A randomized, double-blind, placebo-controlled, dose ranging study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK221149A administered intravenously and the pharmacokinetics of GSK221149A administered orally in healthy, pregnant females, with uncomplicated pre-term labor between 30 0/7 ? 35 6/7 weeks gestation.Estudio aleatorizado, doble ciego, controlado con placebo, de rango de dosis para investigar la seguridad, tolerabilidad, farmacocinética y farmacodinamia de GSK221149A administrado por vía intravenosa y la farmacocinética de GSK221149A administrado por vía oral en mujeres embarazadas, sanas, con amenaza de parto pretérmino no complicado de 30 0/7 - 35 6/7 semanas de edad gestacional.

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 90

Inclusion Criteria

Part A and Part B
1. At least 18 years of age
2. 34 0/7 -35 6/7 weeks (best obstetric estimate, preferably first trimester ultrasound) with singleton pregnancy
3. Symptoms of pre-term labor: ?6 uterine contractions per hour, each of at least 30 sec in duration as measured by tocodynamometry, with cervical dilatation ?3cm
4. Intact fetal membranes
Part C
1. At least 18 years of age
2. 30 0/7 -35 6/7 weeks (best obstetric estimate, preferably first trimester ultrasound) with singleton pregnancy
3. Symptoms of pre-term labor: contractions at a frequency of 4 per 30 min or 6 per
hour, each of at least 30 sec in duration and confirmed by tocodynamometry
4. Cervical dilatation ?2 cm or a definitive cervical change from baseline assessment.
Subjects can not exceed a maximum cervical dilation of 4 cm to be included in this
study at the time of screening.
5. Intact fetal membranes
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any clinically relevant abnormality identified on the screening examination or any
other medical condition or circumstance making the patient (mother and/or fetus)
unsuitable for participation in the study
2. Any clinically relevant pre-existing or pregnancy-related co-morbid condition that
may affect maternal pregnancy outcome or neonatal outcome (eg. hypertension,
diabetes mellitus, bleeding/clotting diathesis)
3. Known fetal intrauterine growth restriction or fetal congenital anomaly
4. Abnormal modified biophysical profile (NST is non-reactive and AFI <5)
5. Participation in another interventional (i.e any study involving an investigational
product or device) clinical trial during the current pregnancy
6. Abuse of alcohol, defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units. One unit is equivalent to a half-pint
(220mL) of beer or 1 (25mL) measure of spirits, or 1 glass (125mL of wine)
7. History of anaphylaxis or anaphylactoid reactions, or severe allergic responses to
drugs
8. Known to be positive for hepatitis C antibody, hepatitis B surface antigen or HIV on prenatal laboratory results
9. Use of prescription drugs that are potent CYP3A4 inhibitors, within 7 days or 5 halflives (whichever is longer) prior to first dose of medication. Tocolytics are prohibited within 6 hours of enrolment
10. Use of dietary/herbal supplements including (but not limited to) St. John's wort,
kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, ginseng,
and red yeast rice (2-fold greater than the recommended daily allowance of 1200 mg
per day) within 7 days prior to first dose of medication
11. Consumption of grapefruit or grapefruit juice within 3 days prior to first dose of
medication
12. QTc > 450 msec (either QTcb or QTcf, machine or manual overread, on single or
average QTc value of triplicate ECGs obtained over a brief recording period.)
13. QTc > 480 msec for patients with Bundle Branch Block
14. Use of illicit drugs or positive urine drug screen during pregnancy
15. Any tocolytic therapy within 24 hours
16. Any contraindication to tocolytic therapy, including (but not limited to) suspected
intrauterine infection, vaginal bleeding, pre-eclampsia/eclampsia
17. Trauma within 48 hours of presentation in preterm labor
18. Subjects treated with dexamethasone