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Dose 1 GSK2586881

Phase 2

Lung Injury, Acute | Small molecule | Other |GSK plc|Last Updated: Sep 28, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials1
Total Enrollment44
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01597635The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung InjuryPHASE2 COMPLETED 44Sep 1, 2012Oct 6, 2014Sep 28, 201719 United States, Canada
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Study Endpoints
Primary Endpoints
Heart Rate Assessments Upto Day 7 (Part B)
Up to Day 7

Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
Up to Day 7

Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
Up to Day 7

Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
Up to Day 7

Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
Up to Day 7

Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
Up to Day 7

Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
Up to Day 7

Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
Up to Day 7

Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
Up to Day 7

Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
Up to Day 7

Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
Up to Day 7

Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
Up to Day 7

Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
Up to Day 7

Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
Up to Day 7

An AE is defined as any untoward medical occurrence in a participant or clinical investigation 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 defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
Up to Day 7

An AE is defined as any untoward medical occurrence in a participant or clinical investigation 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 defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Secondary Endpoints
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)
Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Part AEXPERIMENTAL4 increasing doses of GSK2586881 given over 2 days
Part BEXPERIMENTALRepeat Medium-High dose of GSK2586881 (or placebo) over 3 days
Interventions
NameTypeDescription
Dose 1 GSK2586881DRUGLow dose GSK2586881 administered intravenously
Dose 2 GSK2586881DRUGMedium dose GSK2586881 administered intravenously
Dose 3 GSK2586881DRUGMedium-High dose GSK2586881 administered intravenously
Dose 4 GSK2586881DRUGHigh dose GSK2586881 administered intravenously
Placebo (saline)DRUGAdministered intravenously to match intervention
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Eligibility Criteria
Age Range18 Years — 80 Years
SexALL
Healthy VolunteersNo
Study Sites19

Inclusion Criteria: * Male or female, 18 - 80 years of age (inclusive) * Diagnosis of ALI with acute onset of PaO2/FiO2 ratio less than or equal to 300, and bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asy...

Countries:United StatesCanada
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