Clinical Trials Register

Summary
EudraCT Number:	2011-000518-21
Sponsor's Protocol Code Number:	CLMF237ADE02
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:	2011-04-08
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2011-000518-21

A.3

Full title of the trial

Cross-over study to assess the difference in fasting plasma glucose (FPG) between vildagliptin (Galvus®/Eucreas®) and sitagliptin (Januvia®/Janumet®) after two weeks (FPG-VISIT)

A.3.1

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

Comparison of fasting plasma glucose in patients treated with vildagliptin or sitagliptin

A.3.2

Name or abbreviated title of the trial where available

FPG-VISIT

A.4.1

Sponsor's protocol code number

CLMF237ADE02

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	Novartis Pharma GmbH
B.1.3.4	Country	Germany
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	Novartis Pharma GmbH
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	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Project Leader
B.5.3	Address:
B.5.3.1	Street Address	Roonstr. 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	004991127312583
B.5.5	Fax number	004991127315583
B.5.6	E-mail	peter.lenhardt@novartis.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	Yes
D.2.1.1.1	Trade name	Eucreas
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Eucreas
D.3.2	Product code	LMF237
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	VILDAGLIPTIN
D.3.9.1	CAS number	274901-16-5
D.3.9.4	EV Substance Code	SUB25199
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	1000
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	Janumet
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme, Inc.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Janumet
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	SITAGLIPTIN PHOSPHATE MONOHYDRATE
D.3.9.1	CAS number	654671-77-9
D.3.9.3	Other descriptive name	SITAGLIPTIN PHOSPHATE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB25198
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	1000
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

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	13.1
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	10027433 - Metabolism and nutrition disorders

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 assess the difference in FPG between vildagliptin and sitagliptin after two weeks in patients with type 2 diabetes mellitus pre-treated with metformin.

E.2.2

Secondary objectives of the trial

To assess the difference in FPG between vildagliptin and sitagliptin after a missed dose of either drug in patients with type 2 diabetes mellitus on concomitant treatment with metformin.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Type 2 diabetic patients stabilized on metformin monotherapy (stable dose for at least 4 weeks prior to Screening) ≥ 1000 mg/day and ≤ 2000 mg/day.
2. Patients must be diagnosed with type 2 diabetes mellitus at least 3 months prior to screening.
3. HbA1c 7.0 – 9.5% (metformin ≥ 1000 mg/day and < 2000 mg/day) or
HbA1c 6.5 – 9.5% (metformin 2000 mg/day) at screening.
4. FPG 126 – 270 mg/dl (7.0 – 15.0 mmol/L) at screening and at randomization.
5. Male and female patients, age 18 to 85 years of age inclusive.

E.4

Principal exclusion criteria

1. FPG ≥ 270mg/dL (15mmol/L) at Visit 1 and Visit 102.
2. Use of any of the following medications as assessed at Visit 1:
a. use of any antidiabetic medication within the last 12 weeks, except metformin
b. use of weight control products including weight-loss medications in the last 12 weeks.
c. use of oral (≥7 consecutive days) or chronic parenteral or intra-articular corticosteroid treatment within the last 8 weeks. Inhaled or topical steroids without systemic effects will be allowed.
d. treatment with growth hormone within the previous 6 months.
e. treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study.
3. a history or evidence of any of the following at Visit 1:
a. acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including precoma and coma) within the past 6 months.
b. current diagnosis of congestive heart failure (NYHA III or IV).
c. myocardial infarction within the past 6 months.
d. other acute or chronic disease which may cause tissue hypoxic (e.g. respiratory insufficiency, shock) within the past 6 months.
e. coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months.
f. Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months.
g. unstable angina within the past 3 months.
h. sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled).
i. active substance abuse, alcohol abuse and history of alcohol-related diseases within the past 2 years.
j. type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes
k. malignancy of an organ system (other than localized basal cell carcinoma of the skin) treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
l. hepatic disorder
m. acute infections which may affect blood glucose control within the past 4 weeks.
n. Acute conditions with the potential to alter renal function within the past 6 months, such as:
• dehydration,
• severe infection,
• shock,
• intravascular administration of iodinated contrast agents
4. any of the following significant laboratory abnormalities as assessed at Visit 1:
a. clinically significant increase or reduction in thyroid stimulating hormone (TSH) outside of the normal range.
b. clinically significant renal dysfunction: glomerular filtration rate (GFR) <60mL/min/1.73m2 (via MDRD formula).
c. alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeated measurements within 3 working days.
d. total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN confirmed by repeated measurements within 3 working days.
e. positive Hepatitis B surface antigen (HBsAg).
f. positive Hepatitis C virus (HCV) antibody test (anti-HCV).
g. elevated fasting triglycerides (TGs) > 500mg/dL (5.65mmol/L), confirmed by a repeated measurements within 3 working days.
h. clinically significant laboratory abnormalities which, in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study.
5. any of the following electrocardiographic abnormalities at Visit 1:
a. second or third degree atrio-ventricular block without a pacemaker.
b. long QT syndrome or QTc > 500ms.
c. clinically significant electrocardiogram (ECG) abnormalities which, in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study
6. previous or current participation in any vildagliptin clinical study.
7. concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
8. donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks before screening or a blood transfusion within the past 12 weeks before screening or planned regular transfusions during the study period.
9. potentially unreliable, inability to comply with the study procedures or medications, and/or judged by the investigator to be unsuitable for the study.
10. use of an investigative drug within 30 days or 5 half-lives of the drug before screening, whichever is longer.
11. Women of childbearing potential not using hormonal contraceptives with a pearl index < 1, as well as women who are breastfeeding
12. Known sensitivity to study drug(s) or class of study drug(s)
13. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
14. Women
o who are pregnant or breast feeding
o who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is to demonstrate that the FPG after 14 days of treatment with Vildagliptin is superior to the FPG after 14 days of treatment with.

E.5.1.1

Timepoint(s) of evaluation of this end point

14 days

E.5.2

Secondary end point(s)

The secondary endpoint FPG after a missed dose will be analyzed descriptively using graphical methods and tabulations.

E.5.2.1

Timepoint(s) of evaluation of this end point

14 days

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

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.1.6

Cross over

Yes

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

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

LPLV

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	80
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	20
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	100

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

2011-04-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-06-06

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