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

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2007-005103-18-GB
• Date of registration: 29/02/2008
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche Ltd.
• Public title: A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of dalcetrapib on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS). - dal-OUTCOMES
• Scientific title: A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of dalcetrapib on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS). - dal-OUTCOMES
• Date of first enrolment: 27/04/2009
• Target sample size: 15600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005103-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Netherlands, Slovakia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients recently hospitalized for ACS (between 4 and 12 weeks after the index event), and whose residual cardiovascular risk may benefit from an increase in HDL-C as assessed by the investigator, will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events:
- Spontaneous Myocardial Infarction
• A diagnosis of a qualifying MI event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or CK-MB mass) with at least one determination >the 99th percentile or upper limits of normal for the laboratory. and at least one of the following described below.
• 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
• Loss of viable myocardium based on imaging evidence of new or presumed new wall motion or perfusion deficit (eg, echocardiography, left ventriculography during cardiac catheterization, radionuclide angiography, single-photon emission tomography, MRI)
Procedure-Related Myocardial Infarction after PCI
Patients experiencing a myocardial infarction after a PCI will also be included in this study. A procedure-related MI after PCI is defined as follows:
Normal biomarkers (eg, CK-MB or troponin I or T) before the procedure and biomarkers after procedure elevated to >3 times the 99th percentile or upper limits of normal for the laboratory.
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)
In addition, the following inclusion criteria apply:
1. Both male and female patients able and willing to give written informed

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) who are not using a highly effective contraceptive method (failure rate less than 1% per year) such as implants, injectables, combined oral contraceptives or hormonal intrauterine devices (IUDs). In addition, a negative serum pregnancy test must be available before starting the run-in period.
3. Symptomatic (NYHA Class II or greater) congestive heart failure requiring appropriate medical treatment and persisting despite such treatment at the end of the run-in period. Patients with NYHA Class II heart failure symptoms may be included if a measurement of left ventricular function is performed and ejection fraction is shown to be >40%.
4. Severe anemia defined as hemoglobin = 10 g/L at the end of the run-in period.
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 the end of the run-in period.
9. Unexplained creatine phosphokinase levels >3 times the ULN at visit 2
10. Serum creatinine > 2.2 mg/dL (194.5 µmol/l) at the end of the run-in period.
11. Concomitant treatment with niacin, fibrates, bile acid sequestrants, or
rimonabant. Treatment with ezetimibe or fish oil derivatives is permitted.
12. Concomitant treatment with any drug other than dalcetrapib 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 dalcetrapib within the last 12 months before the start of
this study and/or have known or suspected hypersensitivity to excipients of trial medication, including placebo (which contains lactose)
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS)
MedDRA version: 9.1 Level: LLT Classification code 10007649 Term: Cardiovascular disorder

Intervention(s)

Product Name: Dalcetrapib
Product Code: RO4607381/F51
Pharmaceutical Form: Film-coated tablet
CAS Number: 211513-37-0
Current Sponsor code: RO4607381
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Secondary Objective: Secondary objectives of this trial are as listed below:
• Assessment of the long-term safety profile of dalcetrapib
• Evaluation of the effect of dalcetrapib on lipid metabolism and markers of
inflammation and oxidation

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

Secondary ID(s)

2007-005103-18-FR

NC20971

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 24/04/2016
• Date Completed: 01/09/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-005103-18/results