Obstetric Labour, Premature
Conditions
Keywords
Premature Labor, Pre Term Labor, intravenous, fetal fibronectin
Brief summary
Pre-Term Labor (prior to 37 weeks gestation) is the largest single cause of infant morbidity and mortality and is frequently associated with long-term disability. Oxytocin is a hormone produced by the body during labor. GSK221149A is an experimental drug that will be used to block the effects of oxytocin, and therefore pause or prevent contractions. In this study, patients with preterm labor will be given an intravenous infusion of GSK221149A over approximately 12 hours followed by an oral tablet in Parts A and B. In part C of this study, patients with preterm labor will be give an intravenous infusion of GSK221149A over approximately 48 hours. The use of a rescue tocolytic is allowed in the study.
Detailed description
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
Interventions
DRUGGSK221149A
6mg/h and 12 mg/h
DRUGPlacebo
Matched Placebo to Drug
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Healthy pregnant females, 30 -36 weeks pregnant, without ruptured membranes * 18-45 inclusive * Symptoms of pre-term labor, (greater than or equal to 6 uterine contractions per hour, each of which at least 30 sec in duration, with cervical dilatation of less than or equal to 4 cm, (measured by tocodynamometry).
Exclusion criteria
* 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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Vital Sign Values of Potential Clinical Concern | 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. |
| Assessment of Amniotic Fluid Index (AFI) | 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 Electrocardiogram (ECG) Values of Potential Clinical Concern | 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 With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern | 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 Adverse Events (AE) and Serious Adverse Events (SAE) | 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 50% Reduction in Uterine Contractions Per Hour in Part A and B | 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. |
| Fetal Heart Rate Monitoring up to 48 Hours | 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. |
| Number of Participants Achieving Uterine Quiescence | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | 1 minute and 5 minute after birth at 4 to 12 weeks post adjusted gestational age | 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. |
| Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At birth and Follow-up (Week 12) | 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. |
| Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth and Follow-up (Week 12) | 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. |
| Number of Participants With Preterm Births in Part C | Up to 48 hours post-dose | 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. |
| Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C | 48 hours post-dose | 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. |
| Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | First 6 hours of therapy | 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. |
| Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth and Follow-up (Week 12) | 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. |
| Neonatal Apgar Scores in Part A and B | 1 minute and 5 minutes after birth | 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. |
| Neonatal Weight Gain in Part A and B | At birth and Follow-up (Week 12) | 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. |
| Neonatal Head Circumference in Part A and B | At Birth and Follow-up (Week 12) | 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. |
| Neonatal Length Measured at 4-6 Weeks of Age in Part A and B | At birth and follow-up (approximately 4 to 6 weeks of age) | 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. |
| 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]) | Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion | 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. |
| Derived Plasma GSK221149 Pharmacokinetic Parameters- Observed Elimination Half-life (T-half) and Time to Maximum Observed Drug Concentration (T-max) | Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion | 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. |
| Derived Plasma GSK221149 Pharmacokinetic Parameters- Maximum Plasma Concentration (Cmax) | Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion | 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. |
Countries
Argentina, Bulgaria, Colombia, France, Lithuania, Puerto Rico, Singapore, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part A/B: IV GSK221149A 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. | 20 |
| 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. | 30 |
| 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. | 9 |
| Placebo Each participant received a loading dose of placebo over 5 minutes, followed by a constant IV infusion of placebo over 48 hours. | 34 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part A and B | Withdrawn as delivery imminemnt | 0 | 1 | 0 | 0 |
| Part A and B | Withdrawn due to labor progression | 1 | 0 | 0 | 0 |
| Part C | Active labor | 0 | 0 | 0 | 1 |
| Part C | Adverse Event | 0 | 0 | 0 | 3 |
| Part C | Early withdrawal from study medication | 0 | 0 | 1 | 0 |
| Part C | Investigator discretion | 0 | 0 | 0 | 1 |
| Part C | Lack of Efficacy | 0 | 0 | 0 | 2 |
| Part C | Lost to Follow-up | 0 | 0 | 3 | 1 |
| Part C | Participant delivered baby | 0 | 0 | 0 | 1 |
| 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 | Researcher suspended study medication | 0 | 0 | 0 | 1 |
| Part C | Treatment failure | 0 | 0 | 0 | 1 |
| Part C | Unsatisfactory uterine response to IP | 0 | 0 | 0 | 1 |
| Part C | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Part A/B: IV GSK221149A | Total | Placebo | Part A/B: Oral GSK221149A | Active (GSK221149A) |
|---|---|---|---|---|---|
| Age, Continuous | 25.6 Years STANDARD_DEVIATION 4.97 | 26.4 Years STANDARD_DEVIATION 5.84 | 27.8 Years STANDARD_DEVIATION 6.26 | 26.7 Years STANDARD_DEVIATION 5.66 | 25.2 Years STANDARD_DEVIATION 5.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 11 Participants | 6 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 7 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 72 Participants | 24 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Female | 20 Participants | 93 Participants | 34 Participants | 9 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 30 | 0 / 9 | 0 / 34 |
| other Total, other adverse events | 12 / 20 | 10 / 30 | 3 / 9 | 14 / 34 |
| serious Total, serious adverse events | 1 / 20 | 2 / 30 | 0 / 9 | 2 / 34 |
Outcome results
Primary
Assessment of Amniotic Fluid Index (AFI)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Assessment of Amniotic Fluid Index (AFI) | Pre-dose | 17.21 Score | Standard Deviation 6.213 |
| Part A/B: IV GSK221149A | Assessment of Amniotic Fluid Index (AFI) | 12 Hours | 18.34 Score | Standard Deviation 5.208 |
| Part C: Active (GSK221149A) | Assessment of Amniotic Fluid Index (AFI) | 24 Hours | 13.15 Score | Standard Deviation 3.86 |
| Part C: Active (GSK221149A) | Assessment of Amniotic Fluid Index (AFI) | Pre-dose | 11.86 Score | Standard Deviation 3.707 |
| Part C: Active (GSK221149A) | Assessment of Amniotic Fluid Index (AFI) | 48 Hours | 13.38 Score | Standard Deviation 4.551 |
| Part A/B: Oral GSK221149A | Assessment of Amniotic Fluid Index (AFI) | 12 Hours | 12.98 Score | Standard Deviation 5.509 |
| Part A/B: Oral GSK221149A | Assessment of Amniotic Fluid Index (AFI) | Pre-dose | 16.88 Score | Standard Deviation 4.295 |
| Part C: Placebo | Assessment of Amniotic Fluid Index (AFI) | 24 Hours | 12.71 Score | Standard Deviation 4.662 |
| Part C: Placebo | Assessment of Amniotic Fluid Index (AFI) | Pre-dose | 13.34 Score | Standard Deviation 3.955 |
| Part C: Placebo | Assessment of Amniotic Fluid Index (AFI) | 48 Hours | 12.72 Score | Standard Deviation 4.379 |
Primary
Fetal Heart Rate Monitoring up to 48 Hours
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 18 Hours | 140.8 Beats per minute | Standard Deviation 9.27 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 8 Hours | 138.8 Beats per minute | Standard Deviation 10.51 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | Pre-dose | 140.0 Beats per minute | Standard Deviation 10.37 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 24 Hours | 142.8 Beats per minute | Standard Deviation 12.17 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 4 Hours | 143.2 Beats per minute | Standard Deviation 11.44 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 6 Hours | 143.0 Beats per minute | Standard Deviation 10.37 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 2 Hours | 140.0 Beats per minute | Standard Deviation 9.41 |
| Part A/B: IV GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 12 Hours | 139.2 Beats per minute | Standard Deviation 9.95 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 18 Hours | 138.7 Beats per minute | Standard Deviation 10.93 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 8 Hours | 133.2 Beats per minute | Standard Deviation 9.28 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 24 Hours | 139.6 Beats per minute | Standard Deviation 14.7 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 36 Hours | 133.8 Beats per minute | Standard Deviation 10.88 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 48 Hours | 140.6 Beats per minute | Standard Deviation 13.64 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 6 Hours | 133.0 Beats per minute | Standard Deviation 14.77 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | Pre-dose | 137.3 Beats per minute | Standard Deviation 7.77 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 2 Hours | 138.4 Beats per minute | Standard Deviation 11.63 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 4 Hours | 133.0 Beats per minute | Standard Deviation 9.87 |
| Part C: Active (GSK221149A) | Fetal Heart Rate Monitoring up to 48 Hours | 12 Hours | 135.7 Beats per minute | Standard Deviation 9.89 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | Pre-dose | 134.8 Beats per minute | Standard Deviation 13.25 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 24 Hours | 139.6 Beats per minute | Standard Deviation 10.47 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 4 Hours | 136.3 Beats per minute | Standard Deviation 11.88 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 8 Hours | 137.4 Beats per minute | Standard Deviation 11.69 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 18 Hours | 137.8 Beats per minute | Standard Deviation 11.42 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 12 Hours | 131.4 Beats per minute | Standard Deviation 9.97 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 2 Hours | 136.6 Beats per minute | Standard Deviation 10.27 |
| Part A/B: Oral GSK221149A | Fetal Heart Rate Monitoring up to 48 Hours | 6 Hours | 139.4 Beats per minute | Standard Deviation 14 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 48 Hours | 140.5 Beats per minute | Standard Deviation 10.27 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 24 Hours | 135.2 Beats per minute | Standard Deviation 9.16 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 6 Hours | 137.1 Beats per minute | Standard Deviation 9.42 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 8 Hours | 134.1 Beats per minute | Standard Deviation 10.52 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | Pre-dose | 139.8 Beats per minute | Standard Deviation 8.49 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 2 Hours | 137.4 Beats per minute | Standard Deviation 10.8 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 12 Hours | 135.4 Beats per minute | Standard Deviation 9.14 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 18 Hours | 135.4 Beats per minute | Standard Deviation 10.68 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 36 Hours | 137.4 Beats per minute | Standard Deviation 11.98 |
| Part C: Placebo | Fetal Heart Rate Monitoring up to 48 Hours | 4 Hours | 138.3 Beats per minute | Standard Deviation 13.7 |
Primary
Number of Participants Achieving Uterine Quiescence
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.
Time frame: Up to 48 hours post-dose
Population: Pharmacodynamic Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants Achieving Uterine Quiescence | 9 Participants |
| Part C: Active (GSK221149A) | Number of Participants Achieving Uterine Quiescence | 18 Participants |
| Part A/B: Oral GSK221149A | Number of Participants Achieving Uterine Quiescence | 2 Participants |
| Part C: Placebo | Number of Participants Achieving Uterine Quiescence | 13 Participants |
Primary
Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B
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.
Time frame: Up to 48 hours post-dose
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B | 9 Participants |
| Part C: Active (GSK221149A) | Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B | 1 Participants |
Primary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
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.
Time frame: Up to Follow-up (Week 12)
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 11 Participants |
| Part A/B: IV GSK221149A | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 1 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 2 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 14 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 2 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 0 Participants |
| Part C: Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 17 Participants |
| Part C: Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 2 Participants |
Primary
Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern
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.
Time frame: Up to 24 hours post-treatment
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern | 10 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern | 22 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern | 7 Participants |
| Part C: Placebo | Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern | 28 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
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.
Time frame: Up to Follow-up (Week 12)
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | 13 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | 15 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | 8 Participants |
| Part C: Placebo | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | 9 Participants |
Primary
Number of Participants With Vital Sign Values of Potential Clinical Concern
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.
Time frame: Up to Follow-up (Week 12)
Population: Safety Population which comprised of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low systolic blood pressure | 0 Participants |
| Part A/B: IV GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low diastolic blood pressure | 1 Participants |
| Part A/B: IV GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High systolic blood pressure | 1 Participants |
| Part A/B: IV GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High diastolic blood pressure | 0 Participants |
| Part A/B: IV GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High heart rate | 2 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Vital Sign Values of Potential Clinical Concern | High diastolic blood pressure | 0 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low systolic blood pressure | 3 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Vital Sign Values of Potential Clinical Concern | High systolic blood pressure | 0 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low diastolic blood pressure | 4 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Vital Sign Values of Potential Clinical Concern | High heart rate | 4 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High diastolic blood pressure | 0 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High heart rate | 0 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low diastolic blood pressure | 0 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low systolic blood pressure | 0 Participants |
| Part A/B: Oral GSK221149A | Number of Participants With Vital Sign Values of Potential Clinical Concern | High systolic blood pressure | 0 Participants |
| Part C: Placebo | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low systolic blood pressure | 4 Participants |
| Part C: Placebo | Number of Participants With Vital Sign Values of Potential Clinical Concern | Low diastolic blood pressure | 4 Participants |
| Part C: Placebo | Number of Participants With Vital Sign Values of Potential Clinical Concern | High heart rate | 3 Participants |
| Part C: Placebo | Number of Participants With Vital Sign Values of Potential Clinical Concern | High diastolic blood pressure | 1 Participants |
| Part C: Placebo | Number of Participants With Vital Sign Values of Potential Clinical Concern | High systolic blood pressure | 1 Participants |
Secondary
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])
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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
Derived Plasma GSK221149 Pharmacokinetic Parameters- Maximum Plasma Concentration (Cmax)
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A/B: IV GSK221149A | Derived Plasma GSK221149 Pharmacokinetic Parameters- Maximum Plasma Concentration (Cmax) | 126.93 Nanogram per milliliter | Geometric Coefficient of Variation 66.4 |
Secondary
Derived Plasma GSK221149 Pharmacokinetic Parameters- Observed Elimination Half-life (T-half) and Time to Maximum Observed Drug Concentration (T-max)
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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
Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
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.
Time frame: 1 minute and 5 minute after birth at 4 to 12 weeks post adjusted gestational age
Population: Pharmacodynamic Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 |
| Part C: Active (GSK221149A) | Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | APGAR Five Minute Score | 8.9 Scores on a scale | Standard Deviation 0.34 |
| Part C: Active (GSK221149A) | Neonatal Apgar Scores (at Birth) Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | APGAR One Minute Score | 8.2 Scores on a scale | Standard Deviation 0.77 |
Secondary
Neonatal Apgar Scores in Part A and B
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.
Time frame: 1 minute and 5 minutes after birth
Population: Pharmacodynamic Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Neonatal Apgar Scores in Part A and B | APGAR Five Minute Score | 8.8 Scores on a Scale | Standard Deviation 0.72 |
| Part A/B: IV GSK221149A | Neonatal Apgar Scores in Part A and B | APGAR One Minute Score | 7.7 Scores on a Scale | Standard Deviation 1.6 |
| Part C: Active (GSK221149A) | Neonatal Apgar Scores in Part A and B | APGAR Five Minute Score | 9.0 Scores on a Scale | Standard Deviation 0 |
| Part C: Active (GSK221149A) | Neonatal Apgar Scores in Part A and B | APGAR One Minute Score | 8.2 Scores on a Scale | Standard Deviation 0.67 |
Secondary
Neonatal Head Circumference in Part A and B
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.
Time frame: At Birth and Follow-up (Week 12)
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Neonatal Head Circumference in Part A and B | At Birth | 34.145 Centimeters | Standard Deviation 1.6187 |
| Part A/B: IV GSK221149A | Neonatal Head Circumference in Part A and B | At Follow-up | 37.921 Centimeters | Standard Deviation 5.1082 |
| Part C: Active (GSK221149A) | Neonatal Head Circumference in Part A and B | At Birth | 35.903 Centimeters | Standard Deviation 7.7959 |
| Part C: Active (GSK221149A) | Neonatal Head Circumference in Part A and B | At Follow-up | 36.667 Centimeters | Standard Deviation 1.5 |
Secondary
Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
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.
Time frame: At Birth and Follow-up (Week 12)
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 |
| Part C: Active (GSK221149A) | Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth | 33.080 Centimeteres | Standard Deviation 1.6374 |
| Part C: Active (GSK221149A) | Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Follow-up | 35.160 Centimeteres | Standard Deviation 1.7792 |
Secondary
Neonatal Length Measured at 4-6 Weeks of Age in Part A and B
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Neonatal Length Measured at 4-6 Weeks of Age in Part A and B | At Birth | 50.3 Centimeters | Standard Deviation 3.18 |
| Part A/B: IV GSK221149A | Neonatal Length Measured at 4-6 Weeks of Age in Part A and B | At Follow-up | 54.6 Centimeters | Standard Deviation 3.03 |
| Part C: Active (GSK221149A) | Neonatal Length Measured at 4-6 Weeks of Age in Part A and B | At Birth | 48.7 Centimeters | Standard Deviation 3.64 |
| Part C: Active (GSK221149A) | Neonatal Length Measured at 4-6 Weeks of Age in Part A and B | At Follow-up | 53.1 Centimeters | Standard Deviation 3.04 |
Secondary
Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
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.
Time frame: At Birth and Follow-up (Week 12)
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth | 47.8 Centimeters | Standard Deviation 2.78 |
| Part A/B: IV GSK221149A | 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 |
| Part C: Active (GSK221149A) | Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth | 47.8 Centimeters | Standard Deviation 3.39 |
| Part C: Active (GSK221149A) | Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Follow-up | 51.3 Centimeters | Standard Deviation 3.3 |
Secondary
Neonatal Weight Gain in Part A and B
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.
Time frame: At birth and Follow-up (Week 12)
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | Neonatal Weight Gain in Part A and B | At Birth | 3233.81 Grams | Standard Deviation 478.8 |
| Part A/B: IV GSK221149A | Neonatal Weight Gain in Part A and B | At Follow-up | 4548.02 Grams | Standard Deviation 809.1 |
| Part C: Active (GSK221149A) | Neonatal Weight Gain in Part A and B | At Birth | 3090.33 Grams | Standard Deviation 643.2 |
| Part C: Active (GSK221149A) | Neonatal Weight Gain in Part A and B | At Follow-up | 4710.29 Grams | Standard Deviation 818 |
Secondary
Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
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.
Time frame: At birth and Follow-up (Week 12)
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 |
| Part C: Active (GSK221149A) | Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Birth | 2940.03 Grams | Standard Deviation 584.95 |
| Part C: Active (GSK221149A) | Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C | At Follow-up | 3601.79 Grams | Standard Deviation 659.479 |
Secondary
Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C
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.
Time frame: 48 hours post-dose
Population: Pharmacodynamic Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C | 30 Participants |
| Part C: Active (GSK221149A) | Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C | 34 Participants |
Secondary
Number of Participants With Preterm Births in Part C
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.
Time frame: Up to 48 hours post-dose
Population: Pharmacodynamic Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A/B: IV GSK221149A | Number of Participants With Preterm Births in Part C | 5 Participants |
| Part C: Active (GSK221149A) | Number of Participants With Preterm Births in Part C | 16 Participants |
Secondary
Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C
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.
Time frame: First 6 hours of therapy
Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 42.2 |
| Part A/B: IV GSK221149A | 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 |
| Part A/B: IV GSK221149A | 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 43.29 |
| Part A/B: IV GSK221149A | 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 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 5 Hour | -51.78 Percent change | Standard Deviation 49.544 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 1 Hour | -19.03 Percent change | Standard Deviation 41.345 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 4 Hour | -35.56 Percent change | Standard Deviation 69.171 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 2 Hour | -27.67 Percent change | Standard Deviation 58.181 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 6 Hour | -49.26 Percent change | Standard Deviation 47.871 |
| Part C: Active (GSK221149A) | Percentage Reduction From Baseline in Number of Uterine Contractions [>30 Sec] Per Hour Within First 6 Hours of Therapy in Part C | 3 Hour | -23.11 Percent change | Standard Deviation 68.82 |