Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Epelsiban Administered in Repeat Doses in Healthy Women Volunteers

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Embryo Transfer

Treatments: Drug: Epelsiban (GSK557296); Drug: Placebo to match GSK557296

Study type: Interventional

Funder types: Industry

Identifiers

NCT02703181

201752

Details and patient eligibility

About

The current study is designed to assess the safety, tolerability and pharmacokinetics (PK) of additional repeat doses of epelsiban in healthy females, and will be the first dosing experience of repeat dosing at higher doses in women with this compound.

This study is a 14 day, randomized, placebo-controlled, double blind (sponsor unblind), repeat dose, ascending cohort, dose escalation study in healthy, female volunteers. Upon successful completion of the Screening period, a subject will be enrolled in the study. The study will be composed of three periods: Screening, Treatment and Follow-up. A subject's total time involved in the study will be approximately six weeks.

Cohorts will be conducted sequentially. Each subject will be enrolled in only one cohort. Ten subjects will be enrolled in each cohort and randomized to epelsiban (n=8) or placebo (n=2).

Enrollment: 31 patients

Sex: Female

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Female 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 electrocardiogram (ECG).
• Body mass index (BMI) within the range 18 - 35 kilogram per squared meter (kg/m^2) (inclusive)
• 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 defined as: Pre-menopausal females, postmenopausal, or women of reproductive potential who agree to follow one of the options listed in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential.

Exclusion criteria

• History of clinically significant abnormal transvaginal ultrasound
• Alanine aminotransferase (ALT) and bilirubin >1.5 x 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 interval (QTc) > 450 milliseconds (msec)
• History of regular alcohol consumption within three months of dosing on Day 1 defined as: an average weekly intake of >7 drinks. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 milliliters [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 three 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.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a known to inhibit or induce Cytochrome P450 3A4 [P450 CYP3A4]) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within three months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen.
• A positive test for human immunodeficiency virus (HIV) antibody.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within three 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

---

31 participants in 1 patient group

Cohort 1(600 mg Epelsiban or placebo[every 8 hours])

Experimental group

Description:

Each subject will receive 200 mg of epelsiban administered TID (every 8 hours) (total daily dose of 600 mg) or a matching placebo administered every 8 hours.

Treatment:

Drug: Epelsiban (GSK557296)

Drug: Placebo to match GSK557296