Embryo TransferPhase 1NCT02257359
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Epelsiban in Healthy Female Volunteers
A Phase 1 study testing Epelsiban in people with Embryo Transfer, run by GlaxoSmithKline at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Embryo Transfer
- What is being tested?
- Epelsiban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2014to 29 Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Overland Park, Kansas, 66211
About this study
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
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.
- Conditions
- Embryo Transfer
- Being tested
- Epelsiban
- Keywords
- Epelsiban, Healthy Female Volunteers, Safety, Tolerability, Oxytocin, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpelsibanDrug
Epelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet.
| Study group | Role | What they receive |
|---|---|---|
| Epelsiban Cohort 1 | Experimental | Subjects will receive 300 mg of epelsiban administered orally twice (every 12 hr) on Day 1 (total daily dose of 600 mg) Receives: Drug: Epelsiban |
| Epelsiban Cohort 2 | Experimental | 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). Receives: Drug: Epelsiban |
| Additional Cohorts TBD (to be decided) | Experimental | Subjects will be enrolled if determined necessary, based on data collected in Epelsiban Cohort 1 and Cohort 2 Receives: Drug: Epelsiban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite pharmacokinetic parameters of epelsiban and its metabolite (GSK2395448)
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).
Measured: Up to Day 2
Number of subjects with Adverse events (AEs)
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.
Measured: Up to Day 12
Assessment of clinical observations
Measured: Up to Day 12
Assessment of hematology parameters
Hematology parameters include complete blood count with red blood cell indices, white blood cell count differential, hemoglobin, hematocrit and platelet count.
Measured: Up to Day 12
Assessment of clinical chemistry parameters
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.
Measured: Up to Day 12
Assessment of urinalysis by dipstick
Urinalysis includes specific gravity, pH, glucose, protein, blood and ketones by dipstick. If blood or protein is abnormal microscopic examination will be done.
Measured: Up to Day 12
Assessment of vital sign measurements
Vital sign measurements will include temperature, systolic and diastolic blood pressure and heart rate.
Measured: Up to Day 12
Assessment of 12-lead electrocardiogram (ECG)
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.
Measured: Up to Day 12
Assessment of physical examination findings
A physical examination will include, at a minimum, assessment of the cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight will also be measured
Measured: Up to Day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2014 (estimated)
- Study start18 Dec 2014
- Primary completion29 Jan 2015
- Study completion29 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Embryo TransferStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02257359
- Sponsor's protocol ID
- 201691
- Status last verified
- Sep 2018
- First submitted
- 2 Oct 2014
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
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.
PubMed 28556598
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02257359
- Acronym / sponsor ID
- 201691
- Conditions
- Embryo Transfer
- Keywords
- Epelsiban, Healthy Female Volunteers, Safety, Tolerability, Oxytocin, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2014 (actual)
- Primary completion
- 29 Jan 2015 (actual)
- Study completion
- 29 Jan 2015 (actual)
- First posted
- 6 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Epelsiban Cohort 1 | Experimental | Drug: EpelsibanSubjects will receive 300 mg of epelsiban administered orally twice (every 12 hr) on Day 1 (total daily dose of 600 mg) |
| Epelsiban Cohort 2 | Experimental | Drug: EpelsibanEpelsiban 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). |
| Additional Cohorts TBD (to be decided) | Experimental | Drug: EpelsibanSubjects will be enrolled if determined necessary, based on data collected in Epelsiban Cohort 1 and Cohort 2 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpelsibanEpelsiban will be supplied as a 25 mg white to off-white round direct compression oral tablet. | Drug | Additional Cohorts TBD (to be decided), Epelsiban Cohort 1, Epelsiban Cohort 2 |
Primary outcome
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).
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.
Assessment of clinical observations
Time frame: 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.
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.
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.
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.
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.
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Derived from this study: PubMed 28556598Mahar 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.
- Results for study 201691 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
Related trials for Embryo Transfer
Not yet recruiting
Cryopreserved Pre-embryo Transfer in a Cytokine-rich Medium Versus Hyaluronic Acid
Frozen Embryo Transfer (FET)
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruitingObservational study
Linzagolix in Adenomyosis and Recurrent Implantation Failure
Adenomyosis of Uterus, Implantation Failure
RecruitingPhase 2
Effect of FB301 on Vaginal Bacterial Profile in Women With Asymptomatic Vaginal Dysbiosis Undergoing a Mock Frozen Embryo Transfer Cycle
Vaginal Dysbiosis
RecruitingPhase 2/3
Thymosin-α1 for Recurrent Implantation Failure
Recurrent Implantation Faliure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Epelsiban in people with Embryo Transfer, run by GlaxoSmithKline at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite pharmacokinetic parameters of epelsiban and its metabolite (GSK2395448) (time frame: Up to Day 2). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02257359, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.