A Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK221149A Administered Intravenously and to Investigate the Pharmacokinetics of GSK221149A Administered Orally to Healthy, Pregnant Females With Uncomplicated Pre-term Labor Between 300/7 and 356/7 Weeks' Gestation

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

时间窗: Up to Follow-up (Week 12)

An AE is defined as 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. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact.

Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern

时间窗: Up to 24 hours post-treatment

Hematology parameters included complete blood count with red blood cell indices and white blood cell differential, platelet count, human immune deficiency virus, Hepatitis C antibody and Hepatitis B surface antigen. Clinical chemistry parameters included blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, phosphate, chloride, total CO2, calcium, aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyltransferase (GGT), alkaline phosphatase, total bilirubin, uric acid, albumin and total protein. Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with clinical chemistry and hematology parameter values of potential clinical concern are presented.

Number of Participants With Vital Sign Values of Potential Clinical Concern

时间窗: Up to Follow-up (Week 12)

Vital signs included blood pressure (systolic and diastolic) and heart rate. Maternal blood pressure and heart rate were measured with the participant in the semi-supine position. Blood pressure was measured in millimeters of mercury (mmHg) and heart rate in beats per minute (bpm). Potential clinical concern range for systolic blood pressure: \<85 and \>160 mmHg, for diastolic: \<45 and \>100 mmHg and heart rate: \<40 and \>110 bpm. Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with vital sign values of potential clinical concern are presented.

Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern

时间窗: Up to Follow-up (Week 12)

All scheduled 12-lead ECGs were obtained after the participant was rested in the semi-supine position for approximately 15 minutes. Whenever 12-lead ECGs were performed at the same nominal time as a blood draw or blood pressure and pulse rate measurement, the 12-lead ECG were obtained first. ECGs were repeated or recorded in triplicate and the average value recorded at the investigators discretion. The potential clinical concern range for ECG parameters were: Absolute QT corrected (QTc) interval: \>450 milliseconds (msec), Increase from Baseline (Day 0): QTc \>60 msec, PR interval: \<110 and \>220 msec and QRS interval: \<75 and \>110 msec. All 12-lead ECGs obtained throughout the study day were evaluated for safety and were reviewed by the investigator or investigator designee. Number of participants with electrocardiogram values of potential clinical concern are presented.

Number of Participants Achieving Uterine Quiescence

时间窗: Up to 48 hours post-dose

Uterine quiescence was defined as 4 contractions per/hour or less with no cervical change within the first 6 hours of therapy. Number of participants (from part A,B,C) achieving uterine Quiescence are presented.

Fetal Heart Rate Monitoring up to 48 Hours

时间窗: Up to 48 hours post-dose

Fetal heart rate monitoring was incorporated to assess fetal tolerability. Fetal heart rate was monitored continuously at 2, 4, 6, 8, 12, 18, 24, 36 and up to 48 hours post-therapy. Mean fetal heart rate is presented. Data for only key-time points values have been presented.

Assessment of Amniotic Fluid Index (AFI)

时间窗: Up to 48 hours-post dose

AFI is a quantitative estimate of amniotic fluid and an indicator of fetal well-being. AFI is the score (expressed in centimetes) given to the amount of amniotic fluid seen on ultrasonography of a pregnant uterus. An AFI between 8 to 18 is considered normal. An AFI \< 5 to 6 is considered as oligohydramnios characterized by deficiency of amniotic fluid. An AFI \> 18 to 24 is considered as polyhydramnios characterized by excess of amniotic fluid in the amniotic sac.

Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B

时间窗: Up to 48 hours post-dose

For uterine contraction assessment, an external tocodynamometer was fastened around the participant's abdomen. The number and duration of contraction was recorded at screening and up to 48 hours post-dose.The number of participants that achieve a reduction of at least 50% in uterine contractions with no cervical change within 6 hours and to maintain that reduction until 12 hours of therapy has been presented.