Clinical trial NCT00404768: The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstetric Labour, Premature
Keywords: Premature Labor
Pre Term Labor
intravenous
fetal fibronectin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-11-29
Enrollment: 93
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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)

Primary outcomes:
measure: Number of Participants With Vital Sign Values of Potential Clinical Concern
timeFrame: Up to Follow-up (Week 12)
measure: Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
timeFrame: Up to Follow-up (Week 12)
measure: Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern
timeFrame: Up to 24 hours post-treatment
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Follow-up (Week 12)
measure: Assessment of Amniotic Fluid Index (AFI)
timeFrame: Up to 48 hours-post dose
measure: Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B
timeFrame: Up to 48 hours post-dose
measure: Fetal Heart Rate Monitoring up to 48 Hours
timeFrame: Up to 48 hours post-dose
measure: Number of Participants Achieving Uterine Quiescence
timeFrame: Up to 48 hours post-dose
Secondary outcomes:
measure: Number of Participants With Preterm Births in Part C
timeFrame: Up to 48 hours post-dose
measure: Neonatal Apgar Scores in Part A and B
timeFrame: 1 minute and 5 minutes after birth
measure: Neonatal Weight Gain in Part A and B
timeFrame: At birth and Follow-up (Week 12)
measure: Neonatal Head Circumference in Part A and B
timeFrame: At Birth and Follow-up (Week 12)
measure: 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)
measure: 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
measure: 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
measure: 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
measure: 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
measure: Neonatal Weight Gain Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
timeFrame: At birth and Follow-up (Week 12)
measure: Neonatal Head Circumference Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
timeFrame: At Birth and Follow-up (Week 12)
measure: Neonatal Length Measured at 4 to 12 Weeks Post Adjusted Gestational Age in Part C
timeFrame: At Birth and Follow-up (Week 12)
measure: Number of Participants Who Remained Undelivered Without Rescue Tocolytic Therapy After 48 Hours in Part C
timeFrame: 48 hours post-dose
measure: 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
Other outcomes:
Locations:
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Jonesboro
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Colton
country: United States
facility: GSK Investigational Site
state: California
city: Loma Linda
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newark
country: United States
facility: GSK Investigational Site
state: Delaware
city: Idaho Falls
country: United States
facility: GSK Investigational Site
state: Idaho
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Southern Pines
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Galveston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: West Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Bogotá
country: Colombia
facility: GSK Investigational Site
city: Clamart cedex
country: France
facility: GSK Investigational Site
city: Lille cedex
country: France
facility: GSK Investigational Site
city: Paris cedex 14
country: France
facility: GSK Investigational Site
city: Poissy
country: France
facility: GSK Investigational Site
city: Suresnes
country: France
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Kaunas
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Barakaldo (Vizcaya)
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Warwick
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Thornton S, Valenzuela G, Baidoo C, Fossler MJ, Montague TH, Clayton L, Powell M, Snidow J, Stier B, Soergel D. Treatment of spontaneous preterm labour with retosiban: a phase II pilot dose-ranging study. Br J Clin Pharmacol. 2017 Oct;83(10):2283-2291. doi: 10.1111/bcp.13336. Epub 2017 Jul 11.
citation: Thornton S, Miller H, Valenzuela G, Snidow J, Stier B, Fossler MJ, Montague TH, Powell M, Beach KJ. Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study. Br J Clin Pharmacol. 2015 Oct;80(4):740-9. doi: 10.1111/bcp.12646. Epub 2015 Jun 1.