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The purpose of this study is to characterize the pharmacokinetics (PK), safety and tolerability of topically applied umeclidinium following single dose topical administration. The results from this study will be used to 1) improve our understanding of the risk of systemic accumulation upon chronic administration, 2) support dosing recommendations in a 2a/2b study for axillary administration and, potentially, a separate combined 2a/2b study for palmar administration, and 3) confirm whether the same formulation can be used for axillary and palmar application for the next studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | Single dose of topical [14C]Umeclidinium was applied to the unoccluded axilla, and the drug which will be applied to the test site has to remain on the application site for 8 hrs |
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| Cohort B | Experimental | Single dose of topical [14C]Umeclidinium was applied to the occluded axilla, and the drug which will be applied to the test site has remain on the application site for 8 hrs |
|
| Cohort C | Experimental | Single dose of topical [14C]Umeclidinium was applied to the unoccluded palm, and the drug which will be applied to the test site has to remain on the application site for 8 hrs |
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| Cohort D | Experimental | Single dose of topical [14C]Umeclidinium was applied to the occluded palm, and the drug which will be applied to the test site has to remain on the application site for 8 hrs |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]Umeclidinium 18.5 mg | Drug | Umeclidinium will be supplied as clear, colorless solution, free from visible particulates, single dose, topical solution in clear glass jars. Dosage of 18.5 mg of Umeclidinium per gram is equivalent to 22 mg per gram of the bromide salt. |
| Measure | Description | Time Frame |
|---|---|---|
| PK Assessment (Cmax) for [14C] umeclidinium and total radioactivity | Blood sample will be collected for PK assessment including maximum observed plasma concentration (Cmax). | Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
| PK Assessment (tmax) for [14C] umeclidinium and total radioactivity | Blood sample will be collected for PK assessment including time to Cmax (tmax). | Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
| PK Assessment (AUC) for [14C] umeclidinium and total radioactivity | Blood sample will be collected for PK assessment including area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable sample (AUC0-last), AUC from time zero to 12 hrs or 24 hrs (AUC0-12 and AUC0-24, respectively), AUC from time zero to time infinity [AUC (0-infinity)]. | Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
| PK Assessment (t1/2) for [14C] umeclidinium and total radioactivity | Blood sample will be collected for PK assessment including apparent terminal phase half-life (t1/2). | Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
| Compartmental modeling of absorption rate for [14C] umeclidinium | Compartmental modeling may be conducted to characterize the absorption rate constants. |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the amount of Umeclidinium absorbed in the skin | Evaluations will be determined by subtracting the amount of drug recovered from skin and tape strips | Day 1 (and Day 2 if required) |
| Safety Assessment for AEs |
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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 | Zuidlaren | 9471 GP | Netherlands |
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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 117157 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 117157 | 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 |
|---|---|
| D006945 | Hyperhidrosis |
| ID | Term |
|---|---|
| D013543 | Sweat Gland Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
| Compartmental modeling of elimination rate for [14C] umeclidinium | Compartmental modeling may be conducted to characterize the elimination rate constants. | Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14. |
Safety evaluations will be based on the incidence, intensity and type of adverse events (AEs)
| From first dose up to Follow-up (Day 14) |
| Safety Assessment for ECGs, and telemetry | Safety evaluations will be based on the 12-lead electrocardiograms (ECGs) and Lead II ECG monitoring. | From Screening up to Follow-up (Day 14) |
| Safety Assessment for hematology laboratory parameters | Safety evaluations will be based on hematology laboratory results | From Screening up to Follow-up (Day 14) |
| Safety Assessment for measurement of blood pressure | Safety evaluations will be based on the clinically significant changes in vital signs includes systolic and diastolic blood pressure | From Screening up to Follow-up (Day 14) |
| Number of subjects with application site skin irritation | Safety evaluations will be based on application site skin irritation. The number of subjects with application site skin irritation (as measured by the Skin Tolerability Assessment Scale) will be summarized. | From Day 1 up to Follow-up (Day 14) |
| Safety Assessment for clinical chemistry laboratory parameters | Safety evaluations will be based on the clinical chemistry laboratory results | From Screening up to Follow-up (Day 14) |
| Safety Assessment for measurement of pulse rate | Safety evaluations will be based on the clinically significant changes in vital signs includes pulse rate | From Screening up to Follow-up (Day 14) |
For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117157 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |