Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Epelsiban in Healthy Female Volunteers

September 11, 2018 updated by: GlaxoSmithKline

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Epelsiban Cohort 1
Subjects will receive 300 mg of epelsiban administered orally twice (every 12 hr) on Day 1 (total daily dose of 600 mg)
Drug: Epelsiban
Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet.
Experimental: Epelsiban Cohort 2
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).
Drug: Epelsiban
Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet.
Experimental: Additional Cohorts TBD (to be decided)
Subjects will be enrolled if determined necessary, based on data collected in Epelsiban Cohort 1 and Cohort 2
Drug: Epelsiban
Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite pharmacokinetic parameters of epelsiban and its metabolite (GSK2395448)
Time Frame: Up to Day 2
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)
Time Frame: Up to Day 12
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
Time Frame: Up to Day 12
Up to Day 12
Assessment of hematology parameters
Time Frame: Up to Day 12
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
Time Frame: Up to Day 12
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
Assessment of urinalysis by dipstick
Time Frame: Up to Day 12
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
Time Frame: Up to Day 12
Vital sign measurements will include temperature, systolic and diastolic blood pressure and heart rate.
Up to Day 12
Assessment of 12-lead electrocardiogram (ECG)
Time Frame: Up to Day 12
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
Time Frame: Up to Day 12
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 18, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 29, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 29, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 2, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 2, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 6, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 13, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201691

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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