Coronary Heart Disease
Conditions
Brief summary
This 2 arm study will investigate the efficacy and safety of RO4607381 in patients with coronary heart disease, or CHD risk equivalent. After a pre-randomization phase of 5-12 weeks, patients will be randomized to receive either RO4607381 (900mg po) or placebo po daily for 24 weeks, with concomitant atorvastatin 10-80mg daily, and changes in cholesterol level and lipoprotein metabolism will be measured. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGdalcetrapib
900mg po daily for 24 weeks
DRUGPlacebo
po daily for 24 weeks
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 75 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-75 years of age; * CHD or CHD risk equivalent; * body weight \<125kg at visit 1.
Exclusion criteria
* recent (within 3 weeks of screening) clinically significant coronary events; * history of statin-associated myopathy, or intolerance to statin; * history of malignancy (except for curatively treated basal cell or squamous cell cancer of the skin) during the 3 years prior to screening; * exposure to RO4607381 in past 12 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change From Baseline in HDL-C | Baseline and Week 24 |
| Percent Change From Baseline in HDL-C | Baseline and Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Mass | Baseline and Weeks 24 |
| Change in Mesenteric Lymph Nodes | Baseline and 48 Weeks |
| Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | Baseline and 48 Weeks |
| Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Activity | Baseline and 48 Weeks |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalcetrapib Dalcetrapib 900mg po daily for 24 weeks
dalcetrapib: 900mg po daily for 24 weeks | 89 |
| Placebo Placebo po daily for 24 weeks
Placebo: po daily for 24 weeks | 46 |
| Total | 135 |
Baseline characteristics
| Characteristic | Dalcetrapib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 7.76 | 60.2 years STANDARD_DEVIATION 7.5 | 60.9 years STANDARD_DEVIATION 7.67 |
| Sex: Female, Male Female | 21 Participants | 8 Participants | 29 Participants |
| Sex: Female, Male Male | 68 Participants | 38 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 89 | 0 / 46 |
| serious Total, serious adverse events | 11 / 89 | 6 / 46 |
Outcome results
Primary
Absolute Change From Baseline in HDL-C
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Absolute Change From Baseline in HDL-C | 12.76 mg/dL | Standard Error 1.17 |
| Placebo | Absolute Change From Baseline in HDL-C | 0.50 mg/dL | Standard Error 1.49 |
Primary
Percent Change From Baseline in HDL-C
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Percent Change From Baseline in HDL-C | 33.40 Percent Change | Standard Error 2.86 |
| Placebo | Percent Change From Baseline in HDL-C | 3.59 Percent Change | Standard Error 3.64 |
Secondary
Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Activity
Time frame: Baseline and 48 Weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Activity | -56.5 percent change in pMOL/mcL/hr | Standard Error 5.09 |
| Placebo | Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Activity | -5.69 percent change in pMOL/mcL/hr | Standard Error 6.67 |
Secondary
Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB)
Time frame: Baseline and 48 Weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | Total Cholesterol | 10.17 Percent change in mg/dL | Standard Error 3.2 |
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | Triglycerides | 0.94 Percent change in mg/dL | Standard Error 8.76 |
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | HDL-C | 33.76 Percent change in mg/dL | Standard Error 4.43 |
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | LDL-C | 4.75 Percent change in mg/dL | Standard Error 4.45 |
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | ApoA1 | 16.43 Percent change in mg/dL | Standard Error 2.54 |
| Dalcetrapib | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | ApoB | 4.98 Percent change in mg/dL | Standard Error 3.83 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | ApoA1 | 8.15 Percent change in mg/dL | Standard Error 3.3 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | Total Cholesterol | 2.67 Percent change in mg/dL | Standard Error 4.22 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | LDL-C | 2.97 Percent change in mg/dL | Standard Error 5.87 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | Triglycerides | 4.11 Percent change in mg/dL | Standard Error 11.63 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | ApoB | 2.48 Percent change in mg/dL | Standard Error 5 |
| Placebo | Change From Baseline in Total Cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C, Apolipoproteins A1 (ApoA1), Apolipoproteins B (ApoB) | HDL-C | 3.69 Percent change in mg/dL | Standard Error 5.81 |
Secondary
Change in Mesenteric Lymph Nodes
Time frame: Baseline and 48 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalcetrapib | Change in Mesenteric Lymph Nodes | Number Decreased in Volume | 6 Number of Nodes |
| Dalcetrapib | Change in Mesenteric Lymph Nodes | Number Increased in Volume | 4 Number of Nodes |
| Placebo | Change in Mesenteric Lymph Nodes | Number Increased in Volume | 11 Number of Nodes |
| Placebo | Change in Mesenteric Lymph Nodes | Number Decreased in Volume | 18 Number of Nodes |
Secondary
Percent Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Mass
Time frame: Baseline and Weeks 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib | Percent Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Mass | 86.45 Percent change | Standard Error 6.3 |
| Placebo | Percent Change From Baseline in Cholesterol Ester Transfer Protein (CETP) Mass | -4.93 Percent change | Standard Error 8.32 |