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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Participants 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). |
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| Sequence 2 | Experimental | Participants will receive the study treatment in the following order: BCADFE in each period (one per period) |
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| Sequence 3 | Experimental | Participants will receive the study treatment in the following order: CDBEAF in each period (one per period) |
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| Sequence 4 | Experimental | Participants will receive the study treatment in the following order: DECFBA in each period (one per period) |
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| Sequence 5 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK961081 | Drug | Dry white to off white powder |
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| Measure | Description | Time Frame |
|---|---|---|
| GSK961081 AUC(0-t') | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | 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 | 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 |
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Inclusion Criteria:
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.
QT duration corrected for heart rate by Fridericia's formula (QTcF) less than 450 millisecond.
Exclusion Criteria:
An average weekly intake of greater than 21 units for males or greater than 14 units for females. In Australia one unit (= standard drink) is equivalent to 10 gram of alcohol: 270 mL of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100 mL of wine (13.5%) and 30 mL of spirit (40%).
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Randwick | New South Wales | 2031 | Australia |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| Results for study 201010 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 201010 | Study Protocol | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C588122 | batefenterol |
| C523187 | fluticasone furoate |
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| Experimental |
Participants will receive the study treatment in the following order: EFDACB in each period (one per period) |
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| Sequence 6 | Experimental | Participants will receive the study treatment in the following order: FAEBDC in each period (one per period) |
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| Fluticasone furoate | Drug | Dry white powder |
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| AUC(0-t') and Cmax following single and dual strip administration of GSK961081 |
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 |
| 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 |
| AUC(0-t') and Cmax following concurrent administration of GSK961081 and fluticasone furoate | 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 | 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 |
| Fluticasone furoate AUC(0-t') and Cmax | 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 | 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 |
| Number of participants with Adverse Events | Safety and tolerability as assessed by number of participants with Adverse Events | Up to 12 Weeks |
For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201010 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |