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GSK557296 is being studied in women for the indication of enhanced embryo and or blastocyst implantation in women undergoing IVF treatment. This study will be the first dosing experience with this compound in women. It is important to characterize the pharmacokinetics of GSK557296 in women to determine the most appropriate doses and dosing regimens for future clinical studies. Understanding the pharmacokinetics of GSK557296 in women will also enable more accurate characterization of any exposure-response relationship in future studies.
Two previous studies with GSK557296 were conducted in men with oral doses ranging from 10 milligram (mg) to 200 mg. GSK557296 is being studied in women for the indication of enhanced embryo and or blastocyst implantation in women undergoing IVF treatment. This is a bridging study to characterize the pharmacokinetics of GSK557296 in women to determine the most appropriate doses and dosing regimens for future clinical studies.
This is a non-randomized, open label, adaptive design study in healthy female volunteers. A maximum total of 48 subjects, will participate in different cohorts. Subjects in Cohort 1 will receive 10 mg single dose followed by repeat dose. A one week break will occur to allow for analysis of the PK data, prior to starting the second Cohort. Subjects in Cohort 2 will receive 150 mg single dose followed by repeat dose. Cohort 3 and Cohort 4 were adaptive based on the requirement of additional doses to be studies after PK data will be analyzed from each of the first 2 cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: GSK557296 10 mg | Experimental | GSK557296 10 mg single dose on Day 1 followed by repeat dosing (4 times a day) on Days 2-6 |
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| Cohort 2: GSK557296 150 mg | Experimental | GSK557296 150 mg as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in treatment A) on Days 9-13 |
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| Cohort 3 | Experimental | This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 2. Subjects in this optional Cohort 3 will receive GSK557296 (dose to be determined) as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in Cohort 1 and Cohort 2) on Days 2-6 |
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| Cohort 4 | Experimental | This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 1. Subjects in this optional Cohort 4 will receive GSK557296 (dose to be determined) by PK of prior doses, 10-150 mg single dose on Day 1 followed by repeat dosing (either 2, 3 or 4 times a day dependent on half-life demonstrated in prior groups) on Days 2-6 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK557296 10 mg | Drug | 10 mg single oral dose. Each subject will receive 2 tablets of 5 mg GSK557296 four times a day (QID). |
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| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters of 20 mg GSK557296 following single and repeat oral dosing | From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0-infinity) or AUC(0-Ï„) and Cmax following single and repeat doses may be used for assessment of dose proportionality. | 7 days |
| Composite of PK parameters of 150 mg GSK557296 following single and repeat oral dosing | From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0- infinity) or AUC(0-Ï„) and Cmax following single and repeat doses may be used for assessment of dose proportionality. | 14 days |
| Safety and tolerability of GSK557296 following single and repeat dosing | Safety and tolerability parameters assessments include adverse events, clinical laboratory, ECG, vital signs, and concurrent medication | up to 49 days |
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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 | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27137713 | Derived | Mahar KM, Stier B, Fries M, McCallum SW. A single- and multiple-dose study to investigate the pharmacokinetics of epelsiban and its metabolite, GSK2395448, in healthy female volunteers. Clin Pharmacol Drug Dev. 2015 Nov;4(6):418-26. doi: 10.1002/cpdd.210. Epub 2015 Aug 26. |
| 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 |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116741 | Clinical Study Report | 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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| GSK557296 150 mg | Drug | 150 mg single oral dose. Each subject will receive multiple tablets of 25 mg GSK557296 either 2, 3 or 4 times a day. |
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| GSK557296 dose 3 | Drug | Dose to be determined as a single dose tablet based on half-life demonstrated in Cohort 1 and Cohort 2. |
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| GSK557296 dose 4 | Drug | Dose to be determined by PK of prior doses, based on half-life demonstrated in prior cohorts. |
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| Results for study 116741 can be found on the GSK Clinical Study Register. | View source |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116741 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| C571185 | epelsiban |
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