Clinical Trials Register

Summary
EudraCT Number:	2015-005522-19
Sponsor's Protocol Code Number:	TM001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-23
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

Germany - BfArM

A.2

EudraCT number

2015-005522-19

A.3

Full title of the trial

A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTIPLE-DOSE, TWO-CENTRE, SAFETY AND EFFICACY STUDY OF CO-ADMINISTRATION OF TESOFENSINE/METOPROLOL TREATMENT IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS

A.3.1

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

A STUDY OF CO-ADMINISTRATION OF TESOFENSINE/ METOPROLOL TREATMENT IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS

A.4.1

Sponsor's protocol code number

TM001

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	Mikael S. Thomsen
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	2750
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4523276134
B.5.6	E-mail	mst@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	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.3.9.3	Other descriptive name	TESOFENSINE
D.3.9.4	EV Substance Code	SUB20754
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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	MetoHEXAL
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
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.3.1	Product name	MetoHEXAL
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 TARTRATE
D.3.9.3	Other descriptive name	METOPROLOL TARTRATE
D.3.9.4	EV Substance Code	SUB03275MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetes mellitus type 2

E.1.1.1

Medical condition in easily understood language

Diabetes mellitus type 2

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	100000004861

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 effects of co-administration of tesofensine/ metoprolol treatment vs. placebo on 24-hour mean heart rate

E.2.2

Secondary objectives of the trial

• To compare the effects of co-administration of tesofensine/ metoprolol treatment vs. placebo on systolic and diastolic blood pressure
• To demonstrate a positive effect of co-administration of tesofensine/ metoprolol treatment on:
o body weight
o glycaemic endpoints
o body composition (liver fat)
• To evaluate overall safety and tolerability of co-administration of tesofensine/metoprolol treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Males and females
2.Confirmed diagnosis of T2DM (either by being on anti-diabetic medication or by confirmed or repeated laboratory findings)
3.18-70 years of age
4.Normal BP or well managed hypertension (only if dose of BP medication(s) has been stable for at least two months)
5.Normal lipid profile or well managed dyslipidemia (only if dose of lipid-lowering medication(s) has been stable for at least 2 months)
6. No history of CV disease (as specified in exclusion criteria 7-10) or any other clinically relevant major disease
7.On any dose of metformin stable for at least two months, or
8.On any dose of metformin plus one other oral antidiabetic agent (except TZDs); the other oral agent will be washed out prior to randomization
9.HbA1c ≥7.0%

E.4

Principal exclusion criteria

1.BP > 140/90
2.HbA1c > 8.5%
3. Fasting Plasma glucose > 200 mg/dL at screening
4.HR ≥ 90, <50 bpm
5.BMI < 27 kg/m2
6.Hypersensitivity to tesofensine/metoprolol
7.Heart failure class II or greater according to the New York Heart Association (NYHA) or decompensated heart failure
8.History of myocardial infarction or stroke within 12 months prior to enrolment
9.History of coronary revascularization or angioplasty in the last 12 months prior to enrolment
10.Patients reporting angina in the last 6 months prior to enrolment
11.Treatment with insulin and/or other injectable anti-diabetic medications, or TZDs
12.Any clinically significant cardiac arrhythmia
13.Treatment with calcium channel blockers or beta blockers or their combination
14.Current treatment with medications which should not be co-administered according to the excluded medications list (Appendix I)
15.Concomitant use of monoaminooxidase inhibitors
16.Bulimia or anorexia nervosa
17.Any agent used for weight loss within the last 3 months
18.Patients with history of major depressive disorder or any history of suicide attempt/ideation
19.Patients with family history of severe psychiatric diseases
20.Patients using selective serotonin reuptake inhibitors (SSRIs), antidepressants or anxiolytics.
21.PHQ-9 (Patient Health Questionannire) score ≥ 10 or any score > 0 on question 9
22.Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using highly effective contraceptive methods or postmenopausal women being amenorrheic for less than 1 year and not using highly effective contraceptive methods

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to end of treatment in mean 24 hour HR

E.5.1.1

Timepoint(s) of evaluation of this end point

0-24 h (Baseline on Day -1/1; End of treatment on Day 90/91)

E.5.2

Secondary end point(s)

• Change from baseline to end of treatment in mean SBP
• Change from baseline to end of treatment in mean DBP
• Change from baseline to end of treatment in body weight
• Change from baseline to end of treatment in HbA1c
• Change from baseline to end of treatment in FPG
• Change from baseline to end of treatment in 9-point blood glucose Profile

E.5.2.1

Timepoint(s) of evaluation of this end point

from baseline to end of 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

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

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

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

multiple-dose

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

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 diabetic 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

2016-03-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-15

P. End of Trial
P.	End of Trial Status	Completed

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