Clinical Trials Register

Summary
EudraCT Number:	2004-003000-37
Sponsor's Protocol Code Number:	0653A-807
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:	2005-05-12
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

2004-003000-37

A.3

Full title of the trial

A Double-Blind, Multicenter Study to Assess the LDL-C Lowering of Combination tablets Ezetimibe/Simvastatin (10mg/20mg) and Ezetimibe/Simvastatin (10mg/40mg) compared to Atorvastatin 20mg in Patients with Type II Diabetes.

A.3.2

Name or abbreviated title of the trial where available

Eze/Simva Switch Study in Diabetics

A.4.1

Sponsor's protocol code number

0653A-807

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck & Co. Inc.
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
D.2.1.1.1	Trade name	INEGY 10mg/20mg
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD SHARP & DOHME GMBH, Germany
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	INEGY
D.3.2	Product code	MK0653a
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Ezetimibe/Simvastatin
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	10/20
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Information not present in EudraCT
D.2.1.1.1	Trade name	INEGY 10mg/40mg
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD SHARP & DOHME GMBH, Germany
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	INEGY
D.3.2	Product code	MK0653a
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Ezetimibe/Simvastatin
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	10/40
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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: 3
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	Information not present in EudraCT
D.2.1.1.1	Trade name	LIPITOR 20mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ireland Pharmaceuticals
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	LIPITOR
D.3.2	Product code	LIPITOR
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Atorvastatin
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	20
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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
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

Hypercholesterolemia in patients with Type II Diabetes

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	7.0
E.1.2	Level	LLT
E.1.2	Classification code	10020603

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 determine the additional LDL-C lowering achieved by switching to Ezetimibe/Simvastatin compared to doubling the dose of Atorvastatin.

E.2.2

Secondary objectives of the trial

To determine the effect of Ezetimibe/Simvastatin (10mg/40mg, 10mg/20mg) compared to Atorvastatin 20mg on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, LDL-C/HDL-C ratio, TC/HDL-C ratio and apolipoprotein (apo) B. (2) To further evaluate safety of Ezetimibe/Simvastatin (10mg/40mg, 10mg/20mg) compared to Atorvastatin 20mg.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

a. Patient is currently treated with atorvastatin 10 mg for at least 6 weeks.
b. Patient has Diabetes Mellitus, Type II.
c. Patient has HbA1C of less than or equal to 10.0%.
d. Patient having liver transaminases (ALT, AST) less than or equal to 50% above the upper limit of normal at Visit 1, with no active liver disease, and/or creatine kinase (CK) less than or equal to 50% above the upper limit of normal.

E.4

Principal exclusion criteria

a. Female patient receiving hormone therapy not on a stable dose and regimen for at least 8 weeks prior to Visit 1 or is unwilling to continue the same regimen throughout the study.
b. Patients with alcohol consumption > 14 drink per week. (A drink is: a can of beer, glass of wine, or single measure of spirits.)
c. Patients who are pregnant or lactating.
d. Patients who have been treated with any other investigational drug within 3 months of Visit 1. (If < 3 month, contact the Clinical Monitor for a case-by-case evaluation.)
e. Any condition or situation which, in the opinion of the investigator, might pose a risk to the patient or interfere with participation in the study.
PROHIBITED MEDICAL CONDITIONS:
f. Congestive heart failure defined by NYHA Class III or IV.
g. Myocardial infarction, coronary artery bypass surgery, or angioplasty within 3 months prior to Visit 1.
h. Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm Hg or diastolic > 100 mm Hg at Visit 1.
i. Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e. secondary causes of hyperlipidemia) or secondary hypercholesterolemia due to hypothyroidism, (T4 < 4 g/dL) at Visit 1. Note: Patient with a history of hypothyroidism, who is on stable therapy of thyroid hormone replacement for at least 6 weeks is eligible for enrollment if TSH level is within normal limits at screening Visit 1.
j. Impaired renal function [creatinine  177 mol/L ( 2.0 mg/dL)] or nephrotic syndrome at Visit 1.
k. Disorder of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
l. Patient who is known HIV positive.
m. Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinoma).
n. History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
PROHIBITED CONCOMITANT THERAPIES:
o. Medications that are potent inhibitors of CYP3A4, including cyclosporin, systemic itraconazole or ketoconazole, erythromycin, telithromycin or clarithromycin, nefazodone, protease inhibitors. In addition, patients should not take amiodarone, verapamil, or danazol. Patient is consuming > 1 quart of grapefruit juice/day.
p. Lipid-lowering agents including fish oils, Cholestin, bile-acid sequestrants, other HMG-CoA reductase inhibitors, and niacin (>200 mg/day) taken within 6 weeks and fibrates within 8 weeks prior to randomization at Visit 2 (Day 1).
q. Oral corticosteroids (unless used as replacement therapy for pituitary/adrenal disease and on a stable regimen for at least 6 weeks prior to Visit 1).
r. Patient is not stable on cardiovascular medications, such as beta-blockers, calcium-channel blockers, ACE inhibitors, nitrates, α-adrenergic blockers, thiazide diuretics or anticoagulants (i.e. warfarin), or psyllium, other fiber-based laxatives, and/or an OTC therapy known to affect serum lipid (phytosterol margarine) for at least 6-weeks. Note: Patient will be eligible to participate if on a stable medication regimen for at least 6 weeks prior to Visit 1 and agrees to remain on the same regimen throughout the study.

E.5 End points

E.5.1

Primary end point(s)

6 weeks of treatment for elevated cholesterol only

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

Information not present in EudraCT

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

all patients receive active medication

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

Last visit of last patient is the end of 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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-05-12.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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.4.2

For a multinational trial

F.4.2.1

In the EEA

250

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)

Normal, i.e. patients will receive the usual care (decision up to investigator or general practicioner).

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

2005-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-02-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2005-10-26

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