Trial Outcomes & Findings for The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor (NCT NCT00404768)

Last Updated: 2018-01-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

Up to Follow-up (Week 12)

Results posted on

2018-01-16

Participant Flow

This study was conducted at multiple centers in the United States, United Kingdom, Singapore, France, Bulgaria, Spain, Argentina, South Korea, and Colombia from 03-December-2007 to 22-June-2011.

Participant milestones

Participant milestones
Measure	Part A/B: IV GSK221149A Eligible participants received a single intravenous (IV) infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 milligrams (mg) matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 nanogram/milliliter (ng/mL).	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Active (GSK221149A) Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a mean steady-state concentration (Css,ave) of 75 ng/mL.	Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Part A and B STARTED	20	9	0	0
Part A and B COMPLETED	19	8	0	0
Part A and B NOT COMPLETED	1	1	0	0
Part C STARTED	0	0	30	34
Part C COMPLETED	0	0	22	20
Part C NOT COMPLETED	0	0	8	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A/B: IV GSK221149A Eligible participants received a single intravenous (IV) infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 milligrams (mg) matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 nanogram/milliliter (ng/mL).	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Active (GSK221149A) Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a mean steady-state concentration (Css,ave) of 75 ng/mL.	Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Part A and B Withdrawn due to labor progression	1	0	0	0
Part A and B Withdrawn as delivery imminemnt	0	1	0	0
Part C Adverse Event	0	0	0	3
Part C Lost to Follow-up	0	0	3	1
Part C Withdrawal by Subject	0	0	2	1
Part C Early withdrawal from study medication	0	0	1	0
Part C Participant did not respond to therapy	0	0	1	1
Part C Physician withdrew the study medication	0	0	1	0
Part C Participant delivered baby	0	0	0	1
Part C Unsatisfactory uterine response to IP	0	0	0	1
Part C Active labor	0	0	0	1
Part C Lack of Efficacy	0	0	0	2
Part C Treatment failure	0	0	0	1
Part C Investigator discretion	0	0	0	1
Part C Researcher suspended study medication	0	0	0	1

Baseline Characteristics

The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.	Total n=93 Participants Total of all reporting groups
Age, Continuous	25.6 Years STANDARD_DEVIATION 4.97 • n=93 Participants	25.2 Years STANDARD_DEVIATION 5.86 • n=4 Participants	26.7 Years STANDARD_DEVIATION 5.66 • n=27 Participants	27.8 Years STANDARD_DEVIATION 6.26 • n=483 Participants	26.4 Years STANDARD_DEVIATION 5.84 • n=36 Participants
Sex: Female, Male Female	20 Participants n=93 Participants	30 Participants n=4 Participants	9 Participants n=27 Participants	34 Participants n=483 Participants	93 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	3 Participants n=36 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants	11 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	4 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	7 Participants n=36 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	23 Participants n=4 Participants	8 Participants n=27 Participants	24 Participants n=483 Participants	72 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Week 12)

Population: Safety Population which comprised of all participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With Vital Sign Values of Potential Clinical Concern High heart rate	2 Participants	4 Participants	0 Participants	3 Participants
Number of Participants With Vital Sign Values of Potential Clinical Concern Low diastolic blood pressure	1 Participants	4 Participants	0 Participants	4 Participants
Number of Participants With Vital Sign Values of Potential Clinical Concern High diastolic blood pressure	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Sign Values of Potential Clinical Concern Low systolic blood pressure	0 Participants	3 Participants	0 Participants	4 Participants
Number of Participants With Vital Sign Values of Potential Clinical Concern High systolic blood pressure	1 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Week 12)

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern	13 Participants	15 Participants	8 Participants	9 Participants

PRIMARY outcome

Timeframe: Up to 24 hours post-treatment

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern	10 Participants	22 Participants	7 Participants	28 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Week 12)

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	11 Participants	14 Participants	2 Participants	17 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	1 Participants	2 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 48 hours-post dose

Population: Pharmacodynamic Population which comprised of all participants who provided pharmacodynamic data. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Assessment of Amniotic Fluid Index (AFI) Pre-dose	17.21 Score Standard Deviation 6.213	11.86 Score Standard Deviation 3.707	16.88 Score Standard Deviation 4.295	13.34 Score Standard Deviation 3.955
Assessment of Amniotic Fluid Index (AFI) 12 Hours	18.34 Score Standard Deviation 5.208	—	12.98 Score Standard Deviation 5.509	—
Assessment of Amniotic Fluid Index (AFI) 24 Hours	—	13.15 Score Standard Deviation 3.860	—	12.71 Score Standard Deviation 4.662
Assessment of Amniotic Fluid Index (AFI) 48 Hours	—	13.38 Score Standard Deviation 4.551	—	12.72 Score Standard Deviation 4.379

PRIMARY outcome

Timeframe: Up to 48 hours post-dose

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=14 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=5 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B	9 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to 48 hours post-dose

Population: Pharmacodynamic Population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Fetal Heart Rate Monitoring up to 48 Hours Pre-dose	140.0 Beats per minute Standard Deviation 10.37	137.3 Beats per minute Standard Deviation 7.77	134.8 Beats per minute Standard Deviation 13.25	139.8 Beats per minute Standard Deviation 8.49
Fetal Heart Rate Monitoring up to 48 Hours 2 Hours	140.0 Beats per minute Standard Deviation 9.41	138.4 Beats per minute Standard Deviation 11.63	136.6 Beats per minute Standard Deviation 10.27	137.4 Beats per minute Standard Deviation 10.80
Fetal Heart Rate Monitoring up to 48 Hours 4 Hours	143.2 Beats per minute Standard Deviation 11.44	133.0 Beats per minute Standard Deviation 9.87	136.3 Beats per minute Standard Deviation 11.88	138.3 Beats per minute Standard Deviation 13.70
Fetal Heart Rate Monitoring up to 48 Hours 6 Hours	143.0 Beats per minute Standard Deviation 10.37	133.0 Beats per minute Standard Deviation 14.77	139.4 Beats per minute Standard Deviation 14.00	137.1 Beats per minute Standard Deviation 9.42
Fetal Heart Rate Monitoring up to 48 Hours 8 Hours	138.8 Beats per minute Standard Deviation 10.51	133.2 Beats per minute Standard Deviation 9.28	137.4 Beats per minute Standard Deviation 11.69	134.1 Beats per minute Standard Deviation 10.52
Fetal Heart Rate Monitoring up to 48 Hours 12 Hours	139.2 Beats per minute Standard Deviation 9.95	135.7 Beats per minute Standard Deviation 9.89	131.4 Beats per minute Standard Deviation 9.97	135.4 Beats per minute Standard Deviation 9.14
Fetal Heart Rate Monitoring up to 48 Hours 18 Hours	140.8 Beats per minute Standard Deviation 9.27	138.7 Beats per minute Standard Deviation 10.93	137.8 Beats per minute Standard Deviation 11.42	135.4 Beats per minute Standard Deviation 10.68
Fetal Heart Rate Monitoring up to 48 Hours 24 Hours	142.8 Beats per minute Standard Deviation 12.17	139.6 Beats per minute Standard Deviation 14.70	139.6 Beats per minute Standard Deviation 10.47	135.2 Beats per minute Standard Deviation 9.16
Fetal Heart Rate Monitoring up to 48 Hours 36 Hours	—	133.8 Beats per minute Standard Deviation 10.88	—	137.4 Beats per minute Standard Deviation 11.98
Fetal Heart Rate Monitoring up to 48 Hours 48 Hours	—	140.6 Beats per minute Standard Deviation 13.64	—	140.5 Beats per minute Standard Deviation 10.27

PRIMARY outcome

Timeframe: Up to 48 hours post-dose

Population: Pharmacodynamic Population.

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.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=14 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=5 Participants Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 Participants Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants Achieving Uterine Quiescence	9 Participants	18 Participants	2 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 48 hours post-dose

Population: Pharmacodynamic Population.

Preterm is defined as babies born alive before 37 weeks of pregnancy are completed. There are sub-categories of preterm birth, based on gestational age: extremely preterm (\<28 weeks) very preterm (28 to \<32 weeks). Number of participants with preterm births are presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants With Preterm Births in Part C	5 Participants	16 Participants	—	—

SECONDARY outcome

Timeframe: 1 minute and 5 minutes after birth

Population: Pharmacodynamic Population.

APGAR scores range from 0 to 2 for each condition (color, reflex response, muscle tone, respiration and heart rate) with a maximum final total score of 10. For heart rate: 0=no heart rate, 1=\<100 bpm (baby not very responsive), 2=\>100 bpm (baby vigorous); for respiration: 0=no breathing, 1= weak cry, 2=good, strong cry; for muscle tone: 0=limp, 1=some flexing of arms and legs, 2=active motion; for reflex response: 0=no response, grimace during stimulation, 2=grimace and cough or sneeze during stimulation; for color: 0=blue/pale, 1=good body color but blue hands and feet, 3=completely pink or good color. APGAR total score is the sum of sub-scores ranging from 0 to 10, where lower score indicates worst condition and higher score indicates best condition.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=9 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Apgar Scores in Part A and B APGAR Five Minute Score	8.8 Scores on a Scale Standard Deviation 0.72	9.0 Scores on a Scale Standard Deviation 0.00	—	—
Neonatal Apgar Scores in Part A and B APGAR One Minute Score	7.7 Scores on a Scale Standard Deviation 1.60	8.2 Scores on a Scale Standard Deviation 0.67	—	—

SECONDARY outcome

Timeframe: At birth and Follow-up (Week 12)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of weight gain. Weight gain was measured at birth and follow-up (Week 12). Mean weight gain is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=9 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Weight Gain in Part A and B At Birth	3233.81 Grams Standard Deviation 478.8	3090.33 Grams Standard Deviation 643.2	—	—
Neonatal Weight Gain in Part A and B At Follow-up	4548.02 Grams Standard Deviation 809.1	4710.29 Grams Standard Deviation 818.0	—	—

SECONDARY outcome

Timeframe: At Birth and Follow-up (Week 12)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of head circumference. Head circumference was measured at birth and follow-up (Week 12). Mean head circumference is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=9 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Head Circumference in Part A and B At Birth	34.145 Centimeters Standard Deviation 1.6187	35.903 Centimeters Standard Deviation 7.7959	—	—
Neonatal Head Circumference in Part A and B At Follow-up	37.921 Centimeters Standard Deviation 5.1082	36.667 Centimeters Standard Deviation 1.5000	—	—

SECONDARY outcome

Timeframe: At birth and follow-up (approximately 4 to 6 weeks of age)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of neonatal length. Neonatal length was measured at birth and follow-up (approximately 4 to 6 weeks of age). Mean Neonatal length is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=20 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=9 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Length Measured at 4-6 Weeks of Age in Part A and B At Birth	50.3 Centimeters Standard Deviation 3.18	48.7 Centimeters Standard Deviation 3.64	—	—
Neonatal Length Measured at 4-6 Weeks of Age in Part A and B At Follow-up	54.6 Centimeters Standard Deviation 3.03	53.1 Centimeters Standard Deviation 3.04	—	—

SECONDARY outcome

Timeframe: Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion

Population: Safety Population. Only those participants who received oral GSK221149A 125 mg were assessed for PK parameters.

Blood samples (approximately 2mL) were collected for the PK measurement of plasma GSK221149 at pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=8 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Derived Plasma GSK221149 Pharmacokinetic Parameters- Area Under Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) and Area Under Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC [0 to Last]) AUC infinity	429.73 Nanogram*hour per milliliter Geometric Coefficient of Variation 40.1	—	—	—
Derived Plasma GSK221149 Pharmacokinetic Parameters- Area Under Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) and Area Under Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC [0 to Last]) AUC last	419.09 Nanogram*hour per milliliter Geometric Coefficient of Variation 41.7	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion

Population: Safety Population. Only those participants who received oral GSK221149A 125 mg were assessed for PK parameters

Blood samples (approximately 2 mL) were collected for the PK measurement of plasma GSK221149 at pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=8 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Derived Plasma GSK221149 Pharmacokinetic Parameters- Observed Elimination Half-life (T-half) and Time to Maximum Observed Drug Concentration (T-max) T-half	1.534 Hours Standard Deviation 0.6052	—	—	—
Derived Plasma GSK221149 Pharmacokinetic Parameters- Observed Elimination Half-life (T-half) and Time to Maximum Observed Drug Concentration (T-max) T-max	1.713 Hours Standard Deviation 0.8286	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion

Population: Safety Population. Only those participants who received oral GSK221149A 125 mg were assessed for PK parameters.

Blood samples (approximately 2 mL) were collected for the PK measurement of plasma GSK221149 at pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=8 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Derived Plasma GSK221149 Pharmacokinetic Parameters- Maximum Plasma Concentration (Cmax)	126.93 Nanogram per milliliter Geometric Coefficient of Variation 66.4	—	—	—

SECONDARY outcome

Timeframe: 1 minute and 5 minute after birth at 4 to 12 weeks post adjusted gestational age

Population: Pharmacodynamic Population.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C APGAR Five Minute Score	9.0 Scores on a scale Standard Deviation 0.53	8.9 Scores on a scale Standard Deviation 0.34	—	—
Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C APGAR One Minute Score	8.3 Scores on a scale Standard Deviation 0.88	8.2 Scores on a scale Standard Deviation 0.77	—	—

SECONDARY outcome

Timeframe: At birth and Follow-up (Week 12)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of weight gain. Weight gain was measured at birth and follow-up (Week 12). Mean weight gain is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Birth	3098.63 Grams Standard Deviation 512.644	2940.03 Grams Standard Deviation 584.950	—	—
Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Follow-up	3427.14 Grams Standard Deviation 635.5	3601.79 Grams Standard Deviation 659.479	—	—

SECONDARY outcome

Timeframe: At Birth and Follow-up (Week 12)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of head circumference. Head circumference was measured at birth and follow-up (Week 12). Mean head circumference is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Birth	33.319 Centimeteres Standard Deviation 1.7882	33.080 Centimeteres Standard Deviation 1.6374	—	—
Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Follow-up	35.057 Centimeteres Standard Deviation 1.7581	35.160 Centimeteres Standard Deviation 1.7792	—	—

SECONDARY outcome

Timeframe: At Birth and Follow-up (Week 12)

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Neonatal safety was assessed through assessment of neonatal length. Neonatal length was measured at birth and follow-up (Week 12). Mean neonatal length is presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Birth	47.8 Centimeters Standard Deviation 2.78	47.8 Centimeters Standard Deviation 3.39	—	—
Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C At Follow-up	50.6 Centimeters Standard Deviation 2.89	51.3 Centimeters Standard Deviation 3.30	—	—

SECONDARY outcome

Timeframe: 48 hours post-dose

Population: Pharmacodynamic Population.

Tocolytics are medications used to suppress premature labor. They are given when delivery would result in premature birth. Number of participants who remained undelivered without rescue tocolytic therapy after 48 hours are presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C	30 Participants	34 Participants	—	—

SECONDARY outcome

Timeframe: First 6 hours of therapy

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

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. Baseline was Day 0. Reduction from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percentage reduction from Baseline in number of uterine contractions \[\>30 sec\] per hour within first 6 hours of therapy are presented.

Outcome measures

Outcome measures
Measure	Part A/B: IV GSK221149A n=30 Participants Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=34 Participants Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 1 Hour	-26.29 Percent change Standard Deviation 45.406	-19.03 Percent change Standard Deviation 41.345	—	—
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 2 Hour	-36.65 Percent change Standard Deviation 44.144	-27.67 Percent change Standard Deviation 58.181	—	—
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 3 Hour	-49.14 Percent change Standard Deviation 42.200	-23.11 Percent change Standard Deviation 68.820	—	—
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 4 Hour	-62.06 Percent change Standard Deviation 38.874	-35.56 Percent change Standard Deviation 69.171	—	—
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 5 Hour	-59.20 Percent change Standard Deviation 43.290	-51.78 Percent change Standard Deviation 49.544	—	—
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C 6 Hour	-65.32 Percent change Standard Deviation 37.762	-49.26 Percent change Standard Deviation 47.871	—	—

Adverse Events

Part A/B: IV GSK221149A

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Part C: Active (GSK221149A)

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Part A/B: Oral GSK221149A

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part C: Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Part A/B: IV GSK221149A n=20 participants at risk Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 participants at risk Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 participants at risk Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 participants at risk Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Pregnancy, puerperium and perinatal conditions Postpartum haemorrhage	5.0% 1/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Retained placenta or membranes	5.0% 1/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Investigations Amniotic fluid volume decreased	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Vascular disorders Hypertension	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Metabolism and nutrition disorders Hypoglycaemia neonatal	5.0% 1/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Metabolism and nutrition disorders Malnutrition	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Hepatobiliary disorders Hyperbilirubinaemia neonatal	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Jaundice neonatal	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Meconium in amniotic fluid	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Respiratory, thoracic and mediastinal disorders Apnoea	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Respiratory, thoracic and mediastinal disorders Neonatal respiratory distress syndrome	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Respiratory, thoracic and mediastinal disorders Neonatal tachypnoea	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Congenital, familial and genetic disorders Cerebral atrophy congenital	5.0% 1/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Congenital, familial and genetic disorders Heart disease congenital	5.0% 1/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.

Measure	Part A/B: IV GSK221149A n=20 participants at risk Eligible participants received a single IV infusion of GSK221149A over 12 hours followed by a single oral dose of placebo tablets of strength 125 mg matched to GSK221149A. The GSK221149 loading dose and infusion rate were increased in a stepwise fashion every 3 hours to achieve plasma concentrations of 10, 30, 75, and 150 ng/mL.	Part C: Active (GSK221149A) n=30 participants at risk Each participant received a loading dose of 6 mg GSK221149A over 5 minutes, followed by a constant IV infusion of 6 mg/h GSK221149A over 48 hours to reach a Css,ave of 75 ng/mL.	Part A/B: Oral GSK221149A n=9 participants at risk Eligible participants received placebo IV infusion over 12 hours followed by a single oral dose of GSK221149 125 mg tablets. The placebo loading dose and infusion rate were also increased every 3 hours in a stepwise fashion.	Part C: Placebo n=34 participants at risk Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours.
Nervous system disorders Headache	10.0% 2/20 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	13.3% 4/30 • Number of events 4 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Gastrointestinal disorders Dyspepsia	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	10.0% 3/30 • Number of events 3 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Labour pain	20.0% 4/20 • Number of events 4 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Hepatobiliary disorders Hyperbilirubinaemia neonatal	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	8.8% 3/34 • Number of events 3 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Gastrointestinal disorders Nausea	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	6.7% 2/30 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Gastrointestinal disorders Abdominal pain upper	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Musculoskeletal and connective tissue disorders Back pain	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	6.7% 2/30 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	3.3% 1/30 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Blood and lymphatic system disorders Anaemia neonatal	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Blood and lymphatic system disorders Anaemia of pregnancy	10.0% 2/20 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Jaundice neonatal	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	2.9% 1/34 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Nervous system disorders Paraesthesia	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Pregnancy, puerperium and perinatal conditions Polyhydramnios	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Psychiatric disorders Postpartum depression	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	5.9% 2/34 • Number of events 2 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Infections and infestations Urinary tract infection	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	11.1% 1/9 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Investigations Blood phosphorus decreased	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	11.1% 1/9 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
General disorders Developmental delay	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Nervous system disorders Dysgeusia	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
General disorders Feeling hot	0.00% 0/20 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	11.1% 1/9 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
General disorders Infusion site irritation	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
General disorders Injection site pain	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Congenital, familial and genetic disorders Macrocephaly	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Infections and infestations Neonatal pneumonia	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Injury, poisoning and procedural complications Procedural pain	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Infections and infestations Proteus infection	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Renal and urinary disorders Renal impairment neonatal	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Infections and infestations Staphylococcal infection	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Respiratory, thoracic and mediastinal disorders Transient tachypnoea of the newborn	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Renal and urinary disorders Ureteral disorder	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.
Infections and infestations Urinary tract infection neonatal	5.0% 1/20 • Number of events 1 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/30 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/9 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.	0.00% 0/34 • Up to Follow-up (Week 12) Safety Population was used for adverse events assessment.