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

NCT00404768 | Completed Phase 2 Results

• 1 other identifier: OTA105256
• Study Type: interventional
• Target: 93
• Locations: 11 countries
• Sites: 57

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.

Conditions

Obstetric Labour, Premature

Keywords

Premature Labor; Pre Term Labor; intravenous; fetal fibronectin

Outcome Measures

Primary Outcomes (8)

• 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.

  Up to Follow-up (Week 12)

• 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.

  Up to Follow-up (Week 12)

• 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.

  Up to 24 hours post-treatment

• 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.

  Up to Follow-up (Week 12)

• 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.

  Up to 48 hours-post dose

• 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.

  Up to 48 hours post-dose

• 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.

  Up to 48 hours post-dose

• 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.

  Up to 48 hours post-dose

Secondary Outcomes (14)

• Number of Participants With Preterm Births in Part C

  Up to 48 hours post-dose

• Neonatal Apgar Scores in Part A and B

  1 minute and 5 minutes after birth

• Neonatal Weight Gain in Part A and B

  At birth and Follow-up (Week 12)

• Neonatal Head Circumference in Part A and B

  At Birth and Follow-up (Week 12)

• 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)

Study Arms (2)

Treatment

EXPERIMENTAL

GSK221149A

Drug: GSK221149A

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GSK221149A DRUG

6mg/h and 12 mg/h

Treatment

Placebo DRUG

Matched Placebo to Drug

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy pregnant females, 30 -36 weeks pregnant, without ruptured membranes
• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (57)

GSK Investigational Site

Mobile, Alabama, 36604, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85008, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85013, United States

Location

GSK Investigational Site

Tucson, Arizona, 85712, United States

Location

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Colton, California, 92324, United States

Location

GSK Investigational Site

Loma Linda, California, 92350, United States

Location

GSK Investigational Site

Los Angeles, California, 90033, United States

Location

GSK Investigational Site

Newark, Delaware, 19718, United States

Location

GSK Investigational Site

Idaho Falls, Idaho, 83404, United States

Location

GSK Investigational Site

Kansas City, Kansas, 66160, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55454, United States

Location

GSK Investigational Site

St Louis, Missouri, 63023, United States

Location

GSK Investigational Site

Newark, New Jersey, 07101-1709, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Southern Pines, North Carolina, 28388, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45267, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19102, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Columbia, South Carolina, 29201, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37403, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37920-1511, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38119, United States

Location

GSK Investigational Site

Galveston, Texas, 77555-0587, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Houston, Texas, 77054, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84124, United States

Location

GSK Investigational Site

West Jordan, Utah, 84088, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23507-1914, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1181, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1259, Argentina

Location

GSK Investigational Site

Sofia, 1431, Bulgaria

Location

GSK Investigational Site

Sofia, Bulgaria

Location

GSK Investigational Site

Bogotá, Colombia

Location

GSK Investigational Site

Clamart, 92141, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Paris, 75679, France

Location

GSK Investigational Site

Poissy, 78300, France

Location

GSK Investigational Site

Suresnes, 92150, France

Location

GSK Investigational Site

Kaunas, LT-50009, Lithuania

Location

GSK Investigational Site

Vilnius, LT-10207, Lithuania

Location

GSK Investigational Site

San Juan, 00935, Puerto Rico

Location

GSK Investigational Site

Singapore, 229899, Singapore

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

GSK Investigational Site

Barakaldo (Vizcaya), 48903, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Valencia, 46009, Spain

Location

GSK Investigational Site

Warwick, Warwickshire, CV34 5BW, United Kingdom

Location

GSK Investigational Site

Coventry, CV2 2DX, United Kingdom

Location

GSK Investigational Site

London, SE1 7EH, United Kingdom

Location

GSK Investigational Site

London, W12 0NN, United Kingdom

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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.

  PMID: 28556962 BACKGROUND

• 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. Erratum In: Br J Clin Pharmacol. 2015 Sep;80(3):609. doi: 10.1111/bcp.12694.

  PMID: 25819462 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Premature Birth; Obstetric Labor, Premature

Interventions

GSK221149A

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2006
• First Posted: November 29, 2006
• Study Start: October 12, 2007
• Primary Completion: July 7, 2011
• Study Completion: July 7, 2011
• Last Updated: January 16, 2018
• Results First Posted: December 13, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will share

Locations

AR (2); US (32); SG (1); CO (1); GB (4); KR (3); PR (1); LI (2); BU (2); FR (5); ES (4)