Study to Evaluate the Pharmacokinetics, Safety and Tolerability of GSK557296 in Healthy Women Volunteers After Single and Repeat Dosing

NCT ID: NCT01669083

Last Updated: 2017-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-16
• Study Completion Date: 2013-03-09

Brief Summary

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.

Conditions

Embryo Transfer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: GSK557296 10 mg

GSK557296 10 mg single dose on Day 1 followed by repeat dosing (4 times a day) on Days 2-6

Group Type: EXPERIMENTAL

GSK557296 10 mg

Intervention Type: DRUG

10 mg single oral dose. Each subject will receive 2 tablets of 5 mg GSK557296 four times a day (QID).

Cohort 2: GSK557296 150 mg

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

Group Type: EXPERIMENTAL

GSK557296 150 mg

Intervention Type: DRUG

150 mg single oral dose. Each subject will receive multiple tablets of 25 mg GSK557296 either 2, 3 or 4 times a day.

Cohort 3

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

Group Type: EXPERIMENTAL

GSK557296 dose 3

Intervention Type: DRUG

Dose to be determined as a single dose tablet based on half-life demonstrated in Cohort 1 and Cohort 2.

Cohort 4

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

Group Type: EXPERIMENTAL

GSK557296 dose 4

Intervention Type: DRUG

Dose to be determined by PK of prior doses, based on half-life demonstrated in prior cohorts.

Interventions

GSK557296 10 mg

10 mg single oral dose. Each subject will receive 2 tablets of 5 mg GSK557296 four times a day (QID).

Intervention Type: DRUG

GSK557296 150 mg

150 mg single oral dose. Each subject will receive multiple tablets of 25 mg GSK557296 either 2, 3 or 4 times a day.

Intervention Type: DRUG

GSK557296 dose 3

Dose to be determined as a single dose tablet based on half-life demonstrated in Cohort 1 and Cohort 2.

Intervention Type: DRUG

GSK557296 dose 4

Dose to be determined by PK of prior doses, based on half-life demonstrated in prior cohorts.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN)
• Single or QTcF < 450 millisecond (msec); or QTc < 480 msec in subjects with Bundle Branch Block
• Healthy as determined by a responsible and experienced physician
• Female between 18 and 45 years of age inclusive, at the time of signing the informed consent
• A female subject is eligible to participate if she is of Child-bearing potential and is abstinent or agrees to use contraception methods to sufficiently minimize the risk of pregnancy during the study.
• Body weight >= 50 kilogram (kg) and Body Mass Index (BMI) within the range 19 to 29.9 kg per meter^2 (inclusive)

Exclusion Criteria

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result at screening or within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• A positive pre-study drug or alcohol screen
• A positive test for HIV antibody
• History of regular alcohol consumption within 6 months of the study
• 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 Unable to refrain from the use of prescription or non-prescription drugs, with the exception of Oral contraceptives, within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication 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 GSK Medical Monitor, contraindicates their participation
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56 day period
• Pregnant females
• Lactating females
• Unwillingness or inability to follow the procedures outlined in the protocol
• Subject is mentally or legally incapacitated
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening
• Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pomelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27137713 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

116741

Identifier Type: -

Identifier Source: org_study_id