Clinical Trials Register

Summary
EudraCT Number:	2015-002148-15
Sponsor's Protocol Code Number:	201500214815
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2024-12-16
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2015-002148-15

A.3

Full title of the trial

Pregnancy Outcomes: Effects of Metformin Study (POEM Study) a long term
randomized controlled parallel group study in gestational diabetes mellitus

A.3.1

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

Pregnancy Outcomes: Effects of Metformin Study (POEM Study) a long term
randomized controlled parallel group study in gestational diabetes mellitus

A.3.2

Name or abbreviated title of the trial where available

POEM Study

A.4.1

Sponsor's protocol code number

201500214815

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02947503

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bethesda Diabetes research Center (BDRC)
B.1.3.4	Country	Netherlands
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	Diabetes and Vascular Research Foundation
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bethesda Diabetes research Center
B.5.2	Functional name of contact point	BDRC
B.5.3	Address:
B.5.3.1	Street Address	Dr. G. H. Amshoffweg 1
B.5.3.2	Town/ city	Hoogeveen
B.5.3.3	Post code	7909 AA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	Neder0881296859
B.5.5	Fax number	31528286299
B.5.6	E-mail	POEM@treant.nl

D. IMP Identification
D.IMP: 1
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	metformin HCL TEVA 850 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	metformin HCL TEVA 850 mg
D.3.2	Product code	RVG 26048
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral 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

Gestational diabetes mellitus

Zwangerschapsdiabetes

E.1.1.1

Medical condition in easily understood language

Gestational diabetes mellitus

Zwangerschapsdiabetes

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Main objective: to investigate the effects of an early start of metformin (in GDM) on top of standard of care (versus standard of care alone) on clinically relevant endpoints in mother and child, during pregnancy and delivery. Please, see protocol for details.

E.2.2

Secondary objectives of the trial

Secondary objectives: to investigate the effects of an early start of metformin (in GDM) on top of standard of care (versus standard of care alone) on long term outcomes of mother and child. Please, see protocol for details.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Pregnant women with GDM defined as a FPG ≥ 5,3 mmol/l
and/or an OGTT with a PG ≥ 7,8 mmol/l, two hours after the oral
intake of 75 gram glucose
2. Written informed consent
3. Age 18-45 years
4. Gestational age at inclusion 16-34 weeks
5. HbA1c at inclusion ≤ 48 mmol/mol (6.5% Hb)

E.4

Principal exclusion criteria

1. Diabetes mellitus before pregnancy, except previous GDM
2. Proteinuria (UACR > 35 mg/mmol) at screening (UTI excluded)
3. Malignancy during the last 5 years before inclusion, except non-
melanoma skin cancer
4. Psychiatric and/or mood disorder potentially affecting
compliance of treatment
5. Chronic liver disease and/or ASAT and/or ALAT > 3x ULN
6. Chronic renal failure with a GFR < 45 ml/min/1.73m2
7. Chronic pulmonary failure with hypoxia
8. Significantly uncontrolled hypertension – SBP > 160 mm Hg
despite medical treatment
9. Chronic treatment with oral corticosteroids
10. Intolerance for metformin and/or earlier use of metformin in this
pregnancy
11. Membership of the POEM study group
12. Severe foetal anomaly at inclusion – like major neural tube
and/or cardiac malformation
13. Ruptured membranes
14. Multiple pregnancy
15. Inability to understand or read the Dutch or English language
16. Bariatric surgery in medical history
17. Hyperemesis gravidarum

E.5 End points

E.5.1

Primary end point(s)

Phase A: GDM Outcome Score (= GOS), an ordinal variable (range 0-8) per pregnancy: (1) pregnancy related hypertension, including pre-eclampsia and eclampsia, (2) large for gestational age (LGA) at delivery (neonatal weight > 90th percentile), (3) premature delivery (< 37.0 weeks of gestation), (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia (< 2.6 mmol/l), and (8) admission to the NICU.

E.5.1.1

Timepoint(s) of evaluation of this end point

After Phase A and B

E.5.2

Secondary end point(s)

Phase A: each of these eight endpoints apart is a secondary endpoint.
MOS (maternal outcome score): including Caesarean delivery, Pre-eclampsia/eclampsia/HELLP syndrome/gestational hypertension, Maternal mortality, Postpartum haemorrhage, Thrombosis (in pregnancy and/or childbed).
NOS (neonatal outcome score): including Infant Respiratory Distress Syndrome (IRDS) needing nasal CPAP, optiflow, mechanical ventilation and/or surfactant replacement, stillbirth and neonatal death, preterm birth = birth before 37.0 weeks, dystocia of the shoulder during delivery, instrumental delivery, caesarean delivery, neonatal hypoglycaemia < 2.6 mmol/l, neonatal jaundice needing phototherapy, admission to NICU, Apgar score as a variable, Apgar score < 7 at 5 minutes, congenital anomaly
Maternal weight, weight gain and change in body compostition (impedance)
Maternal glycaemic control: FPG and glucose tolerance
Maternale proteinuria
Maternal insulin rescue and daily dose of insulin after failure of study drug
Acceptability of treatment
Maternal urinary tract infection
Maternal metabolic varibales from venous sampling (please see protocol)
Child: intra-uterine measurements by ultra-sonography
Child: foetal weight at delivery
Neonatal metabolic variables from umbilical cord
Phase B/C: Diabetes & Prediabetes development, Weight development, Hypertension development, thrombotic and CVD incidents, development of any chronic disease
Phase B/C: Growth and weight development, gonadal and gender development, puberty and maturation, eductional and intellectual development

E.5.2.1

Timepoint(s) of evaluation of this end point

after Phase A, B and C

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

QOL

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Phase C: observational extension study without trial medication

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Comparator is standard of care alone, while the intervantion is metfromin + standard of care.

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

End of Trial (EOT) is also 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

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:

500

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children with given consent by parents

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

500

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	NVOG and NIV

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-01

P. End of Trial
P.	End of Trial Status	Ongoing

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