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The purpose of this study is to demonstrate dose proportionality of the FF (50 microgram (mcg), 100 mcg or 200 mcg), when administered as a single and repeat dose from the NDPI containing FF formulated with lactose. In addition, the aim of this study is to determine the absolute bioavailability of the FF single strip product using the high strength product administered as a single dose with multiple inhalations and using 250 mcg intravenous (IV) FF.
This is a, part-randomized, open-label, 4 way crossover study (4 periods) in healthy adult subjects. During each period, subjects will receive FF in the morning and serial pharmacokinetic (PK) sampling (for up to 10 days for the inhaled treatment and up to 3 days for the IV treatment) and safety assessments will be performed. Each period will be separated by a washout period of at least 7 days and a follow-up telephone call will occur 7 -14 days after the last dose of study drug. The total duration of the study will be approximately 13-14 weeks for each subject.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FF 50 mcg powder inhalation | Experimental | Each subject will receive a single dose of 300 mcg FF (6 inhalations of 50 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 50 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI. |
|
| FF 100 mcg powder inhalation | Experimental | Each subject will receive a single dose of 600 mcg FF (6 inhalations of 100 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 100 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI. |
|
| FF 200 mcg powder inhalation | Experimental | Each subject will receive a single dose of 1200 mcg FF (6 inhalations of 200 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 200 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI. |
|
| FF 250 mcg IV | Experimental | Each subject will receive a single dose of 250 mcg FF, administered as an IV infusion over 20 minutes on Day 1 of the respective period per randomization sequence. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FF, 50 mcg | Drug | Novel dry powder inhaler |
| |
| Measure | Description | Time Frame |
|---|---|---|
| FF pharmacokinetics; parameters: (AUC(0-infinity)) , (AUC(0-24)) and (Cmax) | FF pharmacokinetics; area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC (0-infinity)), area under the concentration-time curve from zero (pre-dose) to 24 h (AUC (0-24)) and maximum observed concentration (Cmax). Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology. | 54 days |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma FF PK parameters: t1/2, tmax, MRT for all treatments | Following plasma FF PK parameters will be evaluated: terminal phase half life (t1/2), time of occurrence of Cmax (tmax), mean residence time (MRT) for all treatments Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Groningen | 9713 GZ | Netherlands |
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| Label | URL |
|---|---|
| Results for study 115441 can be found on the GSK Clinical Study Register. | View source |
| 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 |
| ID | Type | URL | Comment |
|---|---|---|---|
| 115441 | Annotated Case Report Form | 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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| FF, 100 mcg |
| Drug |
Novel dry powder inhaler |
|
| FF, 200 mcg | Drug | Novel dry powder inhaler |
|
| FF, 250 mcg | Drug | Intravenous |
|
| 54 days |
| Plasma FF PK parameters: V and CL for IV treatment | Following plasma FF PK parameters will be evaluated: volume of distribution (V) and plasma clearance (CL) for intravenous administration Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology. | 3 days (Study Day 52 to Study Day 54) |
| Mean absorption time (MAT) for inhaled treatments | Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology. | 44 days |
| Safety of FF | To assess the safety and tolerability of FF administered as single and repeat dose adverse events will be studied. | 68 days |
For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115441 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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