A Study to Evaluate Pharmacokinetics, Pharmacodynamics and Tissue Concentrations of Epelsiban

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02213029
• Date of registration: 07/08/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Evaluate Pharmacokinetics, Pharmacodynamics and Tissue Concentrations of Epelsiban
• Scientific title: Study IVF116828:A Multi-Cohort Phase I Study to Investigate the Pharmacokinetics, Pharmacodynamics and Tissue Concentrations of Epelsiban (GSK557296) in Healthy Female Volunteers During Control and Challenge States With and Without Oxytocin
• Date of first enrolment: August 28, 2014
• Target sample size: 33
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02213029
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

For ultrasound training cohort

- Female volunteers of childbearing potential; with a negative pregnancy test as
determined by human chorionic gonadotropin (hCG) testing at screening and prior to
study initiation.

- Age between 18 and 35 years old (inclusive).

- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18-30
kg/meter (m)^2 (inclusive).

- Normal ovarian and uterine anatomy as assessed by transvaginal ultrasonography.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Is in good physical and mental health as determined by a responsible and experienced
physician, based on a medical evaluation including medical history, and physical
examination.

For Cohorts 1, 2A, 2B, 2C, 3

- Female volunteers of childbearing potential; with a negative pregnancy test as
determined by hCG testing at screening and prior to study initiation.

- Agrees to use one of the contraception methods for 2 weeks prior to the start of study
to minimize the risk of pregnancy. Female subjects must agree to use contraception
until at least 48 hours have passed after the last dose of study drug. OR has only
same-sex partners, when this is her preferred and usual lifestyle. Oral contraceptive
(OC) pill naive or have discontinued OC at least 2 months prior to study entry.

- Age between 18 and 35 years old.

- Body weight >=50 kg and BMI within the range 18-30 kg/m^2 (inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form as signed consent form; and
is in good physical and mental health as determined by a responsible and experienced
physician, based on a medical evaluation including medical history, physical
examination, laboratory tests and cardiac monitoring. A subject with a clinical
abnormality or laboratory parameter(s) which is/are not specifically listed in the
inclusion or exclusion criteria, outside the reference range for the population being
studied may be included only if the Investigator in consultation with the
GlaxoSmithKline (GSK) Medical Monitor if required agree and document that the finding
is unlikely to introduce additional risk factors and will not interfere with the study
procedures.

- Subjects with a blood sample with simultaneous follicle stimulating hormone (FSH) > 40
milli international unit (MI)U/milliliter (mL) and estradiol <40 picogram/mL (<147
picomoles/Liter) should always be excluded from enrolment.

- based on single or averaged corrected QTc values of triplicate ECGs obtained over a
brief recording period: QTc <450 milliseconds (msec); or QTc <480 msec in subjects
with Bundle Branch Block.

Exclusion Criteria:

For Training Cohort

- Ultrasonographic evidence of uterine anomalies, including but not limited to
intramural or submucosal leiomyomas (fibroids) cysts, endometrial polyps, American
Society for Reproductive Medicine (ASRM) Class I-VI uterine malformations or
intrauterine fluid collections.

- Pregnancy (suspected or diagnosed) or lactation.

- Has had a prior partial or total hysterectomy or tubal ligation.

- Currently using and intrauterine device (IUD) for any reason.

- History or suspicion of drug or alcohol abuse. Criteria Based Upon Medical Histories
For Training Cohort

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- History of regular alcohol consumption within 6 months of the study defined as: An
average weekly intake of >7 drinks. One drink is equivalent to 12 grams of alcohol: 12
ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof
distilled spirits.

Criteria Based Upon Diagnostic Assessments For Training Cohort

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- A positive pre-study drug/alcohol/; and.

- A positive test for human immune virus (HIV) antibody. For Cohorts 1, 2A, 2B, 2C, 3

- Female with an abnormal obstetric profile (average durations <27 days or > 31 days;Any
contraindication for oral contraception use; Is using hormone replacement therapy
(HRT); Ultrasonographic evidence of ovarian dysfunction, such as Polycystic Ovary
Syndrome (PCOS) or ovarian anomalies such as dermoid or hemorrhagic cysts;
Ultrasonographic evidence of uterine anomalies, including but not limited to
intramural or submucosal leiomyomas (fibroids) cysts, endometrial polyps, ASRM Class
I-VI uterine malformations or intrauterine fluid collections.

- Pregnancy (suspected or diagnosed) or lactation.

- Has had a prior partial or total hysterectomy or tubal ligation.

- Has had prior surgical procedures to the cervix (cryoablation, loop electrical
excision procedure [LEEP] or other similar procedures).

- Currently using an IUD for any reason.

- Potential volunteers who are at high risk of developing complications while taking
oral contraceptives will not be entered into the study in accordance with normal
standards of good clinical practice.

- History or suspicion of drug or alcohol abuse. Criteria Based Upon Medical Histories
For Cohorts 1, 2, 3

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- History of regular alcohol consumption within 6 months of the study defined as: An
average weekly intake of >7 drinks. One drink is equivalent to 12 grams of alcohol: 12
ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof
distilled spirits.

- 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.

- History of hypertension, use of an anti-hypertensive, or any systolic blood pressure
>=140 millimeter of mercury (mmHg) or diastolic blood pressure >=90 mmHg.

Criteria Based Upon Diagnostic Assessments For Cohorts 1, 2, 3

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- A posit


Age minimum: 18 Years
Age maximum: 35 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Embryo Transfer

Intervention(s)

Drug: Epelsiban

Drug: Ortho-Cylcen (21)® tablet

Drug: Placebo

Drug: Oxytocin

Primary Outcome(s)

Reduction in the frequency of subendometrial contractions in Cohorts 2 A, B and C, all during the periovulatory phase. [Time Frame: Up to Day 2]

Plasma concentrations of epelsiban or metabolite and the reduction of subendometrial contraction frequency in Cohorts 2 A, B and C, all during the periovulatory phase. [Time Frame: PK samples will be collected at 3, 3.25, 3.5, 4, 6.5, 11, 15, 27, 31 and 39 hours post dose in cohort 2.]

The effect of the infused oxytocin dose on the time course of the frequency of endometrial contractions in Cohort 1 during the periovulatory phase [Time Frame: Up to Day 3]

Frequency of endometrial contractions in Cohorts 2A, 2B and 2C during the periovulatory phase and 3-5 days post ovulation. [Time Frame: Up to Day 2]

The duration of the reduction in subendometrial contractions in Cohorts 2 A, B and C, all during the periovulatory phase [Time Frame: Up to Day 2]

Secondary Outcome(s)

Change from Baseline in laboratory parameters in Cohort 1 [Time Frame: Baseline (screening) and upto 21 days]

Change from Baseline in vital signs in Cohort 1 [Time Frame: Baseline (screening) and upto 21 days]

Frequency of subendometrial contractility in Cohort 3 [Time Frame: Up to Day 2]

Number of subjects with adverse events in Cohort 1 [Time Frame: 18 days]

Change from Baseline in ECG parameters in Cohort 3 [Time Frame: Baseline (screening) and upto 19 days]

Change from Baseline in electrocardiogram (ECG) parameters in Cohort 1 [Time Frame: Baseline (screening) and upto 21 days]

Composite of PK parameters following epelsiban dosing [Time Frame: PK samples will be collected at 3, 3.25, 3.5, 4, 6.5, 11, 15, 27, 31 and 39 hours post dose in cohort 2.]

Number of subjects with adverse events (AEs) in Cohort 2 [Time Frame: 17 days]

Change from Baseline in laboratory parameters in Cohort 2 [Time Frame: Baseline (screening) and upto 20 days]

Change from Baseline in laboratory parameters Cohort 3 [Time Frame: Baseline (screening) and upto 19 days]

Change from Baseline in ECG parameters in Cohort 2 [Time Frame: Baseline (screening) and upto 20 days]

Change from Baseline in vital signs in Cohort 2 [Time Frame: Baseline (screening) and upto 20 days]

Frequency of endometrial and subendometrial contractility in Cohort 2. [Time Frame: Up to Day 3]

Change from Baseline in vital signs in Cohort 3 [Time Frame: Baseline (screening) and upto 19 days]

Number of subjects with adverse events in Cohort 3 [Time Frame: 16 days]

Secondary ID(s)

116828

Source(s) of Monetary Support

Please refer to primary and secondary sponsors