Oral Iron Absorption Study



Status:Not yet recruiting
Conditions:Anemia
Therapuetic Areas:Hematology
Healthy:No
Age Range:18 - Any
Updated:1/12/2019
Start Date:February 15, 2019
End Date:September 6, 2019
Contact:US GSK Clinical Trials Call Center
Email:GSKClinicalSupportHD@gsk.com
Phone:877-379-3718

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A Repeat Dose, Open Label, Two Period, Randomized, Cross Over Study to Compare the Effect of Daprodustat to Recombinant, Human Erythropoietin (rhEPO) on Oral Iron Absorption in Adult Participants With Anemia Associated With Chronic Kidney Disease Who Are Not on Dialysis

Daprodustat administration has the potential, by virtue of increasing hypoxia-inducible
factor (HIF) levels, to increase oral iron absorption and incorporation into hemoglobin
(Hgb). Therefore, the purpose of this study is to compare the effect of daprodustat to rhEPO
(i.e., epoetin alfa or darbepoetin alfa) on non-heme oral iron absorption using stable
isotopic iron (57Fe and 58Fe) by measuring incorporation of iron in erythrocytes. This study
will be a randomized, repeat dose, open label, two period cross-over study in adult, male and
female subjects with anemia associated with chronic kidney disease who are not on dialysis
currently treated with stable doses (<=50% change in 4-weekly dose) for at least 8 weeks
prior to and including the screening period, of rhEPO (i.e., epoetin alfa or darbepoetin
alfa). Sufficient subjects will be enrolled such that at least 12 subjects comprise the
Evaluable Population. The study will compare the fractional iron absorption between treatment
arms (daprodustat and rhEPO [i.e., epoetin alfa or darbepoetin alfa]) and will evaluate the
difference is equal/not equal to zero. Approximate duration of study participation will be up
to 73 days.


Inclusion Criteria:

- Subject must be at least 18 years of age inclusive, at the time of signing the
informed consent.

- Subjects who are Stage 3, 4 or 5 Chronic kidney disease (CKD) (confirmed at Week-4
only) defined by estimated glomerular filtration rate (eGFR) using the CKD
Epidemiology Collaboration (CKD-EPI) formula.

- Subjects who are currently treated with stable doses (<=50% change in 4-weekly dose)
for at least 8 weeks prior to and including the screening period, of rhEPO (i.e.,
epoetin alfa or darbepoetin alfa).

- Subjects with Hgb levels between 9.0 and 11.5 grams per deciliter (g/dL), inclusive,
who meet the Hgb stability criteria.

- Subjects may be on stable maintenance oral iron supplementation. If subjects have been
on intravenous (IV) iron, then subjects will not have received IV iron for 8 weeks
prior to the Day 1 visit.

- Male or Female subjects may participate. A female subject is eligible to participate
if she is not pregnant, not breastfeeding, and at least one of the following
conditions applies: not a woman of childbearing potential (WOCBP), or a WOCBP who
agrees to follow the contraceptive guidance during the treatment period to the
follow-up visit.

- Capable of giving signed informed consent

Exclusion Criteria:

- On dialysis or clinical evidence of impending need to initiate dialysis within 90 days
after study start (i.e., Day 1).

- Planned kidney transplant within 3 months after study start.

- A positive test for Human Immunodeficiency Virus (HIV) antibody.

- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients
in the investigational products

- Use of any prescription or non-prescription drugs or dietary supplements that are
prohibited from screening until the end of Treatment Period 2.

- Planned or current administration of methoxy polyethylene glycol (PEG)-epoetin beta.

- The subject has participated in a clinical trial and has received an experimental
investigational product within the prior 30 days or 5 half lives, whichever is longer,
from screening through Day 1.

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

- Ferritin outside the range between 100 and 500 nanogram per milliliter (ng/mL),
inclusive, at screening.

- Transferrin saturation (TSAT) outside the range between 15% and 40%, inclusive, at
Screening.

- Folate < 2.0 ng/mL (4.5 nanomoles per liter [nmol/L]; may rescreen in a minimum of 8
weeks) at screening.

- Hepcidin > 150 ng/mL at screening.

- High sensitivity C-reactive protein (hsCRP) >=20 microgram per milliliter (μg/mL) at
screening.

- Myocardial infarction or acute coronary syndrome: <=8 weeks prior to screening through
Day 1.

- Hospitalization for greater than 24 hours: <=8 weeks prior to screening through Day 1

- Stroke or transient ischemic attack <=8 weeks prior to screening through Day 1.

- Class IV heart failure, as defined by the New York Heart Association (NYHA) functional
classification system.

- Resting systolic blood pressure >160 millimeter of mercury (mmHg) or diastolic blood
pressure >100 mmHg at screening.

- QT interval corrected for heart rate using Bazett's formula (QTcB): QTcB >500
milliseconds (msec), or QTcB > 530 msec in subjects with Bundle Branch Block. There is
no corrected QT interval (QTc) exclusion for subjects with a predominantly paced
rhythm.

- Active chronic inflammatory disease that could impact erythropoiesis.

- History of bone marrow aplasia or pure red cell aplasia.

- Conditions, other than anemia associated with chronic kidney disease, which can affect
erythropoiesis.

- Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR
clinically significant gastrointestinal (GI) bleeding from <=4 weeks prior to
screening through Day 1.

- Liver disease (any of the following): Alanine transaminase (ALT) >2 times upper limit
of normal (ULN; screening only); Bilirubin >1.5 times ULN (screening only). Isolated
bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%; Current or chronic history of liver disease, or known hepatic or
biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).

- Major surgery (excluding vascular access surgery) within the 8 weeks prior to
screening through Day 1, or planned during the study.

- Blood transfusion within 8 weeks prior to screening through Day 1, or an anticipated
need for blood transfusion during the study.

- Clinical evidence of an acute infection, or history of infection requiring IV
antibiotic therapy from 4 weeks prior to screening through Day 1. Prophylactic
antibiotics are allowed.

- History of malignancy within the two years prior to screening through Day 1 or
currently receiving treatment for cancer, with the exception of localized squamous
cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to Day 1.

- 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.

Hgb Stability Criteria:

- Entry into the study requires a stable Hgb between 9.0 - 11.5 g/dL.

- This criterion is assessed from an average of three Hgb values obtained via a
validated point-of-care device to measure Hgb on site during the screening period at
Week -4, Week -2 and on Day 1.

- The Hgb stability assessment is the difference between the maximum and minimum values
of the three Hgb measurements obtained between Week -4 and Day 1.
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