Clinical trial NCT02257359: Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Epelsiban in Healthy Female Volunteers
Official title: A Phase 1, Open Label, Ascending Cohort, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Epelsiban and Its Metabolite in Healthy Female Volunteers Following Administration of Epelsiban
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Embryo Transfer
Keywords: Epelsiban
Healthy Female Volunteers
Safety
Tolerability
Oxytocin
Pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-10-06
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Females between 18 and 55 years of age inclusive, at the time of consent.
* Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, review of medications previously used, physical examination, laboratory tests and ECG.
* Body mass index (BMI) within the range 18-35 kilogram per square meter( kg/m\^2) (inclusive).
* Female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential or postmenopausal.

Exclusion Criteria

* Alanine Transferase (ALT) and bilirubin \>1.5x upper limit of normal(ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Corrected QT (QTc) \> 450 milliseconds (msec). - History of regular alcohol consumption within 3 months of dosing on Day 1 defined as: an average weekly intake of \>7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of Study Treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
* A positive pre-study drug/alcohol screen.
* A positive test for human immunodeficiency virus antibody.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Primary outcomes:
measure: Composite pharmacokinetic parameters of epelsiban and its metabolite (GSK2395448)
timeFrame: Up to Day 2
measure: Number of subjects with Adverse events (AEs)
timeFrame: Up to Day 12
measure: Assessment of clinical observations
timeFrame: Up to Day 12
measure: Assessment of hematology parameters
timeFrame: Up to Day 12
measure: Assessment of clinical chemistry parameters
timeFrame: Up to Day 12
measure: Assessment of urinalysis by dipstick
timeFrame: Up to Day 12
measure: Assessment of vital sign measurements
timeFrame: Up to Day 12
measure: Assessment of 12-lead electrocardiogram (ECG)
timeFrame: Up to Day 12
measure: Assessment of physical examination findings
timeFrame: Up to Day 12
Secondary outcomes:
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.