Clinical Trials Register

Summary
EudraCT Number:	2008-005575-96
Sponsor's Protocol Code Number:	LPL100601
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-11
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2008-005575-96

A.3

Full title of the trial

A Clinical Outcomes Study of Darapladib versus Placebo in
Subjects with Chronic Coronary Heart Disease to Compare the
Incidence of Major Adverse Cardiovascular Events (MACE).

A.3.2

Name or abbreviated title of the trial where available

STABILITY

A.4.1

Sponsor's protocol code number

LPL100601

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	GlaxoSmithKline Research & Development, Ltd
B.1.3.4	Country	United Kingdom
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.3.4	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.3.8	INN - Proposed INN	DARAPLADIB
D.3.9.2	Current sponsor code	SB-480848
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	160
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

coronary heart disease

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	10011099
E.1.2	Term	Coronary disease

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 study is to evaluate clinical efficacy of long-term treatment
with darapladib EC tablets, 160 mg (oral once daily dose) as compared to placebo when
added to standard of care in a chronic CHD patient population on the incidence of first
occurrence of the composite of MACE (i.e., CV death, non-fatal MI, non-fatal stroke).

E.2.2

Secondary objectives of the trial

The secondary objectives are to evaluate the efficacy of darapladib on major and total coronary events (including CHD death, non-fatal MI, urgent and non-urgent coronary
revascularization, or hospitalization for unstable angina), individual components of
MACE and all-cause mortality. Additional safety and efficacy parameters, including
relations to and changes of biomarkers of CV risk, health economic outcomes, and adverse events, will also be evaluated.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

FARMACOCINETICA/FARMACODINAMICA: Versione:3 Data:2008/09/23 Titolo:Sottostudi di farmacocinetica e farmacocinetica/farmacodinamica Obiettivi:E’ stato pianificato che circa il 5-7% dei pazienti inclusi nel programma di sviluppo del farmaco di fase III contribuira` ai dati di farmacocinetica di darapladib.

ALTRI SOTTOSTUDI: Sottostudio di valutazione dell’effetto di darapladib sul livello di progressione dell’albuminuria

E.3

Principal inclusion criteria

1. Signed written informed consent prior to beginning study-related procedures (subject
must understand the aims, investigational procedures and possible consequences of
the study).
2. Male or female aged at least 18 years, inclusive, at screening. Female subjects must
be post-menopausal or using a highly effective method for avoidance of pregnancy
4 The decision to include or exclude women of guidelines or contraindicated in the opinion of the investigator.5
4. Chronic CHD documented by at least one of the following:
a. prior MI (>1 month prior to randomization).6
b. prior coronary revascularization procedure [percutaneous coronary intervention
(PCI) > 1 month prior to randomization or coronary artery bypass graft (CABG)
>3 months prior to randomization].7
c. multivessel CHD involving major epicardial coronary arteries confirmed by
coronary angiography at any time (without revascularization).8
AND
5. At least one of the following additional predictors of CV risk:
a. age &#8805;60 years at randomization.
b. diabetes mellitus requiring pharmacotherapy.
c. HDL-C <40 mg/dL (1.03 mmol/L).
d. smoker (defined as at least 5 cigarettes per day on average) or a previous
smoker (defined as at least 5 cigarettes per day on average when smoking) who
discontinued within the past 3 months.
e. significant renal dysfunction (defin
childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.
3. Current treatment with statin therapy

E.4

Principal exclusion criteria

1. Planned coronary revascularization (PCI or CABG) or any other major surgical
procedure.
2. Current liver disease, known hepatic or biliary abnormalities (with the exception of
Gilbert’s syndrome or asymptomatic gallstones) or evidence of abnormal liver
function tests [total bilirubin or alkaline phosphatase >1.5 x upper limit of normal
(ULN); or ALT or AST >2.5 x ULN or other hepatic abnormalities that in the
opinion of the Investigator would preclude the subject from participation in the
study.
3. Severe renal impairment (eGFR13 <30 mL/min/1.73 m2) or history of nephrectomy
or kidney transplant (regardless of renal function).
4. Current severe heart failure (New York Heart Association class III or IV).
5. Poorly controlled hypertension despite lifestyle modifications and
pharmacotherapy
6. Any life-threatening condition with life expectancy <2 years, other than vascular disease, that might prevent the subject from completing the study (e.g., very severe
chronic airways disease, known human immunodeficiency virus [HIV] positive, or
cancer in the past five years other than non-melanoma skin cancer).
7. Severe asthma that is poorly controlled on pharmacotherapy.
8. Positive pregnancy test (all female subjects of childbearing potential must have a
urine &#946;-human chorionic gonadotropin [hCG] pregnancy test performed at Screening
and/or within 7 days prior to randomization) or is known to be pregnant or lactating.
History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions (Refer to
9. Clinical criteria for diagnosing anaphylaxis), or severe
allergic responses.
10. Alcohol or drug abuse within the past 6 months, or current mental condition
(psychiatric disorder, senility or dementia), which may affect study compliance or
prevent understanding of the aims, investigational procedures or possible
consequences of the study.
11. Current or planned chronic administration of strong oral or injectable cytochrome P-
450 isoenzyme 3A4 (CYP3A4) inhibitors.15
12. Subjects with both parents of Japanese, Chinese, or Korean ancestry must have a
blood sample collected for assessment of Lp-PLA2 activity by the central laboratory
prior to randomization. Those with Lp-PLA2 activity &#8804;10 nmol/min/mL will be
excluded from participation in the study.16
13. Previous exposure to darapladib (SB-480848).
14. Use of another investigational product within 30 days or 5 half-lives (whichever is
the longer) preceding the first dose of darapladib or matching placebo.
15. Currently in a study of an investigational device.
16. Any other reason the investigator deems the subject to be unsuitable for the study

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the time to the first occurrence of any component of the
composite of major adverse cardiovascular events (MACE: CV death, non-fatal MI, or non-fatal stroke) in a chronic CHD population treated with darapladib enteric coated
tablets, 160 mg compared with placebo.
Cardiovascular Death
CV death is defined as death due to documented CV cause. Causes of CV deaths include but are not limited to deaths resulting from stroke, arrhythmia, sudden death
(witnessed or unwitnessed), MI, heart failure, pulmonary embolism, PAD or
complications of a CV procedure. Additionally, deaths not clearly attributable to non-CV
causes will be considered CV deaths.

Acute MI: evidence of myocardial necrosis in a clinical setting consistent with
myocardial ischemia. Under these conditions, any one of the following criteria meets the
diagnosis for MI:
Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at
least one value above the 99th percentile of a normal reference population (URL = upper reference limit) together with evidence of myocardial ischemia with at least
one of the following:
Symptoms of ischemia;
ECG changes indicative of new ischemia
Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by presumably new ST
elevation, or new LBBB, and/or evidence of fresh thrombus by coronary
angiography and/or autopsy, but death occurring before blood samples could be
obtained, or at a time before the appearance of cardiac biomarkers in the blood.
For PCI in patients with normal baseline troponin values, elevations of cardiac biomarkers above the 99th percentile URL are indicative of peri-procedural necrosis.
By convention, increases of biomarkers greater than 3 x 99th URL have been
designated as defining PCI-related myocardial infarction. A subtype related to a documented stent thrombosis is recognized.
For coronary artery bypass grafting (CABG) in patients with normal baseline
troponin values, elevations of cardiac biomarkers above the 99th percentile URL are indicative of peri-procedural myocardial necrosis. By convention, increases of biomarkers greater than 5 x 99th percentile URL plus either new pathological waves or new left bundle branch block, or angiographically documented new graft or
native coronary artery occlusion, or imaging evidence of new loss of viable
myocardium have been designated as defining CABG-related myocardial infarction.
Pathological findings of an acute MI.
Prior MI (i.e., diagnosed post-randomization): Any one of the following criteria meets
the diagnosis for prior myocardial infarction:
Development of new pathological Q waves with or without symptoms.
Imaging evidence of a region of loss of viable myocardium that is thinned and fails
to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormalities).
Pathological findings of a healed or healing MI. Stroke

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

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)

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

basato sulla frequenza degli eventi

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.8.6 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

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

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	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.1.3	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	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	332
F.4.2	For a multinational trial
F.4.2.1	In the EEA	19000
F.4.2.2	In the whole clinical trial	19000

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

2009-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-26

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