Clinical Trials Register

Summary
EudraCT Number:	2008-006719-20
Sponsor's Protocol Code Number:	0431-082
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-12-09
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2008-006719-20

A.3

Full title of the trial

TECOS: A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin in Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control

A.3.1

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

TECOS: A Cardiovascular Outcomes Study for Type 2 Diabetes

A.3.2

Name or abbreviated title of the trial where available

TECOS

A.4.1

Sponsor's protocol code number

0431-082

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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
B.1.3.4	Country	United States
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	Merck Sharp & Dhome Corp., a subsidiary of Merck & Co.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MSD Regional Business Support Center GmbH
B.5.2	Functional name of contact point	Dr. Steven Hildemann
B.5.3	Address:
B.5.3.1	Street Address	Lindenplatz 1
B.5.3.2	Town/ city	Haar
B.5.3.3	Post code	85540
B.5.3.4	Country	Germany
B.5.4	Telephone number	+498962731350
B.5.5	Fax number	+4989456655222
B.5.6	E-mail	Steven.Hildemann@essex.de

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	Januvia
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Ltd.
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	Januvia 25 mg film-coated tablets
D.3.2	Product code	MK-0431
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
D.3.9.1	CAS number	790712-60-6
D.3.9.2	Current sponsor code	MK-0431
D.3.9.3	Other descriptive name	Sitagliptin phosphate monohydrate
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	25
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	Januvia
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Ltd.
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	Januvia 100 mg film-coated tablets
D.3.2	Product code	MK-0431
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
D.3.9.1	CAS number	790712-60-6
D.3.9.2	Current sponsor code	MK-0431
D.3.9.3	Other descriptive name	Sitagliptin phosphate monohydrate
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	Film-coated 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 mellitus (T2DM)

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes mellitus

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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 impact of including sitagliptin as part of usual care vs. usual care without sitagliptin on CV outcomes as measured by the time to first event in the primary CV composite endpoint of CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

E.2.2

Secondary objectives of the trial

To compare the impact of including sitagliptin as part of usual care vs. usual care without sitagliptin on:
1 The time to first event in a secondary composite CV endpoint of CV-related death, nonfatal MI, and nonfatal stroke
2 The time to first event for each of the following individual CV
endpoints: confirmed CV-related death, MI (fatal + nonfatal), stroke
(fatal + nonfatal), and unstable angina requiring hospitalization.
3 All-cause mortality
4 Hospital admissions for congestive heart failure as reported by the investigator;
5 Change from baseline in HbA1c over time
6 Change in renal function and albuminuria over time
7 In patients not receiving insulin at baseline, time to initiation of long-term insulin therapy. Long term insulin therapy is defined as a continuous period of insulin use of more than 3 months
8 In patients not receiving insulin at baseline, time to addition of first co-interventional agent
9 Medical resource utilization during the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a. Patient has T2DM with HbA1c of ≥ 6.5% (48 mmol/mol) and ≤ 8.0% (64 mmol/mol) (HbA1c must be documented within 3 months prior to study enrollment) while receiving metformin, pioglitazone, or a sulfonylurea as monotherapy or any dual combination of metformin, pioglitazone, or a sulfonylurea continuously without alteration in dose for at least 3 months OR a stable dose of insulin (±20% of the scheduled total daily insulin dose) either alone or in combination with a stable dose of metformin for at least 3 months
b. Patient is able to see a usual care provider at least twice a year
c. Patient is ≥ 50 years of age with preexisting vascular disease, defined as having any one of the following:
c.1 History of a major clinical manifestation of coronary artery disease (i.e., myocardial infarction, surgical or percutaneous [balloon and/or stent] coronary revascularization procedure, or coronary angiography showing at least one stenosis ≥ 50% in a major epicardial artery or branch vessel);
c.2 Ischemic cerebrovascular disease, including:
c.2.1 History of ischemic stroke. Strokes not known to be hemorrhagic will be allowed as part of this criterion;
c.2.2 History of carotid arterial disease as documented by ≥ 50 % stenosis documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography, with or without symptoms of neurologic deficit.
c.3 Atherosclerotic peripheral arterial disease, as documented by objective evidence such as amputation due to vascular disease, current symptoms of intermittent claudication confirmed by an ankle-brachial pressure index or toe brachial pressure index less than 0.9 or history of surgical or percutaneous revascularization procedure.
d. Female patients agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant.
e. Patient understands the study procedures, alternative treatments available, and the risks involved with the study, and voluntarily agrees to participate by providing written informed consent.
f. Patient agrees to provide permission to obtain all medical records necessary for complete data ascertainment during the follow-up period.

E.4

Principal exclusion criteria

a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis.
b. Patient has a history of ≥2 episodes of severe hypoglycemia during the 12 months prior to enrollment. Severe hypoglycemia (hypoglycemia requiring assistance) refers to instances in which the patient was sufficiently disoriented or incapacitated as to require help from either another individual or from medical personnel (whether or not this assistance was actually provided).
c. Patient has taken an approved or investigational DPP-4 inhibitor agent (e.g., sitagliptin, alogliptin, saxagliptin, or vildagliptin), or GLP-1 analogue (e.g., exenatide, exenatide LAR, or liraglutide), or a thiazolidinedione other than pioglitazone within the past 3 months.
d. Patient has cirrhosis of the liver, as assessed by medical history.
e. Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.
f. Patient has a planned or anticipated revascularization procedure.
g. Pregnancy or planned pregnancy during the trial period.
h. Patient has medical history that indicates a life expectancy of < 2 years or might limit the individual’s ability to take trial treatments for the duration of the study.
i. Patient has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose a risk to the patient, make participation not in the patient’s best interest, confound the results of the study (e.g., if patient cannot comply with requirements of the study), or interfere with the patient’s participation for the full duration of the study.
j. Patient has an estimated GFR (calculated based on serum creatinine via the MDRD formula) of < 30 mL/min/1.73 m2.
k. Patient has a known allergy or intolerance to sitagliptin.
l. Patient has previously been enrolled in this trial.

E.5 End points

E.5.1

Primary end point(s)

Time to first confirmed CV in the primary composite CV endpoint: defined
as the time from randomization to first confirmed event in the primary
composite CV endpoint (CV-related death, nonfatal MI, nonfatal stroke,
or unstable angina requiring hospitalization).

E.5.1.1

Timepoint(s) of evaluation of this end point

CV endpoints are captured at baseline, month 4, month 8, annual visits (month 12, 24, 36, 48, 60, 72), telephone contacts, brief visits (month 18, 30, 42, 54, 66), end of study, and post-study phone contact

E.5.2

Secondary end point(s)

- Time to first confirmed CV event in the secondary composite CV
endpoint: defined as time from randomization to first confirmed event in the secondary composite CV endpoint (CV-related death, nonfatal MI, or nonfatal stroke).
- Time to first confirmed CV event for individual CV endpoints: defined as time from randomization to each of the components of the primary
composite endpoint (CV-related death, MI [fatal + nonfatal], stroke
[fatal +nonfatal], and unstable angina requiring hospitalization).
- Time to all-cause mortality: defined as time from randomization to death due to any cause.
- Time to congestive heart failure: defined as time from randomization to hospital admission for congestive heart failure and treatment with
intravenous diuretics, inotropes, or vasodilator therapy.
- Change from baseline in urinary albumin to creatinine ratio over time.
- Change from baseline in eGFR over time.
- Change from baseline in HbA1c over time.
- Time to initiation of chronic insulin therapy: defined as continuous use
longer than three months in patients not receiving insulin at baseline.
- Time to initiation of first co-interventional agent (i.e., next oral AHA or chronic insulin therapy in patients not receiving insulin at baseline).
- Count of hospitalizations for any reason.

E.5.2.1

Timepoint(s) of evaluation of this end point

(1, 2, 4, 7-9) Endpoints are captured at baseline, month 4, month 8, annual visits (month 12, 24, 36, 48, 60, 72), telephone contacts, brief visits (month 18, 30, 42, 54, 66), end of study, and post-study phone contact

(3) Mortality: Date of death from any cause captured per patient

(5) HbA1c: captured at baseline, month 4, month 8, annual visits (month 12, 24, 36, 48, 60, 72) and end of study

(6) eGFR: captured at baseline, annual visits (month 12, 24, 36, 48, 60, 72), brief visits (month 18, 30, 42, 54, 66), and end of study

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

Yes

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

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

290

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

Australia

Belgium

Brazil

Bulgaria

Canada

Chile

Colombia

Czech Republic

Estonia

European Union

Finland

France

Germany

Hong Kong

Hungary

India

Italy

Korea, Republic of

Latvia

Lithuania

Malaysia

Netherlands

Norway

Spain

Sweden

Israel

Poland

Romania

Russian Federation

Singapore

Slovakia

South Africa

Taiwan

Turkey

United Kingdom

United States

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

6557

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

8200

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

130

F.4.2

For a multinational trial

F.4.2.1

In the EEA

5539

F.4.2.2

In the whole clinical trial

14757

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)

SOC

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

2011-02-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-03-30

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