Clinical Trials Register

Summary
EudraCT Number:	2014-001826-13
Sponsor's Protocol Code Number:	200721
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-05-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-001826-13

A.3

Full title of the trial

Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban Therapy for Women in Spontaneous Preterm Labor

Studio di fase III, multicentrico, randomizzato, in doppio cieco, per confrontare l’efficacia e la sicurezza della terapia con Retosiban versus Atosiban nelle donne con travaglio pretermine spontaneo

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The purpose of this study is to compare Retosiban with Atosiban and show that retosiban is more effective in stopping spontaneous preterm labor and prolonges labor

Lo scopo di questo studio è confrontare Retosiban con Atosiban e dimostrare che Retosiban è più efficace dell'interruzione dl travaglio pretermine spontaneo e nel prolungamento del travaglio

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

200721

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

A.5.4

Other Identifiers

Name:

Number:

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/20/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	Robert Stocken
B.5.3	Address:
B.5.3.1	Street Address	Stockley Park West, 1-3 Ironbridge Road
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 1BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02089903879
B.5.5	Fax number	02089903511
B.5.6	E-mail	robert.c.stocken@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Retosiban
D.3.2	Product code	GSK221149
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Retosiban
D.3.9.1	CAS number	820957-38-8
D.3.9.2	Current sponsor code	GSK221149
D.3.9.4	EV Substance Code	SUB29510
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tractocile
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Pharmaceuticals A/S
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tractocile
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Pharmaceuticals A/S
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

preterm labor

Travaglio pretermine

E.1.1.1

Medical condition in easily understood language

Restosiban stops preterm labor and prolongs pregnancy

Retosiban blocca il travaglio pretermine e prolunga la gravidanza

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10073024
E.1.2	Term	Preterm premature rupture of membranes
E.1.2	System Organ Class	10036585 - Pregnancy, puerperium and perinatal conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the superiority of retosiban to prolong pregnancy compared with atosiban

L'obiettivo primario è dimostrare la superiorità di retosiban nel prolungare la gravidanza rispetto ad atosiban.

E.2.2

Secondary objectives of the trial

To describe the outcomes of newborns during the neonatal period (through 28 days post estimated date of delivery [EDD]) for retosiban compared with atosiban
To describe the maternal, fetal, and neonatal safety profile during and after IV retosiban treatment compared with atosiban treatment
To determine the effect of retosiban treatment compared with atosiban on health care resource use and patient-reported outcomes associated with the maternal and neonatal hospitalization
To obtain further data on the pharmacokinetics of retosiban in pregnant women, including the effect of covariates such as age, weight, race/ethnicity, and GA on retosiban clearance and volume of distribution

Descrivere il profilo di sicurezza materno, fetale e neonatale durante e dopo il trattamento con retosiban per via endovenosa (IV) rispetto al trattamento con atosiban;
-Determinare l'effetto del trattamento con retosiban rispetto ad atosiban per quanto riguarda l'uso di risorse per l'assistenza sanitaria e gli esiti riportati dal paziente in associazione con la degenza ospedaliera materna e neonatale;
-Ottenere ulteriori informazioni sulla farmacocinetica di retosiban nelle donne in gravidanza, incluso l'effetto delle covariate come l'età, il peso, la razza/etnia e la GA sulla clearance di retosiban e sul volume di distribuzione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Signed and dated written informed consent is required prior to a subject’s participation in the study and the performance of any protocol specific procedures. Adolescents aged 12 to 17 years must provide written agreement to participate in the study in accordance with applicable regulatory and country or state requirements. Subjects will also be asked to sign a release for medical records at the time of consenting to allow access to both the maternal and neonatal records including information about delivery and infant care as well as information collected prior to the consent having been signed
Note: Prescreening alone does not necessarily require consent as this activity may be accomplished in the absence of study specific procedures or assessments. In many cases, standard care and standard medical triage will provide sufficient information or evidence as to whether or not the subject is eligible for the study
2.Females aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in preterm labor (Note: This protocol includes pregnant adolescents, aged 12 to 17 years, as appropriate, based on national or local regulations.)
3.Gestational age between 240/7 and 336/7 weeks as determined by (1) known fertilization date, either in vitro fertilization or intrauterine insemination, (2) last menstrual period confirmed by the earliest ultrasound prior to 240/7 weeks’ gestation, or (3) the earliest ultrasound alone prior to 240/7 weeks’ gestation, whichever is the most accurate method available for each subject. In situations where prenatal ultrasound records are not available at the time the subject presents, the investigator will make every effort to obtain these records (either via computer records, directly from the subject’s primary care obstetrician, or via telephone). However, in cases in which these records are not readily available (e.g., off hours, holiday), it is within the investigator’s discretion to use GA based on a verbal history from the subject with the intent of getting confirmation from the medical records as soon as possible
4.Subjects must be diagnosed with preterm labor according to both of the following criteria:
a.Regular uterine contractions at a rate of ≥4 contractions of at least 30 seconds duration during a 30-minute interval confirmed by tocodynamometry
AND at least 1 of the following:
b.Cervical dilation ≥2 cm and ≤4 cm by digital cervical examination OR
c.If <2 cm dilation by digital cervical examination, a cervical change consisting of an increase of at least 25% effacement or 1 cm dilation
5.Treatment naïve subjects and subjects not adequately responding to tocolytics other than atosiban (e.g., transfers from other care units) during their current episode of preterm labor may be eligible for the study. Historical failure of a tocolytic treatment in a previous episode of preterm labor is not a required inclusion criterion. Tocolytic failure is defined by progressive cervical changes or continuing uterine contractions

I soggetti idonei per l'arruolamento allo studio devono soddisfare tutti i seguenti criteri:
1. Il consenso informato scritto, datato e firmato è necessario prima della partecipazione allo studio da parte del soggetto e prima che venga eseguita qualsiasi procedura specifica indicata nel protocollo.. Alle pazienti verrà inoltre chiesto di firmare un modulo per il rilascio di documentazione medica nel momento in cui firmano il consenso, al fine di autorizzare l'accesso alle cartelle cliniche materne e del neonato, incluse le informazioni relative al parto e alla cura del bambino nonché alle informazioni raccolte prima della firma del consenso
Nota: il pre-screening da solo non richiede necessariamente il consenso, poiché questa attività può essere completata in assenza di procedure o valutazioni specifiche dello studio. In molti casi, le cure standard e il triage medico standard forniscono le informazioni o le prove necessarie per determinare se il soggetto è idoneo per lo studio oppure no
2. Donne di età compresa tra i 18 e i 45 anni, con gravidanza singola non complicata e membrane intatte in travaglio pretermine
3. Età gestazionale dalla 240/7 alla 336/7 settimana determinata da (1) data di fecondazione nota, fecondazione in vitro o inseminazione intrauterina, (2) ultimo ciclo mestruale confermato dalla prima ecografia eseguita prima della settimana 240/7 di gestazione, o (3) la sola prima ecografia eseguita prima della settimana 240/7 di gestazione, a seconda di quale sia il metodo di valutazione più accurato disponibile per ciascun soggetto. Nelle situazioni in cui le cartelle dell'ecografia prenatale non sono disponibili nel momento in cui la paziente si presenta, lo sperimentatore profonderà tutti gli sforzi possibili per ottenere queste cartelle (attraverso i dati in formato elettronico ottenuti direttamente dall'ostetrico della paziente o per via telefonica). Tuttavia, nei casi in cui le cartelle non sono subito disponibili (es. ore di pausa, vacanze), è a discrezione dello sperimentatore l'uso della GA basata sulla storia verbale della paziente con l'intento di ricevere conferma dalle cartelle cliniche il prima possibile
4. Alle pazienti deve essere diagnosticato un travaglio pretermine secondo entrambi i criteri seguenti:
a. Contrazioni uterine regolari con una frequenza di ≥4 contrazioni della durata di almeno 30 secondi durante un intervallo di 30 minuti confermato da tocodinamometro.
E almeno uno dei seguenti:
b. Dilatazione cervicale ≥2 cm e ≤4 cm secondo l'esame digitale della cervice OPPURE
c. Se la dilatazione è <2 cm secondo l'esame digitale della cervice, un cambiamento della cervice consistente in un aumento della maturazione almeno del 25% o 1 cm di dilatazione
5. Le pazienti naive al trattamento e le pazienti che non rispondono adeguatamente ai tocolitici diversi da atosiban (es., trasferimenti da altri reparti) durante il loro attuale episodio di travaglio pretermine possono essere idonee per lo studio. Una storia di fallimento del trattamento tocolitico in un precedente episodio di travaglio pretermine non è un criterio di inclusione richiesto. Il fallimento del trattamento tocolotico è definito da cambiamenti progressivi della cervice o contrazioni uterine continue.

E.4

Principal exclusion criteria

1.Fever with a temperature greater than 100.4°F (38°C) for more than 1 hour or ≥101°F (38.3°C) in the 24 hours prior to the start of study treatment
2.Women with maternal-fetal conditions that potentially necessitate the need for delivery, such as pre-eclampsia or fetal compromise
3.A fetus with any diagnosis, condition, treatment, or other factor that in the opinion of the investigator has the potential to affect or confound assessments of efficacy or safety (e.g., nonreassuring fetal status, intrauterine growth restriction, major congenital anomaly)
4.Preterm premature rupture of membranes
5.Women with any confirmed or suspected contraindication to prolongation of pregnancy, such as placental abruption, chorioamnionitis, or placenta previa
6.Evidence of polyhydramnios (amniotic fluid index [AFI] >25 cm) or oligohydramnios (AFI <5 cm)
7.Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes, such as uncontrolled hypertension, uncontrolled diabetes (if known, history of glycosylated hemoglobin >8% at any time during pregnancy), or compromise the safety of the subject, such as underlying cardiovascular disorder (specifically ischemic cardiac disease, congenital heart disease, pulmonary hypertension, valvular heart disease, arrhythmias, and cardiomyopathy)
8.Women with a history of substance abuse or urine drug screen findings suggestive of substance abuse that may either be implicated as the cause of preterm labor (e.g., abuse of cocaine or methamphetamines) or have the potential to complicate the pregnancy outcome (e.g., alcohol abuse or opioid addiction)
9.Women with any diagnosis, condition, treatment, or other factor that in the opinion of the investigator has the potential to affect or confound assessments of efficacy or safety
10.Women with documented active hepatitis B or hepatitis C viral infection, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
11.History of sensitivity to the IPs or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK/PPD medical monitor,

1. Febbre con una temperatura superiore a 38 °C per più di un'ora o 38,3 °C nelle 24 ore precedenti l'inizio del trattamento dello studio
2. Donne con condizioni materne-fetali che implichino potenzialmente la necessità di partorire, come preeclampsia o compromissione fetale
3. Un feto con qualunque diagnosi, condizione, trattamento o altro fattore che secondo l'opinione dello sperimentatore può potenzialmente compromettere o confondere l'efficacia o la sicurezza (es. stato fetale non rassicurante, restrizione della crescita intrauterina, anomalie congenite rilevanti)
4. Rottura prematura pretermine delle membrane
5. Donne con sospetta o confermata controindicazione al prolungamento della gravidanza, come nel caso di distacco placentare, corioamniosite o placenta previa
6. Evidenza di polidramniosi (indice liquido amniotico [AFI] >25 cm) o oligoidramniosi (AFI <5 cm)
7. Donne con condizione mediche o ostetriche di co-morbilità che secondo l'opinione dello sperimentatore possono potenzialmente complicare il corso e l'esito della gravidanza, come ipertensione non controllata, diabete non controllato (se nota, anamnesi di emoglobina glicosilata >8% in qualsiasi momento durante la gravidanza), o compromettere la sicurezza della paziente, come nel caso di malattia cardiovascolare preesistente (nello specifico, malattia cardiaca ischemica, malattia cardiaca congenita, ipertensione polmonare, malattia valvolare cardiaca, aritmie, e cardiomiopatia)
8. Donne con anamnesi di abuso di sostanze o esame tossicologico delle urine con risultati che suggeriscono un abuso di sostanze che può essere implicato come la causa del travaglio pretermine (es. abuso di cocaina o anfetamine) o può potenzialmente complicare l'esito della gravidanza (es. abuso di alcol o dipendenza da oppioidi)
9. Donne con qualunque diagnosi, condizione, trattamento o altro fattore che secondo l'opinione dello sperimentatore può potenzialmente compromettere o confondere le valutazioni di efficacia o di sicurezza
10. Donne con epatite B documentata o infezione virale da epatite C, malattia epatica instabile (come definita dalla presenza di ascite, encefalopatia, coagulopatia, ipoalbuminemia, varici esofagee o gastriche o ittero persistente), cirrosi, anomalie biliari (fatta eccezione per sindrome di Gilbert o calcoli biliari asintomatici)
11. Anamnesi di sensibilità all'IP o ai suoi componenti o anamnesi di allergia a farmaci o di altra allergia che, a giudizio dello sperimentatore o del medical monitor GSK/PPD, costituisca una controindicazione alla partecipazione.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is time to delivery from the start of IP administration until delivery,

L'endpoint primario di efficacia è il tempo al parto dall'inizio della somministrazione dell'IP fino al parto, sulla base di una revisione delle cartelle.

E.5.1.1

Timepoint(s) of evaluation of this end point

48 hours after IP infusion, then every week till delivery.

48 ore dopo l'infusione dell'IMP, successivamente ogni settimana dopo il parto.

E.5.2

Secondary end point(s)

The following are the key secondary efficacy endpoints:
Proportion of births prior to 370/7 weeks’ gestation
Proportion of births at term (370/7 to 416/7 weeks’ gestation)
Length of neonatal hospital stay
Proportion of neonates with any diagnosis from the neonatal morbidity and mortality composite determined up to 28 days after EDD (of 400/7 weeks) (details for each composite are provided in Section 6.2.2)
Fetal or neonatal death
Respiratory distress syndrome (RDS)
Bronchopulmonary dysplasia
Necrotizing enterocolitis or isolated perforation
Sepsis
Meningitis
Retinopathy of prematurity
Intraventricular hemorrhage (IVH)
White matter injury,
Cerebellar hemorrhage

The following are other secondary efficacy endpoints:
Proportion of neonates with any of the composite neonatal morbidity and mortality excluding RDS
Proportion of neonates with each individual component of the composite neonatal morbidity and mortality endpoints
Neonatal admission to a specialized care unit and length of stay
Newborn hospital readmission and length of stay
Ambulatory surgery
Proportion of births prior to 280/7 weeks’ gestation
Proportion of births prior to 320/7 weeks’ gestation
Proportion of births ≤7 days
Proportion of births ≤48 hours
Proportion of births ≤24 hours

The following are the safety endpoints (maternal, fetal, and neonatal, as appropriate):
Incidence of reported AEs and serious AEs
Significant changes in vital signs and clinical laboratory tests
Incidence of treatment-limiting toxicities including both clinical and laboratory etiology causing subject to discontinue study treatment
Edinburgh Postnatal Depression Scale
Follow-up amniotic fluid index determined by abdominal ultrasound
Fetal acidosis
Neonatal Apgar scores (at 1 and 5 minutes after birth), growth parameters (weight, length, and head circumference) at birth and at discharge, and documentation of any complications
AEs of special interest
Maternal
Death
Chorioamnionitis and its complications
Placental abruption
Postpartum hemorrhage and/or retained placenta
Pulmonary edema
Fetal
Intrauterine fetal demise
Category II or III fetal heart rate tracing (defined according to American College of Obstetricians and Gynecologists Practice Bulletin 106 [ACOG, 2009])
Fetal inflammatory response syndrome
Neonatal
Neonatal death
Asphyxia
Infections (early onset neonatal sepsis, septic shock, pneumonia, meningitis)
RDS
Hypotension
Intraventricular hemorrhage/periventricular leukomalacia
Bronchopulmonary dysplasia
Neonatal acidosis
Hyperbilirubinemia
Neonatal enterocolitis
Hypoxic ischemic encephalopathy

• Proporzione di nascite prima delle 370/7 settimane di gestazione • Proporzione di nascite al termine (da 370/7 a 416/7 settimane di gestazione) • Durata della degenza ospedaliera neonatale • Proporzione di neonati con eventuali diagnosi dal composito di morbilità e mortalità neonatale determinata fino a 28 giorni dopo EDD (delle 400/7 settimane) (i dettagli per ogni composito sono forniti nella Sezione 6.2.2) • Decesso fetale o neonatale • Sindrome da distress respiratorio (RDS) • Displasia broncopolmonare • Enterocolite necrotizzante o perforazione isolata • Sepsi • Meningite • Retinopatia del prematuro • Emorragia intraventricolare (IVH) • Lesione della sostanza bianca • Emorragia cerebellare .

E.5.2.1

Timepoint(s) of evaluation of this end point

48 hours after IP infusion, then every week till delivery.

48 ore dopo l'infusione dell'IMP, successivamente ogni settimana dopo il parto

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Double dummy

double dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Atosiban

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Israel

Korea, Republic of

Mexico

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

324

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception