Clinical Trials Register

Summary
EudraCT Number:	2016-003694-18
Sponsor's Protocol Code Number:	TM002
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-10-13
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2016-003694-18

A.3

Full title of the trial

A double-blind, randomized, placebo-controlled, multiple-dose, multi-centre safety and efficacy study of co-administration of tesofensine/metoprolol in subjects with Prader-Willi syndrome (PWS) "A 12 weeks open label extension"

Az egyidejűleg alkalmazott tezofenzin/metoprolol kettős vak, randomizált, placebo-kontrollált, többszörös dózist alkalmazó, multicentrikus biztonságossági és hatékonysági vizsgálata Prader-Willi szindrómában (PWS) szenvedő betegeknél "12 hetes, nyílt elrendezésű, kiterjesztett vizsgálat”

A.3.1

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

Safety and efficacy of tesofensine/metoprolol in subjects with Prader-Willi syndrome

A metoprolol/tesofensine biztonságossági és hatékonysági vizsgálata Prader-Willi szindrómában

A.4.1

Sponsor's protocol code number

TM002

A.5.4

Other Identifiers

Name:

n.a.

Number:

n.a.

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	Saniona A/S
B.1.3.4	Country	Denmark
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	Saniona A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Saniona A/S
B.5.2	Functional name of contact point	Clinical & Regulatory department
B.5.3	Address:
B.5.3.1	Street Address	Baltorpvej 154
B.5.3.2	Town/ city	Ballerup
B.5.3.3	Post code	DK 2750
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4520289705
B.5.5	Fax number	+4520289705
B.5.6	E-mail	jd@saniona.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	Tesofensine
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tesofensine
D.3.9.1	CAS number	195875-86-6
D.3.9.2	Current sponsor code	NS2330
D.3.9.3	Other descriptive name	TESOFENSINE
D.3.9.4	EV Substance Code	SUB20754
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tesofensine
D.3.9.1	CAS number	195875-86-6
D.3.9.2	Current sponsor code	NS2330
D.3.9.3	Other descriptive name	TESOFENSINE
D.3.9.4	EV Substance Code	SUB20754
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
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	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	Yes
D.2.1.1.1	Trade name	Metoprololsuccinat "Orion" 25mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	metoprolol
D.3.9.3	Other descriptive name	METOPROLOL SUCCINATE
D.3.9.4	EV Substance Code	SUB03274MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	23750
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

Prader Willi syndrome (PWS)

E.1.1.1

Medical condition in easily understood language

Prader Willi syndrome is genetic condition that affects many parts and organ system of the body.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10036476
E.1.2	Term	Prader-Willi syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The purpose of this study is to investigate the safety and efficacy of co-administration of tesofensine/metoprolol treatment versus placebo in adult and pediatric subjects with Prader-Willi syndrome. The primary objective is to examine the effect of co-administration of tesofensine/metoprolol on body weight in subjects with PWS in an open labeled extension study.

E.2.2

Secondary objectives of the trial

The secondary objectives are:
1. To establish pharmacokinetic profile of tesofensine and metoprolol in subjects with PWS
2. To examine the change in hyperphagia-related behaviour in subjects with PWS by use of the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
3. To examine the effect of co-administration of tesofensine/metoprolol on glycaemic control and lipid profile in subjects with PWS
4. To examine the effect of co-administration of tesofensine/metoprolol on HR and BP in subjects with PWS
5. To examine the effects of co-administration of tesofensine/metoprolol on body composition in subjects with PWS
6. To evaluate overall safety and tolerability of co-administration of the tesofensine/metoprolol in subjects with PWS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient must meet all of the following inclusion criteria in order to be eligible for the study:
All male and female pediatric subjects with confirmed diagnosis of PWS who completed the double blind phase (12 weeks) will be invited to participate in the open label 12 weeksextension phase, if deemed eligible by the Investigators.

E.4

Principal exclusion criteria

If subject/parents decide not to participate in the OLE, subject will finish the study based on the Protocol Amendment 1.4.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this study is percent change from baseline to end of treatment in mean body weight.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 180

E.5.2

Secondary end point(s)

Secondary endpoints include:
1. Steady state concentrations of tesofensine and metoprolol as measured by trough values
2. Uptake and initial plateau concentrations of metoprolol as measured by samples taken 2 and 4 hours after dose administration
3. Change from baseline to end of treatment in total HQCT score
4. Change from baseline to end of treatment in mean body weight (kg)
5. Change from baseline to end of treatment in fat- and fat-free mass (%) by dual X-ray absorptiometry (DXA)
6. Change from baseline to end of treatment in HR (bpm), SBP (mmHg), DBP (mmHg)
7. AEs, clinical labs, ECG
There are additional exploratory endpoints:
1. Change from baseline to end of treatment in FPG, insulin
2. Change from baseline to end of treatment in lipid profile
3. Change from baseline to end of treatment in waist circumference (cm)

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to end of study treatment.

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

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

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

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)

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

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

In the case the subject has legal repr/ caregiver written information sheet will be prepared explaining the role of the legal repr/caregiver. In children subjects the information sheet and ICFs will be prepared as per local legislative requirements.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

When a subject ends the study, either per protocol or before of any reason, he/she will be instructed to immediately contact his/her personal primary care physician to resume to his/her entire PW treatment.

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

2016-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-07-22

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