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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet.
GSK Investigational Site
Overland Park, Kansas, United States
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).
Time frame: 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.
Time frame: Up to Day 12
Assessment of clinical observations
Time frame: 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.
Time frame: 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.
Time frame: Up to Day 12
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.
Time frame: Up to Day 12
Assessment of vital sign measurements
Vital sign measurements will include temperature, systolic and diastolic blood pressure and heart rate.
Time frame: 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.
Time frame: 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
Time frame: Up to Day 12
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