Obstetric Labour, Premature
Conditions
Keywords
Preterm labor, Retosiban, Pharmacokinetics, Safety, Infusion, GSK2847065
Brief summary
This study in healthy, adult Japanese women will characterize the PK, safety and tolerability of retosiban at the therapeutic doses planned to be evaluated in Phase 3. The PK data will be compared to a sub-set of Caucasian women given the same dose of retosiban. This study has two cohorts, cohort 1 will be a double-blind sponsor-open (subjects and investigator blinded and sponsor unblinded), randomized, continuous 48 hours (h) infusion study in healthy, adult Japanese women of child-bearing potential. Cohort 2 is an open label and continuous retosiban 48 h infusion study in Caucasian, adult, healthy women of child bearing potential. So, the PK can be compared with those of Japanese women. Approximately 32 subjects will be enrolled. In cohort 1, approximately 24 subjects will be enrolled and randomized to retosiban and placebo (2:1 ratio) to have 18 women with 12 active, 6 placebo completed subjects. In Cohort 2, 8 subjects will be enrolled to have 6 competed subjects. The total duration of a subject's involvement in this part is anticipated to be up to 6 weeks (including the 28 day screening period).
Interventions
DRUGRetosiban solution for Infusion
Retosiban will be supplied as clear, colorless IV solution for infusion in 5 mL vial with a unit dose strength of 15 milligrams per milliliter (mg/mL) (each 5 mL vial contains 75 mg retosiban), dosed at up to 300 mg over 48 h infusion
DRUGPlacebo
Placebo will be supplied as a clear, colorless IV solution for infusion with a unit dose strength of 0.9% sodium chloride (NaCl) normal saline
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who are between 20 and 45 years and of age, inclusive at the time of signing the informed consent form. * Japanese, defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese, and that lifestyle including diet has not changed significantly since leaving Japan. Japanese subjects should also have lived outside Japan for less than 10 years. * Caucasian subjects as defined as an individual having four grandparents who are all descendants of the original peoples of Europe. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring obtained at the screening visit. * 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 medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=43 kilograms (kg) and body mass index (BMI) within the range 17-29.9 kilogram per square meter (kg/m\^2) (inclusive). * Female subjects- A female subject is eligible to participate if she is: A female of non-productive potential secondary to a personal history of a hysterectomy or tubal sterilization procedure. A female of reproductive potential who is not pregnant (as confirmed by a negative urine or serum human chorionic gonadotropin \[hCG\] test), not lactating, and agrees to follow one of the options listed in protocol. Contraception requirement for female subjects from 28 days prior to the first dose of study treatment and until completion of the follow-up visit. * Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of PK parameters of retosiban administered by intravenous infusion to healthy adult Japanese and Caucasian women of child-bearing potential: AUC, Cmax, t1/2 and clearance of retosiban | Pre-dose, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 18 h, 24 h (just before dose increase), 24.5 h, 25 h, 26 h, 28 h, 36 h, 42 h, 48 h, 48.5 h, 49 h, 50 h, 52 h, 54 h, 56 h and 60 h post start of the infusion | PK parameters will include: area under concentration-time curve (AUC), maximum observed concentration (Cmax), terminal phase half-life (t1/2) and clearance (CL) of retosiban |
| Composite of PK parameters of retosiban and its major inactive metabolite (GSK2847065) in healthy adult Japanese and Caucasian women of child-bearing potential: AUC, Cmax, t1/2 | Pre-dose, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 18 h, 24 h (just before dose increase), 24.5 h, 25 h, 26 h, 28 h, 36 h, 42 h, 48 h, 48.5 h, 49 h, 50 h, 52 h, 54 h, 56 h and 60 h post start of the infusion | AUC, Cmax, t1/2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vital sign assessment as a measure of safety | Up to 13 days | Vital signs will be measured in semi-supine position after 5 minutes rest and will include body temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate |
| Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | Up to 13 days | AEs and SAEs will be collected from the start of study treatment until the follow-up contact |
| Concomitant medication assessment as a measure of safety | Up to 13 days | — |
| Safety as assessed by electrocardiogram (ECG) | Up to 13 days | Triplicate 12-lead ECGs will be obtained at each time point during the study |
| Composite of clinical laboratory assessments | Up to 13 days | Clinical laboratory tests will include hematology, clinical chemistry, urinalysis and additional parameters |
Countries
United States
Outcome results
None listed