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

Study at a glance

From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT00404768

Acronym / sponsor ID

OTA105256

Conditions

Obstetric Labour, Premature

Keywords

Premature Labor, Pre Term Labor, intravenous, fetal fibronectin

Phase

Phase 2

Study type

Interventional

Recruitment status

Completed

Enrolment

93 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

12 Oct 2007 (actual)

Primary completion

7 Jul 2011 (actual)

Study completion

7 Jul 2011 (actual)

First posted

29 Nov 2006 (estimated)

Results

Posted 13 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Triple blind (participant, care provider, investigator)

Number of arms

2

Who may qualify

Ages

18 to 45 years

Sex

Female only

Healthy volunteers

Not accepted

Age groups

Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Vital Sign Values of Potential Clinical Concern

   Time frame: 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.

2. Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern

   Time frame: 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.

3. Number of Participants With Clinical Chemistry and Hematology Parameter Values of Potential Clinical Concern

   Time frame: 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.

4. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

   Time frame: 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.

5. Assessment of Amniotic Fluid Index (AFI)

   Time frame: 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.

6. Number of Participants With 50% Reduction in Uterine Contractions Per Hour in Part A and B

   Time frame: 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.

7. Fetal Heart Rate Monitoring up to 48 Hours

   Time frame: 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.

8. Number of Participants Achieving Uterine Quiescence

   Time frame: 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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2018.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• BackgroundJerry 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: PubMed 28556962Thornton 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.
• Background: PubMed 25819462Thornton 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.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
• Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

57 sites in 11 countries: see every site and its status.