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Study of GSK1278863 to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01920594
First Posted: August 12, 2013
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
August 8, 2013
August 12, 2013
September 18, 2017
December 7, 2017
December 7, 2017
October 31, 2013
October 8, 2014   (Final data collection date for primary outcome measure)
  • Change From Baseline to Peak in Cerebrospinal Fluid (CSF) S100 Beta Within 48 Hours Following Descending Thoracic Aorta/Thoracoabdominal Aortic Aneurysm (DTA/TAAA) Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    S100 beta is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF S100 beta. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
  • Change From Baseline to Peak in CSF Glial Fibrillary Acidic Protein (GFAP) Within 48 Hours Following DTA/TAAA Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    GFAP is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples for the analysis of GFAP was collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF GFAP. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Change from baseline to peak in cerebor spinal fluid (CSF) S100beta and Glial fibrillary acidic protein (GFAP) within 48 hours following DTA/TAAA repair [ Time Frame: Baseline, Day 0, Day 1, Day 2 ]
To assess the effect of prophylactic GSK1278863 versus placebo on CSF markers (S100beta and GFAP) of central nervous system (CNS) injury. Samples of approximately 5mL of CSF will be obtained directly from the lumbar drain
Complete list of historical versions of study NCT01920594 on ClinicalTrials.gov Archive Site
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Follow-up (Day 45) ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, considered to be medically significant or is associated with liver injury and impaired liver function.
  • Number of Participants With Vital Signs of Potential Clinical Importance (PCI) [ Time Frame: Up to Follow-up (Day 45) ]
    Vital sign measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate. Criteria for vital sign values meeting PCI included: SBP < 70 millimeters of mercury (mmHg) and > 160 mmHg; DBP < 45 mmHg and > 110 mmHg. Data for participants with vital signs values outside the potential clinical importance range has been presented. Only those parameters for which at least one value of PCI was reported are summarized.
  • Number of Participants With Abnormal Electrocardiography (ECG) Parameters [ Time Frame: Up to Follow-up (Day 45) ]
    Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate intervals. Data for participants with abnormal-clinical significant (CS) and abnormal-not clinically significant (NCS) ECG findings on post-operative Days 1, 2, 3, 4, 5, 6, 7 and during Follow-up Visits has been presented.
  • Number of Participants With Clinical Chemistry Parameters of PCI [ Time Frame: Up to post-operative Day 7 ]
    Blood samples for assessment of clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, blood urea nitrogen (BUN), creatinine, glucose, sodium, creatine phosphokinase, potassium, chloride, total carbon dioxide, calcium, total and direct bilirubin, uric acid, albumin and total protein was done at Randomization, Day 0 (done prior to 100 mg on-call dosing), 1, 2, 3, 4, 5, 6 and 7. Only those parameters for which at least one value of PCI was reported are summarized. Data for participants with clinical chemistry values outside the PCI range has been presented.
  • Number of Participants With Hematology Parameters of PCI [ Time Frame: Up to post-operative Day 7 ]
    Blood samples for assessment of hematology parameters platelet count, red blood cell count, white blood cell count, reticulocyte count, hemoglobin, hematocrit, mean corpuscle volume, mean corpuscle hemoglobin, mean corpuscle hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils and basophils was done at Randomization, Day 0 (done prior to 100 mg on-call dosing), 1, 2, 3, 4, 5, 6 and 7. Only those parameters for which at least one value of PCI was reported are summarized. Data for participants with hematology values outside the PCI range has been presented.
  • Change From Baseline in Area Under Curve (AUC) for CSF S100 Beta to 48 Hours [ Time Frame: Baseline(Day 0) to 48 hours following DTA/TAAA repair ]
    S100 beta was a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. AUC for CSF S100 beta from Baseline to 48 hours following DTA/TAAA repair was assessed to measure central nervous system injury. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
  • Change From Baseline in AUC for CSF GFAP to 48 Hours [ Time Frame: Baseline(Day 0) to 48 hours following DTA/TAAA repair ]
    GFAP was a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. AUC for CSF GFAP from Baseline to 48 hours following DTA/TAAA repair was assessed to measure central nervous system injury. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
  • Change From Baseline to Peak in CSF Biomarker Erythropoietin Within 48 Hours Following DTA/TAAA Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    CSF biomarker erythropoietin samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF erythropoietin. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
  • Change From Baseline to Peak in CSF Biomarker Lactate Dehydrogenase Within 48 Hours Following DTA/TAAA Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    CSF biomarker lactate dehydrogenase samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF lactate dehydrogenase. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
  • Change From Baseline to Peak in CSF Biomarker Tau Protein Within 48 Hours Following DTA/TAAA Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    CSF biomarker tau protein samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF tau protein. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
  • Change From Baseline to Peak in CSF Biomarker Neuron-specific Enolase (NSE) Within 48 Hours Following DTA/TAAA Repair [ Time Frame: Baseline (Day 0) to 48 hours following DTA/TAAA repair ]
    CSF biomarker NSE samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF NSE. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
  • Number of Participants With Neurologic Outcomes Assessed by the National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45) ]
    The NIHSS was a systematic assessment tool that provided a quantitative measure of stroke-related neurologic deficit. A trained observer rates the participant's ability to answer questions and perform activities. Ratings for each item are scored with 0 as normal, and there was an allowance for untestable items. The NIHSS scores were categorized as: No event (NIHSS score=0), Mild (NIHSS score 1-4), Moderate (NIHSS score 5-15), or Severe (NIHSS score >15). The single participant assessment required less than 10 minutes to complete. Data for participants with NIHSS administrated at surgical day, post-operative Day 1, Day 2, Day 7 and Follow-up Visit has been reported.
  • Number of Participants With Neurologic Outcomes Assessed by Modified Rankin Scale (mRS) [ Time Frame: Post-operative Day 7 and follow-up (Day 45) ]
    The mRS was a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS was a 6 point disability scale with possible scores ranging from 0 up to 5. A separate category (of 6) was added for participants who died. The mRS scores were categorized as mild (mRS score 0-1), moderate (mRS score 2-3), or severe (mRS score >=4).
  • Number of Participants With Neurologic Outcomes Assessed by the American Spinal Injury Association (ASIA) Lower Extremity Motor Outcome Scale [ Time Frame: Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45) ]
    The ASIA score was developed by the American Spinal Injury Association for the neurologic assessment of participants with a spinal injury. In this study, only the ASIA lower extremity motor score was assessed. This comprised five muscle groups scored from 0-5 on both the left and right lower extremities, for a maximal total score of 50. The ASIA scores were categorized as: mild (ASIA score 41-50), moderate (ASIA score 26-40), or severe (ASIA score <=25).
  • Number of Participants With Clinical Composite of All Cause Mortality, Stroke, Spinal Infarction, MI, Need for Dialysis/Sustained Doubling of Serum Creatinine [ Time Frame: Up to Follow-up (Day 45) ]
    The clinical composite event rate included all-cause mortality (death), stroke, spinal infarction (paraplegia which was due to spinal infarct a result of the surgery, myocardial infarction, and the need for dialysis or sustained doubling of serum creatinine (acute kidney injury). The clinical composite endpoint used a first occurrence approach, i.e. a composite event was recorded at the time of first occurrence of any component of the composite.
  • Assessment in AUC for Markers of Ischemic Organ Injury Including Tropinin Within 48 Hours [ Time Frame: Baseline (Day 0) and 8 to 48 hours following DTA/TAAA repair ]
    AUC from 8 hours post surgery (up to 48 hours post surgery) was derived for markers of ischemic organ injury troponin I and troponin T. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • Number of Participants With Composite Index of All Cause Mortality and Disability (NIHSS>5/ASIA<40) [ Time Frame: Up to Follow-up (Day 45) ]
    The NIHSS was a systematic assessment tool that provided a quantitative measure of stroke-related neurologic deficit. Ratings for each item are scored with 0 as normal, and there was an allowance for untestable items. The NIHSS scores were categorized as: No event (NIHSS score=0), Mild (NIHSS score 1-4), Moderate (NIHSS score 5-15), or Severe (NIHSS score >15). The ASIA score was developed by the American Spinal Injury Association for the neurologic assessment of participants with a spinal injury. In this study, only the ASIA lower extremity motor score was assessed. This comprised five muscle groups scored from 0-5 on both the left and right lower extremities, for a maximal total score of 50. The ASIA scores were categorized as: mild (ASIA score 41-50), moderate (ASIA score 26-40), or severe (ASIA score <=25). "Composite above" includes participants with NIHSS>5 or ASIA<40 at the 30-day Follow-up or Death.
  • Pharmacokinetic (PK) Parameters in Blood: AUC(0-t) of GSK1278863 [ Time Frame: Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3 ]
    Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • PK Parameters in CSF: AUC(0-t) of GSK1278863 [ Time Frame: Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI ]
    CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • PK Parameters in Blood: Maximum Observed Concentration (Cmax) of GSK1278863 [ Time Frame: Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3 ]
    Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • PK Parameters in CSF: Cmax of GSK1278863 [ Time Frame: Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI ]
    CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • PK Parameters in Blood: Time of Occurrence of Cmax (Tmax) of GSK1278863 [ Time Frame: Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3 ]
    Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • PK Parameters in CSF: Tmax of GSK1278863 [ Time Frame: Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI ]
    CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
  • Number of subjects with adverse event (AEs). [ Time Frame: Up to 45 days ]
    AEs will be collected from the start of Study Treatment and until the follow-up contact
  • Electrocardiogram (ECG) measurement as a measure of safety and tolerability. [ Time Frame: Up to 45 days ]
    Single 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate intervals.
  • Vital sign measurement as a measure of safety and tolerability [ Time Frame: Up to 45 days ]
    Vital sign measurements will include systolic and diastolic blood pressure and pulse rate.
  • Clinical observation by nurses/physician as a measure of safety and tolerability [ Time Frame: Up to 45 days ]
  • Laboratory parameter assessment as a measure of safety and tolerability [ Time Frame: Up to 45 days ]
    Laboratory parameters will include: hematology, clinical chemistry and additional parameters
  • Area-under-the-curve (AUC) for CSF GFAP and S100beta from baseline to 48 hours [ Time Frame: 48 hours ]
    AUC for CSF GFAP and S100beta from baseline to 48 hours will be assessed to measure CNS injury
  • Change from baseline to peak in CSF biomarkers [ Time Frame: 48 hours ]
    Biomarker will include lactate, erythropoietin, tau protein, and neuron-specific enolase
  • Neurologic outcomes assessed by three validated [ Time Frame: Up to 45 days ]
    The NIHSS is a tool that provides a quantitative measure of stroke-related neurologic deficit.
  • Troponin assessment as a measure of ischemic organ injury [ Time Frame: Up to 7 days ]
  • CPK assessment as a measure of ischemic organ injury [ Time Frame: Up to 7 days ]
  • Creatinine assessment as a measure of ischemic organ injury. [ Time Frame: Up to 7 days ]
  • Liver function test as a measure of ischemic organ injury [ Time Frame: Up to 7 days ]
  • Clinical composite of all-cause mortality, stroke, spinal infarction, myocardial infarction, need for dialysis/sustained doubling of serum creatinine [ Time Frame: Up to 45 days ]
  • Composite index of all-cause mortality and disability (NIHSS>5/ASIA<40) [ Time Frame: Up to 45 days ]
  • Composite of PK parameters in blood and CSF [ Time Frame: Up to Day 4 ]
    PK parameters include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration time
Not Provided
Not Provided
 
Study of GSK1278863 to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair
A Phase II, Randomized, Placebo-Controlled, Double-Blind (Sponsor Open) Study of GSK1278863, a HIF-Prolyl Hydroxylase Inhibitor, to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair
This study will test the hypothesis that GSK1278863 will reduce neurologic, renal, and/or cardiac ischemia in patients undergoing elective descending thoracic aorta/thoracoabdominal aortic aneurysm (DTA/TAAA) repair, a population known to be at high risk for ischemic events from their underlying pathology and the surgical complexity required to address their disease. Approximately 160 subjects will be stratified according to intervention type (surgical or endovascular repair, with the latter limited to 50% of the total study population) and randomized in a 1:1 fashion to treatment with GSK1278863 (300 milligrams [loading dose] followed by 100 milligrams [mg]/day x 4 days) or placebo starting prior to planned repair, through postoperative day 3. The duration of participation in this study is expected to be approximately 4 to 8 weeks from screening to follow-up.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Surgical Procedures
  • Drug: GSK1278863
    White, round biconvex, film coated tablet with unit dose strength of 100 mg for oral administration
  • Drug: Placebo
    White, round biconvex, film coated GSK1278863 matching placebo tablet for oral administration
  • Experimental: GSK1278863
    Subject will receive GSK1278863 300mg on Day-1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100mg once daily for 4 days starting from Day 0.
    Intervention: Drug: GSK1278863
  • Placebo Comparator: Placebo
    Subject will receive GSK1278863 matching placebo on Day-1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 matching placebo once daily for 4 days starting from Day 0.
    Intervention: Drug: Placebo
Aftab M, Coselli JS. Renal and visceral protection in thoracoabdominal aortic surgery. J Thorac Cardiovasc Surg. 2014 Dec;148(6):2963-6. doi: 10.1016/j.jtcvs.2014.06.072. Epub 2014 Jul 21. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
57
October 8, 2014
October 8, 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria

  • Adults >= 18 years of age who require the following types of descending thoracic aorta or thoracoabdominal aorta repair for atherosclerotic aneurysm or chronic dissection (de novo Type B or residual Type B [following Type A repair]) via open surgery or endovascular stenting (TEVAR) as per their treating surgeon
  • Open surgery:

Extent I TAAA (+/-distal arch) if it extends to or beyond renal ostia. Extent II TAAA (+/-distal arch). Extent III TAAA (defined as proximal extent or anastamosis superior to inferior pulmonary vein).

Extent IV TAAA only with a prior TEVAR or if it is a redo procedure (in this setting a "redo" is a prior abdominal aortic aneurysm (AAA) open or endovascular aortic repair (EVAR), with either proximal suture line disruption or mesenteric segment aneurysm recurrence requiring redo Extent IV reconstruction).

DTA repair with one of the following: Safi extent C coverage. Subclavian to diaphragm disease extent. >75% of total DTA length.

-TEVAR with one of the following: Full DTA coverage with previous abdominal EVAR or open AAA. Full DTA coverage including Zone 2 to celiac (i.e., distal arch plus full coverage DTA).

Full DTA coverage with celiac artery coverage with or without left subclavian artery coverage (Zone 2 or Zone 3 proximal landing), or full DTA (either Zone 2 or Zone 3) with extension distal to celiac with visceral debranching (e.g., the abdominal hybrid Extent 2 TAAA).

Note: Zone 2 is defined as between the left carotid through coverage of the left subclavian artery and Zone 3 is defined as the first 3cm distal to the left subclavian (e.g., between left subclavian and ligamentum [isthmus]).

  • Completed any staging or bypass procedure that precedes the aortic repair at least 48 hours prior to the repair.
  • Expect placement of a lumbar CSF catheter during the procedure with plans to maintain it for at least 48 hours per the treating physician.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • A female subject is eligible to participate if she is of:

Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli international unit /mililiter (mL) and estradiol < 40 picogram/mL (<147 picomoles/Liter) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the 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 enrollment. For most forms of HRT, at least 2-4 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.

Child-bearing potential and agrees to use one of the contraception methods from screening until completion of the Follow-up Visit.

  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of Screening until the completion of the Follow-up Visit.

Exclusion Criteria

  • The subject has a traumatic aortic dissection.
  • The subject has a baseline NIHSS > 1 or modified Rankin Scale > 1.
  • The subject has a history of myocardial infarction, stroke, or spinal infarct within the past 3 months.
  • The subject has active ulcer disease or recent gastrointestinal bleeding within the past 6 months.
  • The subject has a history of deep venous thrombosis or pulmonary embolism in the past 12 months.
  • The subject has been treated for a malignancy (excluding non-melanomatous skin cancers) within the past 12 months and is not confirmed to be disease free.
  • The subject has had treatment for retinal neovascularization (e.g., diabetic proliferative retinopathy or age related macular degeneration) within 3 months of randomization.
  • The subject is currently receiving dialysis.
  • The subject is currently receiving or expected to require treatment (within the study period) with erythropoiesis medication such as epoetin alfa (Procrit, Epogen), or darbepoetin alfa (Aranesp).
  • The subject has any of the following at screening:

Hemoglobin >15.5 gram (g)/decilitre (dL) (male subjects or post-menopausal females) Hemoglobin >14.5 g/dL (pre-menopausal female subjects) Single QTc >=480 millisecond (msec); or QTc >=500 msec in subjects with bundle branch block (these criteria do not apply to subjects with predominately paced rhythms) Aspartate aminotransferase and alanine aminotransferase >=2xupper limit of normal (ULN); alkaline phosphatase and bilirubin >=1.5xULN (isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) A positive pre-study drug/alcohol screen Lactation or pregnancy (as determined by positive serum or urine hCG test)

  • The use of prohibited medications
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. 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.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT01920594
116097
Yes
Not Provided
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP