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Tiotropium + SERETIDE 50/500

Phase 3

Pulmonary Disease, Chronic Obstructive | Small molecule | Other |GSK plc|Last Updated: Feb 15, 2018

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-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials3
Total Enrollment477
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01395888A Study to Compare the Impact of Fulticasone Furoate/Vilanterol vs. Tiotropium on Arterial Stiffness in COPDPHASE3 COMPLETED 260Jun 30, 2011Aug 6, 2012Feb 15, 201855 Argentina, France +5
NCT00950807GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary DiseasePHASE2 COMPLETED 176Sep 1, 2009Mar 15, 2010Nov 8, 201719 United States, Germany
NCT00325169SERETIDE Plus Tiotropium Versus Individual ComponentsPHASE2 COMPLETED 41Dec 1, 2005Aug 1, 2006Oct 21, 20165 Belgium, United Kingdom
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Study Endpoints
Primary Endpoints
Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 12-week Treatment Period (Day 84)
Baseline to Day 84 (Early Withdrawal)

PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of Eh/2pR, where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and p is the blood density. Change from Baseline was calculated as the Day 84 value minus the Baseline value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking status at screening, geographical region, Baseline aPWV, and interaction terms of Baseline by visit and treatment by visit.

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
Baseline and Day 15 of each treatment period (up to Study Day 71)

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were performed using a mixed model with covariates of mean Baseline, period Baseline, treatment and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.

AUC (0-4hrs, sGAW after morning dose of medication at day 14)
Secondary Endpoints
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period
Baseline and Day 14 of each treatment period (TP; up to Study Day 70)
Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)
Effects of SERETIDE 50/500mcg twice daily plus tiotropium bromide 18mcg once daily compared with the individual treatments on further elements of lung function, dyspnoea, symptoms and a patient/physician assessment of treatment effect.
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
RelovairEXPERIMENTALInhaled long-acting bronchodilator and corticosteroid combination
TiotropiumACTIVE_COMPARATORInhaled long-acting anticholinergic
PlaceboPLACEBO_COMPARATORPlacebo
Arm 1EXPERIMENTALGSK573719 1000mcg once daily
Arm 2EXPERIMENTALGSK573719 500mcg once daily
Arm 3EXPERIMENTALGSK573719 250mcg once daily
Arm 4EXPERIMENTALGSK573719 125mcg once daily
Arm 5EXPERIMENTALGSK573719 62.5 mcg once daily
Arm 6EXPERIMENTALGSK573719 250mcg twice daily
Arm 7EXPERIMENTALGSK573719 125mcg twice daily
Arm 8EXPERIMENTALGSK573719 62.5mcg twice daily
Interventions
NameTypeDescription
fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Novel Dry Powder Inhaler (NDPI)DRUGfluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Inhalation Powder delivered once daily via a Novel Dry Powder Inhaler (NDPI)
TiotropiumDRUG• Tiotropium (18 mcg) administered QD via a HandiHaler
PlaceboDRUGInactive/ excipients only
GSK573179DRUGGSK573179 investigational drug
Tiotropium + SERETIDE 50/500DRUG -
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Eligibility Criteria
Age Range40 Years — 80 Years
SexALL
Healthy VolunteersNo
Study Sites55

Inclusion Criteria: * Type of subject: Outpatient * Informed consent: Subjects must give their signed and dated written informed consent to participate. * Gender: Male or female subjects. * Age: greater then or equal to 40 years of age at Screening (Visit 1) * COPD diagnosis: Subjects with a clinic...

Countries:ArgentinaFranceGermanyItalyNorwayRussiaUkraineUnited StatesBelgiumUnited Kingdom
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