A 4-Week, Phase II, Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled, Parallel-Group, Multi-Center Study to Evaluate the Safety, Efficacy and Pharmacokinetics of GSK1278863 in Japanese Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease
Study to Evaluate the Safety, Efficacy and Pharmacokinetics of GSK1278863 in Japanese Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease
Sponsors
Source
GlaxoSmithKline
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
This study aims to characterize the relationship between dose of GSK1278863 and hemoglobin
(Hgb) response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic
kidney disease (CKD). It is anticipated that the data generated will enable selection of the
starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials. This
study will consist of a screening phase of 3-9 weeks, a 4-week treatment phase and a
follow-up visit approximately 4 weeks after completing treatment.
Overall Status
Completed
Start Date
2013-11-05
Completion Date
2014-08-06
Primary Completion Date
2014-08-06
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Change From Baseline (CFB) in Hemaglobin (Hgb) at Week 4 |
Baseline (Day 1) and Week 4 |
Secondary Outcome
Measure |
Time Frame |
CFB in Hgb Upto Week 8 |
Baseline (Day 1) Upto Week 8 |
Number of Participants Who Achieved Hgb Response at Week 4 |
Week 4 |
Percentage of Participants Who Achieved Hgb Response at Week 4 |
Week 4 |
Number of Participants Who Reached Pre-defined Hgb Stopping Criteria |
Upto Week 4 |
Maximum Observed CFB in Erythropoietin (EPO) Upto Week 4 |
Baseline (Day 1) Upto Week 4 |
Maximum Observed Percent CFB in Peak Vascular Endothelial Growth Factor (VEGF) Upto Week 4 |
Baseline (Day 1) Upto Week 4 |
Percent CFB in Hepcidine Upto Week 4 |
Baseline (Day 1) Upto Week 4 |
CFB in Ferritin at Week 4 |
Baseline (Day 1) and Week 4 |
CFB in Total Iron Binding Capacity [TIBC], Unbound Iron Binding Capacity [UIBC] and Iron at Week 4 |
Baseline (Day 1) and Week 4 |
CFB in Transferrin at Week 4 |
Baseline (Day 1) and Week 4 |
Percent CFB in Transferrin Saturation (TS) at Week 4 |
Baseline (Day 1) and Week 4 |
Plasma Pharmacokinetic Concentration of GSK1278863 and Metabolites (M) at Week 4 |
Week 4 |
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) on Therapy |
Upto Week 4 |
Number of Participants With Chemistry and Hematology Data of Potential Clinical Importance (PCI) Upto Week 4 |
Upto Week 4 |
Number of Participants With Vital Signs Parameters Systolic and Diastolic Blood Pressure (SBP,DBP) of PCI Upto Week 4 |
Upto Week 4 |
Number of Participants With Vital Sign Parameter Heart Rate (HR) of PCI Upto Week 4 |
Upto Week 4 |
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Upto Week 4 |
Upto Week 4 |
Enrollment
97
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
GSK1278863 will be supplied as film coated tablets for oral administration containing 1 mg, 2 mg, or 5 mg of GSK1278863.
Arm Group Label
GSK1278863 6 mg
GSK1278863 4 milligrams (mg)
GSK1278863 8 mg
GSK1278863 10 mg
Intervention Type
Drug
Intervention Name
Description
Film coated tablets of GSK1278863 matching placebo for oral administration.
Arm Group Label
Placebo
Eligibility
Criteria
Inclusion Criteria:
- Age (Informed concent): Japanese >=20 years of age
- Gender (Screening 2 verification only): Female and male
- Females: must be of childbearing potential, and must agree to use one of the approved
contraception methods from Screening 2 until completion of the Follow-up Visit. OR Of
non-childbearing potential defined as pre-menopausal females with a documented tubal
ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous
amenorrea [in questionable cases a blood sample with simultaneous follicle stimulating
hormone 23.0 - 116.3 million international units (MIU)/millilitre (mL) and estradiol
<= 10 picograms (pg)/mL is confirmatory]. Females on hormone replacement therapy (HRT)
whose menopausal status is in doubt will be required to use one of the approved
contraception methods if they wish to continue their HRT during the study. Otherwise
they must discontinue HRT to allow confirmation of post-menopausal status prior to
study enrolment. For most forms of HRT, at least 2 weeks will elapse between the
cessation of therapy and the blood draw; this interval depends on the type and dosage
of HRT. Following confirmation of their post-menopausal status, they can resume use of
HRT during the study without use of a contraceptive method. Males: must agree to use
one of the approved contraceptive methods from the time of Screening 2 until
completion of the Follow-up Visit.
- Corrected QT interval (QTc) (Screening 2 verification only): Bazett's Correction of QT
Interval (QTcB) <470 milliseconds (msec) or QTcB <480 msec in subjects with bundle
branch block. There is no QTc inclusion criterion for a subject with a predominantly
paced rhythm.
- Dialysis frequency: On hemodialysis (HD) three times weekly for at least 8 weeks prior
to Screening 2 through Day 1.
- Dialysis adequacy (Screening 2 only): A single-pool Kt/Vurea of 1.2 based on a
historical value obtained within the prior month 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%.
- Hemoglobin: Target stable Hgb between 9.5-12.0 g/dL at screening.
- Stable erythropoiesis-stimulating agent (ESA) dose (Screening 2 only): Using the same
ESA (epoetins or their biosimilar, or darbepoietin) with total weekly doses that
varied by no more than 50% during the 4 weeks prior to Screening 2.
- Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous
(IV) (<100 milligrams [mg]/week) iron supplementation. If subjects are on oral or IV
iron, then doses must be stable for the 4 weeks prior to Screening 2, and Screening 2
through Week 4.
Exclusion Criteria:
- Dialysis modality: Planned change from HD to peritoneal dialysis within the study time
period.
- Renal transplant: Renal transplant anticipated or scheduled within the study time
period.
- High ESA dose (Screening 2 verification only): As defined by an epoetin dose of >=360
IU/kilograms (kg)/week IV or darbepoetin dose of >=1.8 micrograms (μg)/kg/week IV
within the prior 8 weeks through Screening 2.
- methoxy polyethylene glycol epoetin beta (Screening 2 verification only): Use of
methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Screening 2.
- Vitamin B12: At or below the lower limit of the reference range
- Folate: <2.0 nanograms (ng)/mL (<4.5 nanomoles [nmol]/liters [L])
- Iron status: Ferritine <100 ng/mL (<100 μg/L) AND Transferrin saturation (TSAT) <20%
- Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to
Screening 2 through Day 1.
- Stroke or transient ischemic attack: Within the 8 weeks prior to Screening 2 through
Day 1.
- Heart failure: Class III/IV heart failure, as defined by the New York Heart
Association (NYHA) functional classification system or symptomatic right heart failure
diagnosed prior to Screening 2 through Day 1.
- Hypertension: Defined using pre-dialysis vitals of diastolic blood pressure >100 mmHg
or systolic blood pressure >170 mmHg.
- Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as
deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset
or worsening limb ischemia requiring intervention), except vascular access thrombosis,
within the 8 weeks prior to Screening 2 through Day 1
- Eyes: History of proliferative retinopathy requiring treatment within the prior 12
months or macular edema requiring treatment..
- Inflammatory disease: Active chronic inflammatory disease that could impact
erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis,
celiac disease) diagnosed prior to Screening 2 through Day 1.
- 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 other than renal disease diagnosed prior to Screening 2 through Day 1.
- 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) >2.0 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN]; or other
hepatic abnormalities that in the opinion of the investigator (subinvestigator) would
preclude the subject from participation in the study.
- Major surgery: Major surgery (excluding vascular access surgery) within the prior 8
weeks, within the Screening 2 to Day 1 or planned during the study.
- Transfusion: Blood transfusion within the prior 8 weeks, within the Screening 2 to Day
1 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 2 through Day 1.
- Acute infection: Clinical evidence of acute infection or history of infection
requiring IV antibiotic therapy within 8 weeks prior to Screening 2 through Day 1.
- Malignancy: Subjects with a history of malignancy within the prior 5 years, who
receiving treatment for cancer, or who have a strong family history of cancer (e.g.,
familial cancer disorders); with the exception of squamous cell or basal cell
carcinoma of the skin that has been definitively treated prior to Screening 2 through
Day 1.
- 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 from Screening 2 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 2 through Day 1.
- Pregnancy or lactation: Pregnant females as determined by positive serum Human
Chorionic Gonadotrophin (hCG) test (Screening 2 only) OR women who are lactating at
Screening 2 and/or Day 1 or during the trial.
- Other conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the Investigator would consider inappropriate to participate
in the study.
Gender
All
Minimum Age
20 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
GSK Clinical Trials |
Study Director |
GlaxoSmithKline |
Location
Facility |
GSK Investigational Site Aichi 446-0053 Japan |
GSK Investigational Site Aichi 446-0065 Japan |
GSK Investigational Site Aichi 454-0932 Japan |
GSK Investigational Site Aichi 455-0021 Japan |
GSK Investigational Site Aichi 465-0025 Japan |
GSK Investigational Site Aichi 470-1201 Japan |
GSK Investigational Site Chiba 276-0031 Japan |
GSK Investigational Site Fukuoka 804-0094 Japan |
GSK Investigational Site Ibaraki 300-0835 Japan |
GSK Investigational Site Ibaraki 305-0861 Japan |
GSK Investigational Site Ibaraki 310-0844 Japan |
GSK Investigational Site Kagawa 761-8024 Japan |
GSK Investigational Site Kanagawa 216-0007 Japan |
GSK Investigational Site Miyagi 981-0911 Japan |
GSK Investigational Site Nagano 390-0821 Japan |
GSK Investigational Site Nagano 390-1401 Japan |
GSK Investigational Site Niigata 950-2038 Japan |
GSK Investigational Site Osaka 543-0052 Japan |
GSK Investigational Site Osaka 547-0024 Japan |
GSK Investigational Site Tokyo 158-0094 Japan |
GSK Investigational Site Toyama 930-0964 Japan |
Location Countries
Country
Japan
Verification Date
2018-02-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
5
Intervention Browse
Mesh Term
Glycine
Arm Group
Arm Group Label
GSK1278863 4 milligrams (mg)
Arm Group Type
Experimental
Description
Subjects will receive GSK1278863 4 mg once daily for 4 weeks
Arm Group Label
GSK1278863 6 mg
Arm Group Type
Experimental
Description
Subjects will receive GSK1278863 6 mg once daily for 4 weeks
Arm Group Label
GSK1278863 8 mg
Arm Group Type
Experimental
Description
Subjects will receive GSK1278863 8 mg once daily for 4 weeks
Arm Group Label
GSK1278863 10 mg
Arm Group Type
Experimental
Description
Subjects will receive GSK1278863 10 mg once daily for 4 weeks
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
Subjects will receive placebo once daily for 4 weeks
Firstreceived Results Date
N/A
Patient Data
Sharing Ipd
Yes
Ipd Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study Docs
Study Doc
Doc Id
116099
Doc Type
Clinical Study Report
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Statistical Analysis Plan
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Informed Consent Form
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Dataset Specification
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Individual Participant Data Set
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Study Protocol
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Doc Id
116099
Doc Type
Annotated Case Report Form
Doc Url
https://www.clinicalstudydatarequest.com
Doc Comment
For additional information about this study please refer to the GSK Clinical Study Register
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Study First Submitted
October 31, 2013
Study First Submitted Qc
December 19, 2013
Study First Posted
December 24, 2013
Last Update Submitted
February 9, 2018
Last Update Submitted Qc
February 9, 2018
Last Update Posted
February 12, 2018
Results First Submitted
April 26, 2017
Results First Submitted Qc
February 9, 2018
Results First Posted
February 12, 2018
ClinicalTrials.gov processed this data on December 12, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.