Last updated: 11/04/2018 10:07:49
The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with vital sign values of potential clinical concern
Timeframe: Up to Follow-up (Week 12)
Number of participants with electrocardiogram (ECG) values of potential clinical concern
Timeframe: Up to Follow-up (Week 12)
Number of participants with clinical chemistry and hematology parameter values of potential clinical concern
Timeframe: Up to 24 hours post-treatment
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to Follow-up (Week 12)
Assessment of amniotic fluid index (AFI)
Timeframe: Up to 48 hours-post dose
Number of participants with 50% reduction in uterine contractions per hour in Part A and B
Timeframe: Up to 48 hours post-dose
Fetal heart rate monitoring up to 48 hours
Timeframe: Up to 48 hours post-dose
Number of participants Achieving Uterine Quiescence
Timeframe: Up to 48 hours post-dose
Secondary outcomes:
Number of participants with preterm births in Part C
Timeframe: Up to 48 hours post-dose
Neonatal Apgar scores in Part A and B
Timeframe: 1 minute and 5 minutes after birth
Neonatal weight gain in Part A and B
Timeframe: At birth and Follow-up (Week 12)
Neonatal head circumference in Part A and B
Timeframe: At Birth and Follow-up (Week 12)
Neonatal length measured at 4-6 weeks of age in Part A and B
Timeframe: At birth and follow-up (approximately 4 to 6 weeks of age)
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])
Timeframe: 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)
Timeframe: 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)
Timeframe: Pre-dose, 2, 4, 8, 12, 24 and 48 (just before infusion was stopped) hours after the start of the infusion
Neonatal Apgar scores (at birth) measured at 4 to 12 weeks post adjusted gestational age in Part C
Timeframe: 1 minute and 5 minute after birth at 4 to 12 weeks post adjusted gestational age
Neonatal weight gain measured at 4 to 12 weeks post adjusted gestational age in Part C
Timeframe: At birth and Follow-up (Week 12)
Neonatal head circumference measured at 4 to 12 weeks post adjusted gestational age in Part C
Timeframe: At Birth and Follow-up (Week 12)
Neonatal length measured at 4 to 12 weeks post adjusted gestational age in Part C
Timeframe: At Birth and Follow-up (Week 12)
Number of participants who remained undelivered without rescue tocolytic therapy after 48 hours in Part C
Timeframe: 48 hours post-dose
Percentage reduction from Baseline in number of uterine contractions [>30 sec] per hour within first 6 hours of therapy in Part C
Timeframe: First 6 hours of therapy
Interventions:
Drug: GSK221149A
Drug: Placebo
Enrollment:
93
Observational study model:
Not applicable
Primary completion date:
2011-22-06
Time perspective:
Not applicable
Clinical publications:
Jerry Snidow, Hugh Miller, Guillermo Valenzuela, Steve Thornton, Brendt Stier, Linda Clayton, Michael Fossler, Timothy Montague, Kathleen Beach, Pauline Williams. A Multicenter, Randomized, Double-blind Placebo-controlled Phase II Trial of Retosiban, a Selective Oxytocin Receptor Antagonist, for the Management of Preterm Labor. Am J Obstet Gynecol. 2013;2:S155.
Thornton S. et al. Treatment of spontaneous preterm labour with retosiban: a phase 2 pilot dose-ranging study. Br. J. Clin. Pharmacol. 2017; Oct, 83(10): 2283-2291
Thornton S. et al. Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study. Br. J. Clin. Pharmacol. 2015; Oct, 80(4): 740-749
S Thornton, H Miller, G Valenzuela, J Snidow, B Stier, MFossler, T Montague, M Powell, K Beach.Treatment of Spontaneous Preterm Labour with Retosiban: A Phase 2 Proof-of-Concept Study .Br J Clin Pharmacol.2015;80(4):740-749
Medical condition
Obstetric Labour, Premature
Product
retosiban
Collaborators
Not applicable
Study date(s)
October 2007 to June 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female
Age
18 - 45 years
Accepts healthy volunteers
No
- Healthy pregnant females, 30 -36 weeks pregnant, without ruptured membranes
- 18-45 inclusive
- 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)
Inclusion and exclusion criteria
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)
Trial location(s)
Location
GSK Investigational Site
Colton, California, United States, 92324
Status
Study Complete
Location
GSK Investigational Site
Idaho Falls, Idaho, United States, 83404
Status
Study Complete
Location
GSK Investigational Site
Mobile, Alabama, United States, 36604
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29425
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Los Angeles, California, United States, 90033
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85013
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1259
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45267
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85008
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Knoxville, Tennessee, United States, 37920-1511
Status
Study Complete
Location
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27514
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Houston, Texas, United States, 77030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newark, Delaware, United States, 19718
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Salt lake City, Utah, United States, 84124
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38119
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55454
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chattanooga, Tennessee, United States, 37403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Loma Linda, California, United States, 92350
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63023
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19102
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23507-1914
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kansas City, Kansas, United States, 66160
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Barakaldo (Vizcaya), Spain, 48903
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newark, New Jersey, United States, 07101-1709
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Southern Pines, North Carolina, United States, 28388
Status
Study Complete
Location
GSK Investigational Site
Jonesboro, Arkansas, United States, 72401
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1181
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Warwick, Warwickshire, United Kingdom, CV34 5BW
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Galveston, Texas, United States, 77555-0587
Status
Study Complete
Location
GSK Investigational Site
West Jordan, Utah, United States, 84088
Status
Study Complete
Location
GSK Investigational Site
Columbia, South Carolina, United States, 29201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Juan, Puerto Rico, Puerto Rico, 00935
Status
Will Be Recruiting
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-22-06
Actual study completion date
2011-22-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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