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GW642444M

Phase 2

Pulmonary Disease, Chronic Obstructive | Small molecule | Other |GSK plc|Last Updated: Mar 23, 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 Trials2
Total Enrollment34
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00519376A Study To Investigate The Effect Of Inhaling A Single Dose Of GW642444M In COPD Patients.PHASE2 COMPLETED 20Aug 1, 2007Nov 1, 2007Mar 23, 20174 Germany
NCT00381667Study to Assess GW642444 in Asthma PatientsPHASE2 COMPLETED 14Aug 1, 2006Jan 1, 2007Oct 28, 20162 Australia, New Zealand
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Study Endpoints
Primary Endpoints
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
From the first dose of the study medication until the Follow-up Visit (up to Study Day 60)

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. A serious adverse event (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, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cell Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, and white blood cell (WBC) count at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of hemoglobin and MCHC at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Reticulocyte and Red Blood Cell (RBC) Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of reticulocyte and RBCs at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Hematocrit at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of hematocrit at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Mean Corpuscle Volume (MCV) at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of MCH at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Albumin and Total Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of albumin and total protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Cholesterol, Chloride, Potassium, Sodium, Triglycerides, and Urea at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of cholesterol, chloride, potassium, sodium, triglycerides, and urea at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Total Bilirubin and Creatinine at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in C-reactive Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Blood samples were collected for the measurement of c-reactive protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over the Post-dose 24 Hour (h) Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

SBP and DBP were measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1h, 2h, 3h, 4h, 6h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Heart Rate Over the Post-dose 24 Hour (h) Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

Heart rate (HR) was measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Change From Baseline in Electrocardiographic (ECG) Parameters Over the Post-dose 24 Hour (h) Period
Baseline and Day 1 of each treatment period (up to Study Day 54)

ECG parameters \[PR, QRS, RR, QT (uncorrected), QTcB (QT corrected by Bazett's formula) and QTcF (QT corrected by Fridericia's formula) intervals\] were measured at Baseline and over the post-dose 24h period at the following scheduled time points: 20 minutes (min), 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline was defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Adverse events
throughout study
Laboratory safety tests
throughout study
Holter monitoring
throughout study
Vital signs and 12-lead ECG)
throughout study
Mean change from baseline FEV1 24 hours after dosing.
Day 1, on 5 separate occasions
Supine systolic and diastolic blood pressure and supine heart rate
Day 1 on 5 separate occasions
QTc(B)and QTc(F)
Day 1 on 5 separate occasions
Secondary Endpoints
Mean FEV1 Over 23 and 24 Hours After Dosing
Baseline and Day 1 of each treatment period (up to Study Day 54)
Weighted Mean and Maximum Value (0 - 4 Hours) QTc(B) and QTc(F)
Baseline and Day 1 of each treatment period (up to Study Day 54)
Weighted Mean and Maximum Value (0 - 4 Hours) Supine Heart Rate
Baseline and Day 1 of each treatment period (up to Study Day 54)
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelCROSSOVER
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
GW642444M 25mcgEXPERIMENTAL -
GW642444M 50mcgEXPERIMENTAL -
GW642444M 100mcgEXPERIMENTAL -
GW642444H 100mcgEXPERIMENTAL -
placeboEXPERIMENTAL -
GW642444M 12.5EXPERIMENTAL -
GW642444M 400mcgEXPERIMENTAL -
Interventions
NameTypeDescription
GW642444MDRUGdrug
GW642444HDRUGdrug
placeboDRUG -
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Eligibility Criteria
Age Range40 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites4

Inclusion criteria: * Male or female (of non-childbearing potential) \> or = 40 years * History of COPD * Smoker or ex-smoker * Body weight \> or = 50 kg with BMI 18-32 kg/m2 Exclusion criteria: * History of significant disease * Subjects with a primary asthma diagnosis * Alpha-1 antitrypsin defi...

Countries:GermanyAustraliaNew Zealand
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