E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023555 |
E.1.2 | Term | Labour premature |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To describe the maternal safety and tolerability of GSK221149A administered intravenously to healthy pregnant women in PTL between 30 0/7 and 35 6/7 weeks gestation 2. To describe the fetal safety and tolerability of GSK221149A administered intravenously to healthy pregnant women in PTL between 30 0/7 and 35 6/7 weeks gestation 3. To evaluate the pharmacodynamics of GSK221149A in pregnant women in preterm labor between 30 0/7 and 35 6/7 weeks gestation 4. To characterize the pharmacokinetics of GSK221149A administered intravenously to pregnant females in preterm labor between 300/7 and 356/7 weeks gestation
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E.2.2 | Secondary objectives of the trial |
To describe the effect of maternal treatment with GSK221149A on short term neonatal growth and well-being |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. At least 18 to 45 years of age inclusive 2. 30 0/7 -35 6/7 weeks (best obstetric estimate, preferably first trimester ultrasound) with singleton pregnancy 3. Symptoms of preterm labor: contractions at a frequency of ≥ 4 per 30 min or ≥ 6 per hour, each of at least 30 sec in duration and confirmed by tocodynamometry 4. Cervical dilatation ≥1 to ≤4 cm. Subjects can not exceed a maximum cervical dilation of 4 cm to be included in this study at the time of screening 5. Intact fetal membranes 6. Ability to understand and provide written informed consent to participate in this study 7. Women with gestational diabetes diagnosed during current pregnancy and controlled by diet and exercise will be permitted into this study. Women must have a nonfasting glucose level at screening between 70 mg/dL ≤ 130 mg/dL by point-of-care glucometer or between 70 mg/dL ≤ 140 mg/dL by local laboratory determination to be enrolled in the study 8. Women previously administered tocolytic treatment, which has been discontinued by the investigator for lack of efficacy or intolerance, do not require a 24-hour washout period if otherwise eligible for the study |
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E.4 | Principal exclusion criteria |
1. 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 2. Patients who have received a cervical cerclage currently or in a previous pregnancy 3. Any clinically relevant preexisting or pregnancy-related co-morbid condition that may affect maternal pregnancy outcome or neonatal outcome (eg. hypertension, diabetes mellitus, bleeding/clotting diathesis) 4. Patients who have received a third trimester amniocentesis. Patients who have received a first and second trimester amniocentesis are allowed in the study if the results are normal 5. Women with gestational diabetes requiring insulin or pre-existing diabetes mellitus are excluded from this study. Use of oral antidiabetic agents for gestational diabetes is also exclusionary 6. Known fetal intrauterine growth restriction or fetal congenital anomaly 7. Abnormal modified biophysical profile (NST is non-reactive and AFI <5) 8. Participation in another interventional (i.e any study involving an investigational product or device) clinical trial during the current pregnancy. Women enrolled in a observational, non-interventional, non-device trial will be permitted into the study. 9. Abuse of alcohol, defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units. One unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits, or 1 glass (125mL of wine) 10. History of anaphylaxis or anaphylactoid reactions, or severe allergic responses to drugs 11. Known to be positive for hepatitis C antibody, hepatitis B surface antigen or HIV on prenatal laboratory results 12. Use of prescription drugs that are potent CYP3A4 inhibitors, within 7 days or 5 half-lives (whichever is longer) prior to first dose of medication 13. Use of dietary/herbal supplements including (but not limited to) St. John's wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, ginseng, and red yeast rice (2-fold greater than the recommended daily allowance of 1200 mg per day) within 7 days prior to first dose of medication 14. Consumption of grapefruit or grapefruit juice within 3 days prior to first dose of medication 15. QTc > 450 msec (either QTcb or QTcf, machine or manual overread, on single or average QTc value of triplicate ECGs obtained over a brief recording period.) 16. QTc > 480 msec for patients with Bundle Branch Block 17. Use of illicit drugs or positive urine drug screen any time during pregnancy 18. Any contraindication to tocolytic therapy, including (but not limited to) suspected intrauterine infection, vaginal bleeding (including ante-partum hemorraghe), pre-eclampsia/eclampsia, placenta previa, removal of placenta, and intrauterine fetal death. 19. Trauma within 48 hours of presentation in preterm labor 20. Subjects previously enrolled in Study OTA105256 21. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Maternal safety and tolerability, (vital signs, ECGs, clinical laboratory tests, adverse events) during acute therapy and for approximately 48 hours after the initiation of therapy compared to placebo and baseline 2. Assessment of fetal heart rate and amniotic fluid index (AFI) measurements before, during, and after treatment with GSK221149A compared to placebo and baseline 3. Proportion of patients who achieve >= 50% reduction in number of contractions [contractions defined in part by lasting at least 30 seconds, abbreviated as: >30 secs] per hour from baseline together with no cervical dilation increase within the first 6 hours of therapy
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be the last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |