Recent Updates
Recently added Catalysts

GSK961081

Phase 2

Pulmonary Disease, Chronic Obstructive | Small molecule | Other |GSK plc|Last Updated: May 15, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
Premium
Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
Premium
Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials3
Total Enrollment567
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01319019A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)PHASE2 COMPLETED 437Dec 1, 2010Sep 1, 2011Dec 1, 201649 Estonia, Germany +7
NCT00478738A 2 Part Study Examining Doses Of GSK961081 In Healthy Volunteers And Then In COPD PatientsPHASE2 COMPLETED 82Jun 1, 2007May 1, 2008Feb 2, 20175 Germany, South Africa
NCT02064504Study to Determine the Pharmacokinetics of GSK961081 and Fluticasone Furoate When Administered Alone or in CombinationPHASE1 COMPLETED 48Feb 19, 2014May 20, 2014May 15, 20171 Australia
Unlock Drug Trial Details
Study Endpoints
Primary Endpoints
Change in FEV1 from baseline in pre-dose AM trough.
28 Day

Pre-dose change in AM FEV1 on day 29 vs baseline . (defined as the mean values recorded 11 and 12 hours after the PM dose on day 28)

Part 1: Summary of area under the GSK961081 concentration-time curve (AUC) after a single dose
Pre-dose (0.0 hour [h]) and 15, 30, 45 minutes (M), 1, 2, 3, 4, 6, 8, 12 and 24 h post dose of each treatment period

Plasma samples for PK analysis were drawn on Day (D) 1 at indicated time points. The AUC from time zero (0M) to 2h (AUC 0-2) was area under the plasma concentration-time curve over the 2h time period. AUC(0-6) was area under the plasma concentration-time curve from 0M to 6h. AUC(0-t) was area under the plasma concentration-time curve from 0M to last quantifiable concentration. The AUC extrapolated to infinity (inf) (AUC\[0-inf\]) was calculated as the sum of AUC(0-t) and Ct/lambda z, where Ct is the observed GSK961081 concentration obtained from the log-linear regression analysis of the last quantifiable time-point and lambda z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. The number of time points used in the estimation of lambda z. Different participants may have been analyzed at different time points; thus, the overall number of participants analyzed reflects everyone in the PK population.

Part 1: Summary of maximum observed concentration (Cmax) of GSK961081 after a single dose
Pre-dose (0.0h) and 15, 30, 45 M, 1, 2, 3, 4, 6, 8, 12 and 24 h post dose of each treatment period

Plasma samples for PK analysis were drawn on D1 at indicated time points. The first occurrence of the maximum observed GSK961081 concentration determined directly from the raw concentration-time data after each single dose. All participants were present at the time of measurement.

Part 1: Summary of last observed plasma concentration (t-last), time of maximum observed concentration (t-max) and terminal elimination half-life (t-half)
Pre-dose (0.0h) and 15, 30, 45 M, 1, 2, 3, 4, 6, 8, 12 and 24 h post dose of each treatment period

Plasma samples for PK analysis were drawn on D1 at indicated time points. The t-last and t-max was determined directly from the raw concentration-time data after each single dose. The t-half was obtained as the ratio of ln2/lambda z, where ln(2) is the natural logarithm of 2 (approximately 0.693) and lambda z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data after each single dose. Data for adjusted mean is presented as least square mean. Only those participants available at the specified time points were analyzed (represented by n=x,x,x in the category titles). Different participants may have been analyzed at different time points; thus, the overall number of participants analyzed reflects everyone in the All Subjects population.

Part 2: Forced Expiratory Volume in 1 second (FEV1) over 24 hours post-dose on D1 and 14
Up to D14 of each treatment period (up to 16 weeks)

Lung function tests (FEV1) was recorded whilst the participant was in a sitting position (if taken whilst the participant was on the bed, their legs should be over the edge). All lung function tests was repeated, until three technically acceptable measurements were made. Each measurement should be done at least 1 M apart. Participants must be resting in the body box for at least 30 seconds prior to any assessments. The FEV1 was measured at 15, 30 M, 1, 4, 12 and 24 h post dose of each treatment period on D1 and 14. Data for adjusted mean is presented as least square mean. Only those participants available at the specified time points were analyzed (represented by n=x,x,x,x in the category titles). Different participants may have been analyzed at different time points; thus, the overall number of participants analyzed reflects everyone in the All Subjects population. Data for adjusted mean is presented as least square mean.

GSK961081 AUC(0-t')
Pre dose, 5 minutes (min), 15 min, 30 min, 45 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

Blood samples will be collected to estimate the area under the concentration-time curve from zero (pre-dose) to last common time of quantifiable concentration across all treatments for an analyte where t'=common time AUC(0-t') of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via DPI in comparison to GSK961081 DISKUS

Secondary Endpoints
Weighted Mean and Serial FEV1 at multiple timepoints
28 Days
Part 1: Number of participants with Adverse Events (AE) and Serious adverse events (SAE)
Up to 16 weeks
Part 1: Mean values for urea, sodium, potassium, cholesterol, chloride, high density lipids-cholesterol (HDLC), and triglyceride
Up to D1 of each treatment period (up to 16 weeks)
Unlock Study Endpoints
Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
GSK961081 100 mcg QDEXPERIMENTAL -
GSK961081 100mcg BDEXPERIMENTAL -
GSK961081 200mcg QDEXPERIMENTAL -
GSK961081 400mcg QDEXPERIMENTAL -
GSK961081 400mcg BDEXPERIMENTAL -
GSK961081 800mcg QDEXPERIMENTAL -
Salmeterol 50mcg BDACTIVE_COMPARATOR -
PlaceboPLACEBO_COMPARATOR -
GSK961081OTHERGSK961081
Sequence 1EXPERIMENTALParticipants will receive the study treatment in the following order: ABFCED in each period (one per period). Where A=GSK961081 administered from DISKUS, B=GSK961081 Single strip (SS) administered from DPI, C=GSK961081 Dual Strip (DS) administered from DPI with a filled (lactose) second strip (DS configuration), D=GSK961081/fluticasone furoate (GSK961081/FF) administered from DPI (GSK961081 higher dose), E=FF DS administered from DPI with a filled (lactose) second strip (dual strip configuration), F=GSK961081/FF administered from DPI (GSK961081 lower dose).
Sequence 2EXPERIMENTALParticipants will receive the study treatment in the following order: BCADFE in each period (one per period)
Sequence 3EXPERIMENTALParticipants will receive the study treatment in the following order: CDBEAF in each period (one per period)
Sequence 4EXPERIMENTALParticipants will receive the study treatment in the following order: DECFBA in each period (one per period)
Sequence 5EXPERIMENTALParticipants will receive the study treatment in the following order: EFDACB in each period (one per period)
Sequence 6EXPERIMENTALParticipants will receive the study treatment in the following order: FAEBDC in each period (one per period)
Interventions
NameTypeDescription
GSK961081DRUGComparison of different doses and dosing regimens of the drug
SalmeterolDRUGPositive control
PlaceboDRUGPlacebo arm
Fluticasone furoateDRUGDry white powder
Unlock Study Design Details
Eligibility Criteria
Age Range40 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites49

Inclusion Criteria: * Outpatient Subjects * Subjects who give their signed and dated informed consent to participate * 40 or more years of age, inclusive, at Visit 1 * Male or females * Subjects with an established clinical history of COPD * Current or previous cigarette smokers with a history of ≥...

Countries:EstoniaGermanyNetherlandsRomaniaRussiaSlovakiaSouth AfricaSwedenUkraineAustralia
Unlock Eligibility Criteria