Clinical Trials Register

Summary
EudraCT Number:	2019-003940-61
Sponsor's Protocol Code Number:	MINT
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2020-10-20
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2019-003940-61

A.3

Full title of the trial

Metformin Intervention in children and adolescents with obesity.
A parallel, three arms, randomized, 6 months, multi-center study with metformin extended release (XR) plus lifestyle or metformin immediate release (IR) plus lifestyle or lifestyle alone.

A.3.1

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

A study with lifestyle intervention and study medication compared to only
lifestyle intervention in children and adolescents with obesity to explore
differences between groups with regard to change in BMI

A.4.1

Sponsor's protocol code number

MINT

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	Uppsala county council
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Healthcare KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Uppsala University Children´s hospital
B.5.2	Functional name of contact point	Obesity Unit f Children&Adolescents
B.5.3	Address:
B.5.3.1	Street Address	Uppsala University Children´s hospital Entrance 95 NBV
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	75185
B.5.3.4	Country	Sweden
B.5.4	Telephone number	460186119495
B.5.6	E-mail	mintstudien@akademiska.se

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	Glucophage XR 500 mg extended release tablet
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Glucophage XR
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.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	Glucophage 500 mg film coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Glucophage 500 mg film coated tablets
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

Children and Adolscents with obesity

E.1.1.1

Medical condition in easily understood language

Children and Adolscents with obesity

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

To compare the effect between metformin extended release (XR) plus lifestyle, and lifestyle alone on the BMI-SDS change, from baseline to the 6 months visit at end of treatment.

E.2.2

Secondary objectives of the trial

1.To compare the effect between metformin immediate release (IR) plus lifestyle, and lifestyle alone on the BMI-SDS change, from baseline to the 6 months visit at end of treatment.
2.To evaluate safety and tolerability
3.To compare the effect between metformin immediate release (IR) plus lifestyle and metformin extended release (XR) plus lifestyle on the BMI-SDS change, from baseline to the 6 months visit at end of treatment.
4.To evaluate the effect of plasma (area under the curve (AUC), PK) and urine concentration of metformin XR and metformin IR on the BMI-SDS change from baseline to the 6 months visit at end of treatment
5 To evaluate the effect of age, sex, puberty, duration of obesity and metformin concentration on BMI-SDS change comparing metformin XR and IR and life style alone from baseline to the 6 months visit at end of treatment
See protocol for more secondary objectives

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent prior to any study-specific procedures.
2. Males or females of age 6 to less than 17 years and 3 months at the time of signing informed consent.
3. Body weight ≥ 40 kg.
4. Obesity (BMI-SDS >2.0) according to WHO.
5. Stable body weight during previous 90 days before screening Visit 1 (< 5kg measured or self-reported weight change).
6. If female of childbearing potential: Not sexually active or usage of adequate anticonception and having negative pregnancy tests. Methods that can achieve a failure rate of less than 1% per year (Pearl index <1), when used consistently and correctly, are considered as highly effective birth control methods.
Such methods include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal.
• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable.
• Intrauterine device (IUD).
• Intrauterine hormone-releasing system (IUS).
• Bilateral tubal occlusion.
• Vasectomised partner
• Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle).

E.4

Principal exclusion criteria

1. Known syndromal obesity (e.g. Prader-Willi syndrome, Bardet-Biedl syndrome or Laurence-Moon syndrome).
2. Pregnancy or lactation.
3. Indigestion-causing diseases
4. Severe gastrointestinal disease, as judged by investigator.
5. Total or partial gastric or small intestine resection.
6. Type 1 diabetes mellitus.
7. Kidney disease or renal dysfunction, acute or chronic (eGFR <60ml/min/1,73m2).
8. Hypo-/hyperthyroidism, unless stable treatment.
9. Severe depression, severe anxiety or other psychiatric disorder referred to or undergoing special treatment, as judged by investigator.
10. Severe sleep apnea, as judged by investigator.
11. Chronic disease, as judged by investigator
12. Metformin treatment within 3 months prior to screening or concomitant medication influencing blood glucose (e.g. metformin and acarbose), influencing other parameters of metabolic syndrome (e.g. orlistat) or interfering with the investigational medicinal product.
13. Steroid treatment (oral or injected).
14. Antidepressants that can lead to weight gain, as judged by investigator.
15. Unstable treatment for neuropsychiatric disorders such as ADHD/ADD, and/or treatment started within 3 months prior to screening visit
16. Known hypersensitivity to metformin or any of the excipients.
17. Language difficulties, impaired mental ability or not willing to understand or comply with the study procedures
18. Participation in another clinical study involving an Investigational Medicinal Product (IMP) within three months prior to screening.
19. Subject from the same household participating in this trial.

E.5 End points

E.5.1

Primary end point(s)

BMI-SDS (according to WHO)

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

E.5.2

Secondary end point(s)

1, 3, 4 BMI-SDS (according to WHO)
2.Adverse Events, vital signs (systolic and diastolic blood pressure (SBP and DBP) and heart rate), physical examination, fP-glucose, ALAT, creatinine, lactate, cobalamin, clinical chemistry, haematology and urine analysis and serum metformin concentration
5.Demographics, tanner stage, and growth chart. Serum and urine concentration of metformin, area under the curve (AUC), PK and BMI-SDS (according to WHO).
7.Glucose and insulin at fasting and during OGTT. Insulin secretion and sensitivity derived from OGTT. HbA1c.
8.Triglycerides, Total cholesterol, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), SBP and DBP.
9.Creatinine, Cystatin C/GFR, Alanine Aminotransferase (ALAT), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LD) and Bilirubin.
10.Hs-CRP
11.IGF1, SHBG, FSH, LH Testosteron and Oestradiol
12.Anthropometrics, waist- and hip circumference (including ratio), and sagittal abdominal diameter (SAD).
Bioimpedance, indirect calorimetry and skin fold measurement will be performed at selected sites
13.Questionnaires: Food Frequency (FFQ), Regular meals, Portion Size, Physical Activity, Medipal®.
14.PedsQL

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Life style session

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-10-20.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-15

P. End of Trial
P.	End of Trial Status	Trial now transitioned

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials