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.

Conditions: Pre-term labor
MedDRA version: 9.1Level: LLTClassification code 10023555Term: Labour premature

Registration Number: EUCTR2006-005807-32-BG

Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary: Not available

Detailed Description: Not available

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 to 45 years of age inclusive
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 =1 cm to <= 4 cm. 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
6. Ability to understand and provide written informed consent to participate in this study.
7. Women with gestational diabetes diagnosed during current pregnancy and controlled by diet and exercise will be permitted into the study. Women must have a non-fasting glucose at screening between 70mg/mL and 130 mg/mL by point-of-care dlucomer or between 70mg/mL and 140mg/mL by local laboratory determination to be enrolled in the study.
8. Women previously administered tocolytic treatment, which has been discintinued by the investigator for lack of efficacy or intolerance, do not require a 24-hour washout period if otherwise eligible for the study.
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. Patients who have received a cervical cerclage currently or in a previous pregnancy.
3. Patients who have received amniocentesis during the third trimester. Patients who have received a first and second trimester amniocentesis are allowed in the study if the results are normel.
4. 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)
5. Women with gestational diabetes requiring insulin or pre-existing diabetes mellitus are excluded. Use of oral antidiabetis agents for gestational diabetes is also exclusionary.
6. Known fetal intrauterine growth restriction or fetal congenital anomaly
7. Abnormal modified biophysical profile (NST is non-reactive and AFI <5)
8. Participation in another interventional (i.e any study involving an investigational
product or device) clinical trial during the current pregnancy. Women enrolled in an observational, non-interventional, non-device trial will be permitted into the study.
9. 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)
10. History of anaphylaxis or anaphylactoid reactions, or severe allergic responses to
drugs
11. Known to be positive for hepatitis C antibody, hepatitis B surface antigen or HIV on prenatal laboratory results
12. Use of prescription drugs that are potent CYP3A4 inhibitors, within 7 days or 5 halflives (whichever is longer) prior to first dose of medication.
13. 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
14. Consumption of grapefruit or grapefruit juice within 3 days prior to first dose of
medication
15. 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.)
16. QTc > 480 msec for patients with Bundle Branch Block
17. Use of illicit drugs or positive urine drug screen during pregnancy
18. Any contraindication to tocolytic therapy, including (but not limited to) suspected
intrauterine infection, vaginal bleeding, pre-eclampsia/eclampsia
19. Trauma within 48 hours of presentation in preterm labor
20. Subjects previously enrolled in study OTA105256
21. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with exception of Gilbert's syndrome or asymptomatic gallstones)