Clinical Trials Register

Summary
EudraCT Number:	2007-005103-18
Sponsor's Protocol Code Number:	NC20971
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2008-05-21
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-005103-18

A.3

Full title of the trial

A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of RO4607381 on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS).

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

NC20971

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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	ROCHE
B.1.3.4	Country	Italy
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	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.3.2	Product code	RO4607381
D.3.4	Pharmaceutical form	Film-coated 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.3.9.1	CAS number	211513-37-0
D.3.9.2	Current sponsor code	RO4607381
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	300
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	No
D.3.11.8	Extractive medicinal product	No
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with a documented recent Acute Coronary Syndrome (ACS)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this trial is to evaluate the potential of RO4607381 to reduce cardiovascular morbidity and mortality in stable CHD patients, with a documented recent ACS.

E.2.2

Secondary objectives of the trial

Assessment of the long-term safety profile of RO4607381
Evaluation of the effect of RO4607381 on lipid metabolism and markers of inflammation and oxidation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients recently hospitalized for ACS, and whose residual cardiovascular risk ay benefit from an increase in HDL-C, will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events: Myocardial Infarction A diagnosis of a qualifying MI event will be defined by abnormal levels of troponin (at least one determination >2x ULN or a set of at least two troponin determinations, drawn at least 6 hours apart, with at least one value elevated between 1 and 2 x ULN and demonstrating a rising or falling pattern) and at least one of the following: Symptoms of myocardial ischemia within 48 hours prior to the MI New ECG findings (or presumed new if no prior ECG available) as described below Imaging evidence (eg, echocardiography, radionuclide angiography, singlephoton emission tomography, MRI) of new or presumed new wall motion or perfusion deficit Please note: The preferred biomarker for myocardial necrosis is troponin (I or T). If troponin assays are not available the preferred alternative is CKMB measured by mass assay. When measuring cardiac troponin or CK-MB the ULN should reflect the 99th percentile of distribution in a normal healthy population. Hospitalization for ACS (ECG Abnormalities without Biomarkers): A diagnosis of a qualifying ACS event without increases in cardiac biomarkers will require admission to hospital or emergency room (exceeding 23 hrs) with symptoms presumed to be caused by myocardial ischemia with an accelerating tempo in the prior 48 hrs and/or prolonged (at least 20 min) rest chest discomfort and new ECG findings (or presumed new if no prior ECG available) as described below and at least one of the following: 50% stenosis of an epicardial coronary artery; positive exercise or pharmacologic stress indicating reversible ischemia; or presence of pathologic Q-waves on ECG Examples of New ECG findings include: New or presumed new ST depression > 0.5mm in 2 contiguous leads or T wave inversion > 1mm in leads with predominant R wave or R/S >1 in 2 contiguous leads. New or presumed new ST elevation at the J point in ≥ 2 contiguous leads with the cut-off points: ≥ 0.2mV in men or ≥ 0.15mV in women in leads V2- V3 and/or ≥0.1 mV in other leads or new or presumed new LBBB New tall R wave > 40ms in V1,V2 and R/S ≥ 1 in V1 with concordant positive T-wave in the absence of a conduction defect. New Q waves ≥ 30 ms wide and > 1mm deep in any 2 leads of a contiguous lead grouping or Q wave >20ms or QS complex in leads V2 and V3 (These criteria also apply to silent MI detected during a routine follow-up visit) Etc.

E.4

Principal exclusion criteria

1. Females who are pregnant or breast-feeding 2. Women of child bearing potential (women who are not surgically sterile or post-menopausal defined as amenorrhea for > 12 months or amenorrhea for 6 – 12 months and FSH ≥ 45U/L) 3. Symptomatic (NYHA Class II or greater) congestive heart failure requiring and persisting despite appropriate medical treatment at randomization 4. Severe anemia defined as hemoglobin ≤ 10 g/L at Visit 2 5. Index ACS event presumed due to uncontrolled hypertension and/or systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg by the end of the placebo run-in period despite anti-hypertensive therapy 6. Hemoglobin A1c >10% at Visit 2 7. Patients with clinically apparent liver disease, eg, jaundice, choleastasis, hepatic synthetic impairment, or active hepatitis 8. Hepatic transaminase, alkaline phosphatase or total bilirubin levels >1.5 times the ULN at Visit 2 9. Unexplained creatine phosphokinase levels >3 times the ULN at visit 2 10. Serum creatinine > 2.2 mg/dL at Visit 2 11. Concomitant treatment with niacin, fibrates, bile acid sequestrants, or riminabant. Treatment with ezetimibe or fish oil derivatives is permitted. 12. Concomitant treatment with any drug other than RO4607381 administered for the purpose of increasing levels of HDL-C. 13. Previous exposure to torcetrapib or any other CETP inhibitor as for example MK-859 14. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to the screening. 15. Any clinically significant medical condition that according to the investigator could interfere with the conduct of the study. 16. Patients whose life expectancy is shorter than duration of the trial 17. Presence of any laboratory abnormality performed prior to randomization that is considered by the investigator to be clinically important. 18. Current alcohol or drug abuse or history thereof within 5 years prior to screening. 19. Patients exposed to RO4607381 within the last 12 months before the start of his study 20. Subjects who have received any investigational drug or device within 1 month of visit 1, or who expect to participate in any other investigational drug or device study during the conduct of this trial 21. Unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is the time to first occurrence of any component of the composite event; as adjudicated by the Clinical Event Committee (CEC). Components of the event are: Coronary heart disease death Major coronary events (nonfatal MI, ,hospitalization for ACS [ECG abnormalities without biomarkers] and resuscitated cardiac arrest:) Stroke, fatal or non-fatal, of presumed atherothrombotic etiology

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

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.8.3

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

222

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

Information not present in EudraCT

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

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

Data dell'ultima visita dell'ultimo paziente per completare lo studio, oppure la data di raccolta dell'ultimo parametro, richiesto per l'analisi statistica (risultati chiave di tollerabilita' ed efficacia), il piu' tardivo nell'ordine

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

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.1.3

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

Yes

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 2008-05-21.

Yes

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

pazienti con malattia coronarica cronica con documentata Sindrome Coronarica Acuta recente

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

6700

F.4.2.2

In the whole clinical trial

15600

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

2008-05-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-04-08

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2012-07-06

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