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 | 10036594 |
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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 |
The primary objective of this study is to determine if treatment with 17P reduces the rate of preterm birth < 350 weeks of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to: Determine if 17P reduces the rate of neonatal mortality or morbidity, if and only if, the rate of preterm birth < 350 weeks of gestation is statistically significant (i.e., hierarchical testing approach). Neonatal mortality or morbidity is measured by a composite index comprised of o Neonatal death. o Grade 3 or 4 intraventricular hemorrhage. o Respiratory distress syndrome. o Bronchopulmonary dysplasia. o Necrotizing enterocolitis. o Proven sepsis. Exclude a doubling of the risk of fetal/early infant death, defined as spontaneous abortion/miscarriage (delivery from 160 through 196 weeks of gestation) or death (from minutes after birth until 28 days of life) occurring in liveborns born at less than 24 weeks gestation or stillbirth (antepartum or intrapartum death from 20 weeks gestation through term), in the 17P group compared to the vehicle group. Determine if 17P reduces the rate of preterm birth < 320 weeks of gestatio |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years. 2. Singleton gestation. 3. Project gestational age 160 weeks of gestation or more and less than or equal to 206 weeks of gestation at the time of randomization, based on clinical information and evaluation of the first ultrasound. 4. Documented history of a previous singleton spontaneous preterm delivery. Spontaneous preterm birth is defined as delivery from 200 to 366 weeks of gestation following spontaneous preterm labor or pPROM. Where possible, the gestational age of the previous preterm birth (referred to as the qualifying delivery) should be determined as described in Gestational Age Determination below. If the gestational age at delivery is obtained directly from the medical record and more than one gestational age appears, the latest will be used. As a validation of the gestational age of the previous delivery, if the infant weighed more than 3300 grams (the birth weight 90th percentile for 36 weeks gestational age), this will not qualify as preterm. The previous preterm delivery cannot be an antepartum stillbirth. |
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E.4 | Principal exclusion criteria |
1. Multifetal gestation. 2. Known major fetal anomaly or fetal demise. An ultrasound examination between 140 through 203 weeks of gestation must be performed to rule out fetal anomalies. 3. Progesterone treatment in any form (i.e., vaginal, oral, intramuscular) during current pregnancy. 4. Heparin therapy during current pregnancy or history of thromboembolic disease. 5. Maternal medical/obstetrical complications including: Current or planned cerclage Hypertension requiring medication Seizure disorder 6. Subjects with a uterine anomaly (uterine didelphus or bicornate uterus). However, subjects with uterine fibroids are eligible for the study. 7. Unwillingness to comply with and complete the study. 8. A 140 through 203 weeks of gestation ultrasound cannot be arranged before randomization. 9. Participation in an antenatal study in which the clinical status or intervention may influence gestational age at delivery. 10. Participation in this trial in a previous pregnancy. Women who were screened in a previous pregnancy, but not randomized, do not have to be excluded. 11. Known hypersensitivity to hydroxyprogesterone caproate or its components. 12. Have any significant medical disorder that, in the opinion of the investigator, would be a contraindication to the use of the drug including those listed in section 5.3.2 of the investigational brochure. Other examples to consider include uncontrolled diabetes, known HIV infection or renal dysfunction. 13. Have any significant medical disorder that, in the opinion of the investigator, would preclude accurate evaluation of the subjects condition or outcome in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome is preterm birth prior to 350 weeks of gestaion as determined by project gestational age, which will be evaluated in a standardized manner. |
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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 | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Ultima visita dell`ultimo paziente |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |