Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent



Status:Completed
Conditions:Renal Impairment / Chronic Kidney Disease, Anemia
Therapuetic Areas:Hematology, Nephrology / Urology
Healthy:No
Age Range:18 - Any
Updated:5/23/2018
Start Date:February 17, 2016
End Date:January 25, 2017

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A 29-day, Randomized, Double-blinded, Placebo-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

GSK1278863 is an orally available, hypoxia-inducible factor - prolyl hydroxylase inhibitor,
currently being investigated as a treatment for anemia associated with chronic kidney
disease. GSK1278863 has been given as a once daily regimen in clinical studies to date.
However, physicians in countries that use a three-times weekly hemodialysis schedule prefer
to give the anemia medicine at the same time as the dialysis session. This study will test
how well GSK1278863 can maintain hemoglobin levels when given three-times weekly, for 29
days.

This study will describe the relationship between hemoglobin and GSK1278863 given three-times
weekly. The data from this study will allow for conversion of once daily doses to three-times
weekly doses.


Inclusion Criteria:

- More than or equal to 18 years of age, at the time of signing the informed consent.

- Hemoglobin: Stable Hemoglobin 9.0 - 11.5 gram per deciliter (g/dL).

- Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three to
five times weekly for at least 4 weeks prior to Day -28 Screening through Day 29.

- Dialysis adequacy: A single pool Kt/Vurea of >=1.2 based on a historical value
obtained within the prior three months in order to ensure the adequacy of dialysis. If
Kt/Vurea is not available, then an average of the last 2 values of urea reduction
ratio (URR) of at least 65 percent. NOTE: Only needs confirming at Day -28.

- Erythropoiesis-stimulating agent (ESA)dose: Treated with the same ESA (epoetins or
their biosimilars, or darbepoetin or methoxy polyethylene glycol [PEG]-epoetin beta)
with total weekly dose varying by no more than 50 percent during the 4 weeks prior to
Day -28.

- Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous
(IV) (<=100 milligram (mg)/week) iron supplementation. If subjects are on oral or IV
iron, then doses must be stable for the 4 weeks prior to Day -28, during the screening
phase, and through the 29 days of treatment.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and in study protocol.

Exclusion Criteria:

- Dialysis modality: Planned change from HD to peritoneal dialysis within the study time
period.

- Renal transplant: Planned for living-related kidney transplant.

- High ESA dose: An epoetin dose of >=360 international unit (IU)/kilogram (kg)/week IV
or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram
(mcg)/kg/week IV or SC or methoxy PEG-epoetin beta dose of >= 2.2 mcg/kg/week within
the prior 8 weeks through Day 1 (randomization).

- Administration of methoxy PEG-epoetin beta within the prior 4 weeks through Day 1
(randomization).

- Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to
Screening through Day 1 (randomization).

- Stroke or transient ischemic attack: Within 8 weeks prior to Screening though Day 1
(randomization).

- Heart failure: Class IV heart failure, as defined by the New York Heart Association
(NYHA) functional classification system diagnosed prior to Screening through Day 1
(randomization).

- Correction of Q-T Interval using Bazett's formula (QTcB): QTcB >500 millisecond (msec)
or QTcB >530 msec in subjects with Bundle Branch Block. There is no correction of Q-T
Interval (QTc) exclusion for subjects with a predominantly paced rhythm.

- Inflammatory disease: Active chronic inflammatory disease that could impact
erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis,
celiac disease) diagnosed prior to Screening through Day 1 (randomization).

- Hematological disease: Any hematological disease including those affecting platelets,
white or red blood cells (e.g., sickle cell anemia, myelodysplastic syndromes,
hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation
disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other
cause of anemia of chronic disease other than renal disease diagnosed prior to
Screening though Day 1 (randomization).

- Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening
of abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase
(AST) >2x upper limit of normal (ULN) or total bilirubin >1.5xULN]; or other hepatic
abnormalities that in the opinion of the investigator would preclude the subject from
participating in the study.

NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not
met.

- Major surgery: Major surgery (excluding vascular access surgery) within the 8 weeks
prior to Screening, during the Screening phase, or planned during the study.

- Transfusion: Blood transfusion within the 8 weeks prior to Screening, during the
Screening phase or an anticipated need for blood transfusion during the study.

- Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or
esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks
prior to Screening through Day 1 (randomization).

- Acute Infection: Clinical evidence of acute infection or history of infection
requiring IV antibiotic therapy within the 4 weeks prior to Screening through Day 1
(randomization). NOTE: IV antibiotics as prophylaxis are allowed.

- Malignancy: History of malignancy within the two years prior to randomization or
currently receiving treatment for cancer, or has a known >=4 centimeter complex kidney
cyst (i.e. Bosniak Category II F, III of IV). NOTE: ONLY exception is squamous cell or
basal cell carcinoma of the skin that has been definitively treated >=8 weeks prior to
Screening.

- Severe allergic reactions: History of severe allergic or anaphylactic reactions or
hypersensitivity to excipients in the investigational product

- Drugs and supplements: Use of any prescription or non-prescription drugs or dietary
supplements that are prohibited (as per protocol) from Screening until the Follow-up
Visit.

- Prior investigational product exposure: The Subject has participated in a clinical
trial and has received an experimental investigational product within the prior 30
days from Screening through Day 1 (randomization).

- Other conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the investigator considers would put the subject at
unacceptable risk, which may affect study compliance or prevent understanding of the
aims or investigational procedures or possible consequences of the study.

- Females ONLY: A female subject is not eligible to participate if she is pregnant [as
confirmed by a positive serum human chorionic gonadotrophin (hCG) test for females of
reproductive potential (FRP) only], breastfeeding, and if of reproductive potential
does not agree to follow one of the options listed in the GSK Modified List of Highly
Effective Methods for Avoiding Pregnancy in FRP.

- Vitamin B12: At or below the lower limit of the reference range (may rescreen in a
minimum of 8 weeks).

- Folate: <2.0 nanogram (ng) per millilitre (mL) (4.5 nanomole/liter [L]) (may rescreen
in a minimum of 4 weeks).

- Ferritin: <100 ng/mL (<100 mcg/L).

- Transferrin saturation (TSAT): <20 percent.
We found this trial at
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Portsmouth, New Hampshire 03802
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Bronx, New York 10461
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Calgary, Alberta
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Escondido, California 92025
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Kalamazoo, Michigan 49007
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Kansas City, Missouri 64128
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Northridge, California 91325
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Pembroke Pines, Florida 33028
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Pontiac, Michigan 48341
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Roseville, Michigan 48066
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San Dimas, California 91773
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Wichita, Kansas 67207
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