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Epelsiban is a potent and selective oxytocin receptor antagonist in development for enhanced implantation rates during in-vitro fertilization (IVF). This study a non-randomized, open label study designed to assess the safety, tolerability and pharmacokinetics of additional repeat doses of epelsiban in healthy females, and will be the first dosing experience of greater than 200 milligram (mg) as a single dose with this compound. Data from this study will inform the selection of doses of epelsiban to be used in future clinical studies. This study will be composed of 3 periods: Screening, Treatment, and Follow-up. The total duration that a subject involved in the study will be up to 6 weeks. At least 2 cohorts of subjects will be enrolled in this study and cohorts will be conducted sequentially. Additional cohorts will be enrolled if determined necessary. A sufficient number of subjects will be screened for the study to obtain approximately 6 evaluable subjects per cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epelsiban Cohort 1 | Experimental | Subjects will receive 300 mg of epelsiban administered orally twice (every 12 hr) on Day 1 (total daily dose of 600 mg) |
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| Epelsiban Cohort 2 | Experimental | Epelsiban dose for Cohort 2 will be determined based on data from Cohort 1, but will not exceed a total daily dose of 900 mg, administered orally in divided doses (450 mg every 12 hrs or 300 mg every 8 hrs). |
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| Additional Cohorts TBD (to be decided) | Experimental | Subjects will be enrolled if determined necessary, based on data collected in Epelsiban Cohort 1 and Cohort 2 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epelsiban | Drug | Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet. |
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| Measure | Description | Time Frame |
|---|---|---|
| Composite pharmacokinetic parameters of epelsiban and its metabolite (GSK2395448) | Pharmacokinetic parameters including area under the plasma drug (and metabolite) concentration versus time curve (AUC[0-t], AUC[0- infinity], AUC[0-tau]), maximum observed concentration (Cmax), time to maximum observed plasma drug (and metabolite) concentration (tmax), and terminal half-life (t1/2), as data permit, will be analyzed. Blood samples for pharmacokinetic analysis will be collected on Day 1 (Morning pre-dose and 0.5hour(hr), 1 hr, 4 hr, 6hr, 8 hr, 12 hr post morning dose; evening pre-dose and 12.5 hr, 13 hr post morning dose) and Day 2 (16 hr and 24 hr post Day 1 morning dose). | Up to Day 2 |
| Number of subjects with Adverse events (AEs) | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. | Up to Day 12 |
| Assessment of clinical observations | Up to Day 12 | |
| Assessment of hematology parameters | Hematology parameters include complete blood count with red blood cell indices, white blood cell count differential, hemoglobin, hematocrit and platelet count. | Up to Day 12 |
| Assessment of clinical chemistry parameters | Clinical chemistry parameters includes glucose, blood urea, creatinine, sodium, potassium, calcium, total protein, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. | Up to Day 12 |
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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 | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28556598 | Derived | Mahar KM, Enslin MB, Gress A, Amrine-Madsen H, Cooper M. Single- and Multiple-Day Dosing Studies to Investigate High-Dose Pharmacokinetics of Epelsiban and Its Metabolite, GSK2395448, in Healthy Female Volunteers. Clin Pharmacol Drug Dev. 2018 Jan;7(1):33-43. doi: 10.1002/cpdd.363. Epub 2017 May 26. |
| Label | URL |
|---|---|
| Results for study 201691 can be found on the GSK Clinical Study Register. | View source |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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| ID | Term |
|---|---|
| C571185 | epelsiban |
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| Assessment of urinalysis by dipstick | Urinalysis includes specific gravity, pH, glucose, protein, blood and ketones by dipstick. If blood or protein is abnormal microscopic examination will be done. | Up to Day 12 |
| Assessment of vital sign measurements | Vital sign measurements will include temperature, systolic and diastolic blood pressure and heart rate. | Up to Day 12 |
| Assessment of 12-lead electrocardiogram (ECG) | Triplicate 12-lead ECGs will be obtained at each timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. | Up to Day 12 |
| Assessment of physical examination findings | A physical examination will include, at a minimum, assessment of the cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight will also be measured | Up to Day 12 |