Cardiovascular Disease
Conditions
Brief summary
This multicenter, double-blind, randomized, placebo-controlled study will evaluate the effect of dalcetrapib 600 mg on artherosclerotic disease progression, lipid profile and biomarker profile and long-term safety profile of dalcetrapib in patients with coronary artery disease. Atherosclerotic disease progression will be measured 1. Coronary Intravascular Ultrasound (IVUS), Quantitative Coronary Angiography 2. Carotid B-Mode Ultrasound Intima Medial Thickness (IMT) and total plaque volume in subjects undergoing coronary angiography who have coronary artery disease (CAD). Patients will be randomized to receive dalcetrapib 600 mg orally once a day or placebo. The anticipated time on study treatment will be 24 months. The target sample size is 800-1000 patients.
Interventions
DRUGDalcetrapib
Dalcetrapib 600 mg orally once daily
DRUGPlacebo
Placebo orally once daily
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients over the age of 18 years * Angiographic evidence of coronary artery disease * Ultrasound evidence of carotid artery disease * Treated appropriately for dyslipidemia
Exclusion criteria
* Previous exposure to any cholesteryl ester transfer protein (CETP) inhibitor or CETP-vaccine within the last 3 months before study start * Previous coronary artery bypass graft surgery (CABG) or probable need for CABG in the next 24 months * Myocardial infarction in the target coronary artery for IVUS between the initial IVUS examination and randomization * Patients who have symptomatic congestive heart failure at baseline (New York Heart Association class III or IV) * Severe anemia * Uncontrolled hypertension * Poorly controlled diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS. | 24 months |
| Rate of Change From Baseline to Study End in Carotid Intima-media Thickness (CIMT) Using B-mode Ultrasound | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography | 24 months |
| Blood Lipids, Lipoproteins | Throughout study, 24 months |
| Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography | Throughout Study, 24 months |
Countries
Canada, Germany, Poland, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalcetrapib Dalcetrapib: Dalcetrapib 600 mg orally once daily | 474 |
| Placebo Placebo: Placebo orally once daily | 462 |
| Total | 936 |
Baseline characteristics
| Characteristic | Dalcetrapib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 8.48 | 60.4 years STANDARD_DEVIATION 8.86 | 60.5 years STANDARD_DEVIATION 8.66 |
| Sex: Female, Male Female | 127 Participants | 108 Participants | 235 Participants |
| Sex: Female, Male Male | 347 Participants | 354 Participants | 701 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 255 / 474 | 199 / 462 |
| serious Total, serious adverse events | 61 / 474 | 63 / 462 |
Outcome results
Primary
Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS. | 0.6 Percent Change Atheroma Volume | Standard Deviation 3.69 |
| Placebo | Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS. | 0.5 Percent Change Atheroma Volume | Standard Deviation 2.01 |
Primary
Rate of Change From Baseline to Study End in Carotid Intima-media Thickness (CIMT) Using B-mode Ultrasound
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Rate of Change From Baseline to Study End in Carotid Intima-media Thickness (CIMT) Using B-mode Ultrasound | 0.003 mm/year | Standard Deviation 0.0588 |
| Placebo | Rate of Change From Baseline to Study End in Carotid Intima-media Thickness (CIMT) Using B-mode Ultrasound | 0.003 mm/year | Standard Deviation 0.0568 |
Secondary
Blood Lipids, Lipoproteins
Time frame: Throughout study, 24 months
Population: Data not collected
Secondary
Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography | -0.1 mm | Standard Deviation 0.18 |
| Placebo | Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography | 0.0 mm | Standard Deviation 0.1 |
Secondary
Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography
Time frame: Throughout Study, 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography | 9.2 Percent Diameter Stenosis | Standard Deviation 20.65 |
| Placebo | Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography | 4.3 Percent Diameter Stenosis | Standard Deviation 14.36 |