AzTrials
AzTrials

AnaemiaPhase 1NCT03239522

Absorption and Elimination of Radiolabeled Daprodustat

A Phase 1 study testing [14C]-GSK1278863 solution for IV infusion, [14C]-GSK1278863 oral solution and Daprodustat 6 mg oral tablet in people with Anaemia, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

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

Official record
Search all trials

Trial summary

Absorption, metabolism and excretion of daprodustat (GSK1278863) have been studied in previous clinical trials; however, the elimination routes and metabolic pathways of daprodustat have not been fully elucidated in humans. Read more about this study

Who is it for?
Ages 30 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Anaemia
What is being tested?
[14C]-GSK1278863 solution for IV infusion, [14C]-GSK1278863 oral solution and Daprodustat 6 mg oral tablet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited Kingdom
Study dates
10 Oct 2017to 28 Nov 2017
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 30 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Aged 30 to 55 years, 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, vital signs, laboratory tests, and ECG. A participant with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Hemoglobin value at screening greater than the lower limit of the laboratory reference range and less than or equal to 16.0 gram (g) per deciliter (dL).
  • History of regular bowel movements (averaging one or more bowel movements per day).
  • Non-smoker, or ex-smoker who hasn't regularly smoked for the 6 months before screening.
  • Body weight of 50 kilogram (kg) and above, and body mass index (BMI) within the range 19.0-31 kg per meter (m)^2 (inclusive).
Show all 9Show fewer
  • Participants must agree to use contraception as follows: participants with female partners of childbearing potential must agree to use a condom from the time of first dose of study treatment until 1 month after their last dose.
  • Capable of giving signed informed consent.
  • Willingness to give written consent to have data entered into The Over-volunteering Prevention System.

Who cannot join

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Participants with a history of cholecystectomy must be excluded.
  • Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead ECG.
  • Myocardial infarction or acute coronary syndrome <=12 weeks prior to screening through to enrollment (Day 1, treatment period 1).
  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, or which could constitute a risk when taking the study treatment, or interfere with the interpretation of data.
  • Evidence of actively bleeding gastric, duodenal or esophageal ulcer disease OR clinically significant GI bleeding <=12 weeks prior to screening through to enrollment (Day 1, treatment period 1).
  • History of malignancy within the two years before dosing, with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to screening; currently receiving treatment for cancer; has a strong family history of cancer (e.g., familial cancer disorders).
Show all 32Show fewer
  • Mentally or legally incapacitated.
  • Heart Failure: Class II, III or IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
  • Daprodustat is a substrate of cytochrome P4502C8 (CYP2C8). Co-administration of drugs that are inhibitors of this enzyme are prohibited.
  • Past or intended use of over-the-counter or prescription medication including herbal medications prior to dosing except occasional use of paracetamol (acetaminophen), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the follow-up visit, unless in the opinion of the investigator and GSK medical monitor the medication will not interfere with the study.
  • Current enrolment in a clinical trial; recent participation in a clinical trial and has received an investigational product within 3 months before their first dose in the current study.
  • Exposure to more than 4 new chemical entities within 12 months before their first dose in the current study.
  • Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A participant's previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
  • Received a total body radiation dose of greater than 10.0 millisievert (mSv) (upper limit of world health organization [WHO] category II) or exposure to significant radiation (e.g., serial x-ray or computed tomography [CT] scans, barium meal, etc.) in the 3 years before this study.
  • Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • QTc >500 millisecond (msec). The QTc must be the QTcB.
  • 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 >21 units. One unit is equivalent to 8 g of alcohol: a glass (approximately 240 milliliter [mL]) of beer, 1 small glass (approximately 100 mL) of wine or 1 (approximately 25 mL) measure of spirits.
  • At screening, a supine blood pressure (BP) that is persistently higher than 140/90 millimeters of mercury (mmHg) taken in triplicate, unless deemed not clinically significant by the investigator.
  • At screening, a supine mean heart rate (HR) outside the range of 40-100 beats per minute, unless deemed not clinically significant by the investigator.
  • Has had an occupation which requires monitoring for radiation exposure, nuclear medicine procedures, or excessive x-rays within the past 12 months.
  • Unable to refrain from consumption of prohibited food and drinks from 7 days before the first dose of study medication until the follow up visit.
  • Participation in the study would result in donation of blood or blood products in excess of 550 mL within a 90 day period.
  • Unwillingness or inability to follow the procedures, including the use of the Entero-Test capsule.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products in the 6 months prior to screening.
  • History of drug abuse or dependence within 6 months of the study.
  • History of sensitivity to daprodustat, or their components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates their participation.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    London, NW10 7EW

Other trials in United Kingdom

About this study

Official title: An Open-label Study in Healthy Male Participants to Determine the Mass Balance, Absolute Bioavailability and Pharmacokinetics of Daprodustat, Administered as a Single Intravenous Microtracer (Concomitant With an Oral Dose of Non-radiolabelled Daprodustat) and a Single, Oral Radiolabelled Dose

Absorption, metabolism and excretion of daprodustat (GSK1278863) have been studied in previous clinical trials; however, the elimination routes and metabolic pathways of daprodustat have not been fully elucidated in humans. This is an open-label, single-center, non-randomized, 2-period, single-sequence, crossover, mass balance study in 6 healthy male participants. The aim of the study is to assess the excretion balance of daprodustat using [14C]-radiolabeled drug substance administered orally, and as an intravenous (IV) infusion, administered as a microtracer dose (concomitant with an oral, non-radiolabeled dose). Absolute bioavailability of an oral dose will also be assessed. Each participant will be involved in the study for up to 10 weeks which include a screening visit, two treatment periods (treatment periods 1 and 2), separated by about 7 days (at least 14 days between oral doses), and a follow up visit 1-2 weeks after the last assessment in treatment period 2. The primary objective of the study is to gain a better understanding of the compound's excretory and metabolic profile. This study will include sampling of duodenal bile to conduct qualitative assessment of drug metabolites in this matrix in order to characterize biliary elimination pathways.

Conditions
Anaemia
Being tested
[14C]-GSK1278863 solution for IV infusion, [14C]-GSK1278863 oral solution, Daprodustat 6 mg oral tablet
Keywords
GSK1278863, pharmacokinetics, mass balance, daprodustat
Medical subject headings
Anemia

What participants receive

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

  • [14C]-GSK1278863 solution for IV infusionDrug

    It is a clear, colorless solution free from visible particulate matter. Participants will receive 10 mL of 5 µg/mL of [14C]-GSK1278863 IV solution (total dose: 50 µg) by IV infusion over 1 hour.

  • [14C]-GSK1278863 oral solutionDrug

    It is a clear, colorless solution. Participants will receive 125 mL of 200 µg/mL of [14C]-GSK1278863 oral solution (total dose: 25 mg).

  • Daprodustat 6 mg oral tabletDrug

    It is a 9.0 millimeter (mm) round, white film coated tablet.

Study groups in NCT03239522
Study groupRoleWhat they receive
All participants receiving treatmentExperimentalEach participant will receive a single 6 milligram (mg) oral dose of daprodustat on Day 1 of period 1. After approximately 1 hour, participants will receive 50 microgram (µg) of [14C]-GSK1278863 by IV infusion over 1 hour. On Day 1 of period 2, each participant will receive 25 mg [14C]-GSK1278863 as an oral solution.
Receives: Drug: [14C]-GSK1278863 solution for IV infusion; Drug: [14C]-GSK1278863 oral solution; Drug: Daprodustat 6 mg oral tablet

What is being measured

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

  1. Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-Inf]) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863

    Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  2. AUC (0-Inf) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863

    Blood samples were planned to be collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error. Data were not analyzed for radiolabeled oral dose of GSK1278863 as there were not enough data points captured for a terminal slope required to calculate AUC (0-inf). The blood assay could not detect radiation levels at the time points blood was drawn to go into these calculations.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  3. AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC [0-t]) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863

    Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  4. AUC (0-t) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863

    Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  5. Maximum Observed Plasma Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863

    Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  6. Cmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863

    Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  7. Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863

    Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  8. Tmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863

    Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  9. Apparent Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863

    Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  10. T1/2 of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863

    Blood samples were planned to be collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error. Data were not analyzed for radiolabeled oral dose of GSK1278863 as there were not enough data points captured for a terminal slope required to calculate t1/2. The blood assay could not detect radiation levels at the time points blood was drawn to go into these calculations.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  11. Volume of Distribution at Steady State (Vss) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863

    Plasma samples were collected from participants at indicated time points in treatment period 1, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  12. Vss of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863

    Blood samples were planned to be collected from participants at indicated time points in treatment period 1, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  13. Total Systemic Clearance (CL) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863

    Plasma samples were collected from participants at indicated time points in treatment period 1 after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  14. CL of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863

    Blood samples were planned to be collected from participants at indicated time points in treatment period 1 after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  15. Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863

    Urine samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in urine. All participants were asked to void their bladders before study treatment administration.

    Measured: Pre-dose and then over 24 hours collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120,120-144 and 144-168 hours post-dose in treatment period 2

  16. Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863

    Fecal samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in feces.

    Measured: Pre-dose and then over 24 hour collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post-dose in treatment period 2

  17. Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time

    Urine and fecal samples were collected at the indicated time points to determine the rate and extent of cumulative excretion of total radioactivity in urine and feces.

    Measured: Pre-dose and then over 24 hour collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post-dose in treatment period 2

Secondary outcomes (29)

  1. AUC (0-Inf) of GSK1278863 in Plasma Following Administration IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  2. AUC(0-t) of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  3. Cmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  4. Tmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  5. T1/2 of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  6. AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863.Pharmacokinetic analysis was conducted using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  7. AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  8. Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  9. Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  10. T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses

    Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2

  11. Vss of GSK1278863 in Plasma Following IV Dose Administration

    Plasma samples were collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  12. Vss of GSK1278863 Metabolites in Plasma Following IV Dose Administration

    Plasma samples were planned to be collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  13. CL of GSK1278863 in Plasma Following IV Dose Administration

    Plasma samples were collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  14. CL of GSK1278863 Metabolites in Plasma Following IV Dose Administration

    Plasma samples were planned to be collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  15. Absolute Bioavailability of GSK1278863 Following Oral Dosing

    Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(oral)/Dose(oral) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses administered in treatment period 1 was analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters.

    Measured: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1

  16. Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg

    Blood samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of [14C]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220) and M33 combined, M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. 2 pooled plasma samples were prepared. Aliquots of plasma samples collected between 0 to 8 hours post-dose from each participant were pooled in proportion to the time intervals. An equal amount of the individual pools from each participant was then pooled to create 1 plasma sample that was representative of the mean area under curve over the range of 0-8 hour. The second pool (10-12 hours pool) was obtained by mixing equal volume of the plasma samples at 10 and 12 hour across all participants. Percent radioactivity recovered for each metabolite in plasma following a single oral dose of [14C]-GSK1278863 at 25 mg is presented.

    Measured: 0-8 hours, 10-12 hours in period 2

  17. Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg

    Urine samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of [14C]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220) and M33 combined, M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. One pooled urine sample was prepared by urine collected from 0 to 24 hours post dose from all participants. Percent radioactivity recovered for each metabolite in urine following a single oral dose of [14C]-GSK1278863 at 25 mg is presented.

    Measured: 0-24 hours in period 2

  18. Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg

    Feces samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of [14C]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220), M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. One pooled feces sample was prepared by samples collected from 0 to 120 hours post dose from all participants. Percent radioactivity recovered for each metabolite in feces following a single oral dose of [14C]-GSK1278863 at 25 mg is presented.

    Measured: 0-120 hours in period 2

  19. Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion

    The bile string was swallowed by participants prior to oral dose and was removed 3 hours after the oral dose (1 hour after the end of the IV infusion) in treatment period-1. Duodenal bile string extracts were pooled to create a single pool sample to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single dose of [14C]-GSK1278863 50 µg IV infusion. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220), M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102). Mean percent radioactivity recovered for each metabolite in bile following a single dose of [14C]-GSK1278863 50 µg IV infusion is presented.

    Measured: 3 hours post-oral dose in period 1

  20. Number of Participants With Adverse Events (AEs) and Serious AEs (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 which 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, associated with liver injury and impaired liver function or any other situations as per Medical or scientific judgment. Safety Population comprised of all participants who take at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.

    Measured: Up to 43 days

  21. Number of Participants With AEs at a Particular Severity

    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. Severity was categorized as mild, moderate and severe. The number of participants with AEs at any type of severity (mild, moderate and severe) has been presented.

    Measured: Up to 43 days

  22. Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range

    Blood samples were collected from participants at indicated time points for the analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Alkaline phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Potassium, Protein, Sodium and Urea. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (example given [e.g.], High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 43 days

  23. Number of Participants With Worst Case Hematology Results Relative to Normal Range

    Blood samples were collected from participants at indicated time points for the analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes, and Reticulocytes/Erythrocytes. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 43 days

  24. Number of Participants With Abnormal Urinalysis Findings

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including specific gravity and PH of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase in urine.

    Measured: Up to 43 days

  25. Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Full 12-lead ECGs were recorded with the participant in a supine position. The number of participants with abnormal ECG findings at indicated time points were presented. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.

    Measured: Pre-dose (on Day 1) and Day 8 in treatment period 2; 144 hours (Day 7) in treatment period 1

  26. Change From Baseline in Blood Pressure

    Vital sign including systolic and diastolic blood pressure were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the mean of the 3 pre-dose measurements (Average [Avg] Pre-dose) taken on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.

    Measured: Baseline (average of Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2

  27. Change From Baseline in Heart Rate

    Heart rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the mean of the 3 pre-dose measurements (Avg Pre-dose) taken on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.

    Measured: Baseline (average of Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2

  28. Change From Baseline in Respiratory Rate

    Respiratory rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the pre-dose on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.

    Measured: Baseline (Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2

  29. Change From Baseline in Body Temperature

    Body temperature measurement was performed in participants at indicated time points. Baseline is defined as the pre-dose on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.

    Measured: Baseline (Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2

Timeline

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

  1. First posted4 Aug 2017
  2. Study start10 Oct 2017
  3. Primary completion28 Nov 2017
  4. Study completion28 Nov 2017

Resources

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
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03239522
Sponsor's protocol ID
200232
Other IDs
2017-001729-42, 2017
Status last verified
Nov 2019
First submitted
17 Jul 2017
Last updated
3 Dec 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [14C]-GSK1278863 solution for IV infusion, [14C]-GSK1278863 oral solution and Daprodustat 6 mg oral tablet in people with Anaemia, run by GlaxoSmithKline at 1 site in United Kingdom.

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 9 inclusion and 32 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 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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 18 Mar 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?

Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-Inf]) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 (time frame: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2). The study lists 17 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 NCT03239522.

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 3 Dec 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in