Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Respiratory, GSK961081 (MABA), healthy subjects, pharmacokinetics, GW685698 (fluticasone furoate)
Brief summary
GSK961081 is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule and is in development for the treatment of chronic obstructive pulmonary disease (COPD). This is a randomised, open-label, six-way crossover, single dose study. This study evaluates the drug delivery and systemic pharmacokinetics of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via dry powder inhaler (DPI) in comparison to GSK961081 DISKUS. There will be six treatment periods and 7 days washout period in the study. Subjects will attend the unit in the morning for dosing and will be resident until 12 hours post administration. All subjects will receive six treatments.
Interventions
DRUGGSK961081
Dry white to off white powder
DRUGFluticasone furoate
Dry white powder
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Male/females aged between 18 and 64 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigator determines that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body mass index (BMI) within the range 18 to 29.0 kilogram (kg)/meter (m)\^2 (inclusive). * 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 for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/mL and estradiol less than 40 picogram (pg)/mL (less than 147 pmol/L) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use 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 with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening or urine hCG test prior to dosing AND Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for 5 terminal half-lives after the end of the study (i.e. until after the follow-up visit is complete). OR has only same-sex partners, when this is her preferred and usual lifestyle. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form * Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x upper limit of normal (ULN) (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). * Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 85% predicted and a FEV1/ Forced Vital capacity (FVC) ratio greater than or equal to 0.7 * Based on single or averaged QTc values of triplicate Electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF) less than 450 millisecond.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Pre dose, 5 min, 15 min, 30 min, 45 min, 1 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 maximum observed concentration (Cmax) of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via DPI in comparison to GSK961081 DISKUS |
| AUC(0-t') and Cmax following single and dual strip administration of GSK961081 | Pre dose, 5 min, 15 min, 30 min, 45 min, 1 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 AUC(0-t') and Cmax of GSK961081 following single and dual strip administration of GSK961081 alone via DPI in comparison to GSK961081 DISKUS |
| AUC(0-t') and Cmax following concurrent administration of GSK961081 and fluticasone furoate | Pre dose, 5 min, 15 min, 30 min, 45 min, 1 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 AUC(0-t') and Cmax of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via DPI in comparison to single and dual strip GSK961081 via DPI |
| Fluticasone furoate AUC(0-t') and Cmax | Pre dose, 5 min, 15 min, 30 min, 45 min, 1 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 AUC (0-t') and Cmax of fluticasone furoate following concurrent administration of GSK961081 and fluticasone furoate via DPI in comparison to dual strip fluticasone furoate via DPI |
| Number of participants with Adverse Events | Up to 12 Weeks | Safety and tolerability as assessed by number of participants with Adverse Events |
Countries
Australia
Outcome results
None listed