
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to Day 16
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to Day 16
Part 1: Number of Participants With Abnormal Urinalysis Findings
Time frame: Up to Day 16
Part 2: Number of Participants With Abnormal Urinalysis Findings
Time frame: Up to Day 16

Results and safety

Results posted to the registry on 4 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Moderate Hepatic Impairment Participants	8	8
Part 1: Healthy Participants	8	8
Part 2: Mild Hepatic Impairment Participants	0	0
Part 2: Healthy Participants	0	0

Primary outcome: Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Hour*nanogram per milliliter

Measure	Part 1: Moderate Hepatic Impairment Participants n = 8	Part 1: Healthy Participants n = 8
GSK1278863	296.2407 (111.1)	148.3225 (31.7)
GSK2391220 (M2)	77.6352 (56.9)	47.1340 (30.9)
GSK2487818 (M4)	47.5557 (67.4)	28.9896 (30.3)
GSK2506102 (M5)	16.8212 (43.9)	11.2658 (29.4)
GSK2506104 (M3)	NA (NA)	NA (NA)
GSK2531398 (M6)	33.9398 (49.2)	20.9224 (27.7)
GSK2531401 (M13)	52.0606 (34.0)	39.6044 (32.1)

Part 1: Moderate Hepatic Impairment Participants vs Part 1: Healthy Participants: Ratio of Geometric Least Square(LS) Mean: 1.9973 (90% CI 1.1063 to 3.6057)
Part 1: Moderate Hepatic Impairment Participants vs Part 1: Healthy Participants: Ratio of Geometric LS Mean: 1.6471 (90% CI 1.1267 to 2.4079)
Part 1: Moderate Hepatic Impairment Participants vs Part 1: Healthy Participants: Ratio of Geometric LS Mean: 1.6404 (90% CI 1.0744 to 2.5048)

Population analysed: Pharmacokinetic Population

Primary outcome: Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites

Measure	Part 2: Mild Hepatic Impairment Participants n = 8	Part 2: Healthy Participants n = 7
GSK1278863	299.8773 (39.9)	205.7559 (37.2)
GSK2391220 (M2)	91.3799 (44.7)	47.1647 (26.9)
GSK2487818 (M4)	63.6211 (40.1)	31.7637 (28.4)
GSK2506102 (M5)	19.4020 (36.6)	11.3374 (26.7)
GSK2506104 (M3)	91.7692 (41.0)	50.1154 (28.3)
GSK2531398 (M6)	41.4666 (31.2)	21.0066 (23.5)
GSK2531401 (M13)	46.7001 (66.5)	31.9797 (40.9)

Part 2: Mild Hepatic Impairment Participants vs Part 2: Healthy Participants: Ratio of Geometric LS Mean: 1.4574 (90% CI 1.0350 to 2.0523)
Part 2: Mild Hepatic Impairment Participants vs Part 2: Healthy Participants: Ratio of Geometric LS Mean: 1.9375 (90% CI 1.3919 to 2.6968)
Part 2: Mild Hepatic Impairment Participants vs Part 2: Healthy Participants: Ratio of Geometric LS Mean: 1.8312 (90% CI 1.3342 to 2.5133)

Population analysed: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Primary outcome: Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose. Mean (Standard Deviation). Unit: Percentage of AUCex

Measure	Part 1: Moderate Hepatic Impairment Participants n = 8	Part 1: Healthy Participants n = 8
GSK1278863	0.0463 (0.03971)	0.0486 (0.03445)
GSK2391220 (M2)	0.1919 (0.14164)	0.4176 (0.38893)
GSK2487818 (M4)	0.5756 (0.89564)	0.6763 (0.61031)
GSK2506102 (M5)	0.6147 (0.17403)	2.1559 (2.01781)
GSK2506104 (M3)	NA (NA)	NA (NA)
GSK2531398 (M6)	0.2598 (0.10004)	0.3689 (0.26189)
GSK2531401 (M13)	0.2983 (0.27141)	0.2787 (0.15617)

Population analysed: Pharmacokinetic Population

Primary outcome: Part 2: Percentage AUCex of GSK1278863 and Its Metabolites

Measure	Part 2: Mild Hepatic Impairment Participants n = 8	Part 2: Healthy Participants n = 7
GSK1278863	0.1148 (0.26035)	0.0601 (0.06032)
GSK2391220 (M2)	0.2943 (0.32698)	0.8105 (1.60084)
GSK2487818 (M4)	0.2584 (0.30727)	0.9054 (0.89147)
GSK2506102 (M5)	0.5138 (0.22859)	1.5924 (1.69300)
GSK2506104 (M3)	0.2565 (0.28382)	0.6875 (1.33005)
GSK2531398 (M6)	0.2915 (0.25350)	0.9412 (0.94415)
GSK2531401 (M13)	0.2327 (0.23338)	0.5256 (0.46352)

Population analysed: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 16 days in each part of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Moderate Hepatic Impairment Participants	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Part 1: Healthy Participants	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Part 2: Mild Hepatic Impairment Participants	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Part 2: Healthy Participants	0 of 9 (0%)	0 of 9 (0%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35355447Mahar KM, Shaddinger BC, Ramanjineyulu B, Andrews S, Caltabiano S, Lindsay AC, Cobitz AR. Pharmacokinetics of Daprodustat and Metabolites in Individuals with Normal and Impaired Hepatic Function. Clin Pharmacol Drug Dev. 2022 May;11(5):562-575. doi: 10.1002/cpdd.1090. Epub 2022 Mar 30.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daprodustat (GSK1278863) in people with Anaemia, run by GlaxoSmithKline at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites (time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03223337, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019.