Clinical Trials Register

Summary
EudraCT Number:	2008-005012-41
Sponsor's Protocol Code Number:	CLAF237A23118
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-26
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

Lithuania - SMCA

A.2

EudraCT number

2008-005012-41

A.3

Full title of the trial

A multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of 52 weeks treatment with vildagliptin on left ventricular function in patients with type 2 diabetes and congestive heart failure.

A.3.1

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

Effect of vildagliptin on left ventricular function in patients with type 2 diabetes and congestive heart failure

A.4.1

Sponsor's protocol code number

CLAF237A23118

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 Services AG
B.1.3.4	Country	Switzerland
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 Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services Inc. representative office in Lithuania
B.5.2	Functional name of contact point	Clinical Trial Desk
B.5.3	Address:
B.5.3.1	Street Address	Konstitucijos av.7
B.5.3.2	Town/ city	Vilnius
B.5.3.3	Post code	LT-09308
B.5.3.4	Country	Lithuania
B.5.4	Telephone number	+3705269 1650
B.5.5	Fax number	+3705249 6338
B.5.6	E-mail	DRA.Lithuania@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	Galvus
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	vildagliptin
D.3.2	Product code	LAF237A
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	vildagliptin
D.3.9.1	CAS number	274901-16-5
D.3.9.2	Current sponsor code	LAF237A
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.3.11 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	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

Type 2 Diabetes. Heart failure (NYHA class I-III).

E.1.1.1

Medical condition in easily understood language

Type 2 Diabetes

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10064081
E.1.2	Term	Heart failure NYHA class III
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10064079
E.1.2	Term	Heart failure NYHA class I
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10064080
E.1.2	Term	Heart failure NYHA class II
E.1.2	System Organ Class	10007541 - Cardiac 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 evaluate the effect of vildagliptin on left ventricular function in patients with T2DM and CHF (NYHA class I-III) by showing that vildagliptin is at least not inferior to placebo with respect to change in left ventricular ejection fraction (LVEF) after 52 weeks of treatment.

E.2.2

Secondary objectives of the trial

• To evaluate the overall safety and tolerability of vildagliptin versus placebo in patients with T2DM and CHF (NYHA class I – III) over 52 weeks of treatment with special regards to signs and symptoms of heart failure.
• To evaluate the efficacy of vildagliptin in patients with T2DM and CHF (NYHA class I-III) by assessing the HbA1c reduction with vildagliptin compared to placebo after 16 weeks of treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must give written informed consent before any assessment is performed.
2. Patients 18-85 years old (inclusive) at Visit 1.
3. Patients with T2DM, diagnosed at least 3 months prior to Visit 1, either untreated (defined as not taking anti-diabetic therapy for at least 8 weeks prior to Visit 1) or treated with anti-diabetic therapy (defined as metformin, sulfonylurea, insulin, alpha-glucosidase inhibitors, or glinides as monotherapy or combination therapy for at least 8 weeks prior to Visit 1) and maintaining dietary advice and exercise habits during the full course of the study.
4. Stable dose of anti-diabetic therapy over the past 4 weeks prior to Visit 1 (stable insulin therapy is defined as ± 20% of total daily units) for patients on anti-diabetic treatment.
5. CHF (NYHA Class I, Class II, or Class III) at Visit 1.
• Treatment of heart failure should be according to guidlines (ACC/AHA 2005) and (ESC/EASD2007) and dosage of beta-blockers, angiotensin converting enzyme-inhibitors(ACE Is) or angiotensin receptor blockers (ARBs) should have been stable for one month prior to Visit 1.
6. LVEF < 40% (results must be available at Visit 2, prior to randomization)
7. HbA1c in the range of ≥ 6.5% to 10% at Visit 1.
8. Body Mass Index (BMI) in the range of 22-42 kg/m2, inclusive, at Visit 1.

For detailed inclusion criteria, please refer to the full protocol.

E.4

Principal exclusion criteria

1. Fasting Plasma Glucose (FPG) ≥ 270 mg/dL (15 mmol/L) at Visit 1.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
3. A history of:
• type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly.
• acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.
4. Patients that have been enrolled in a vildagliptin clinical trial or taken other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within 6 months prior to visit 1.
5. Patients taking vildagliptin at any time.
6. Patients taking thiazolidinediones (TZDs). TZDs given up to 12 months prior to Visit 1 are allowed.
7. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study
8. Any of the following within the past 6 months:
• myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor);
• coronary artery bypass surgery or percutaneous coronary intervention
• unstable angina
• stroke
9. Any of the following ECG abnormalities:
• Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation
• second degree AV block (Mobitz 1 and 2); patients with pacemakers are not excluded.
• third degree AV block; patients with pacemakers are not excluded.
• prolonged QTc (> 500 ms)
10. GFR (estimated by Cockcroft-Gault formula) < 30 mL/min at Visit 1.

For detailed exclusion criteria, please refer to the full protocol.

E.5 End points

E.5.1

Primary end point(s)

Evaluate the effect of vildagliptin on left ventricular function in patients
with T2DM and CHF (NYHA class I-III) by showing that vildagliptin is at
least not inferior to placebo with respect to change in left ventricular
ejection fraction (LVEF) after 52 weeks of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks.

E.5.2

Secondary end point(s)

To evaluate the overall safety of vildagliptin versus placebo in patients
with T2DM and CHF (NYHA class I – III) over 52 weeks of treatment
with special regard to signs and symptoms of heart failure.
To evaluate the efficacy of vildagliptin in patients with T2DM and CHF
(NYHA class I-III) by assessing the HbA1c reduction with vildagliptin
compared to placebo after 16 weeks of treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks.

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

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Czech Republic

Denmark

Estonia

Germany

Greece

Guatemala

India

Italy

Latvia

Lithuania

Poland

Romania

Russian Federation

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 the trial is the last visit of the last subject undergoing the trial.

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

F.1.1