Dyslipidemia
Conditions
Brief summary
This 4 arm study will evaluate the efficacy and safety of RO4607381 when co-administered with pravastatin in patients with low or relatively low HDL-C levels. Patients will be randomised to one of 4 groups to receive either RO4607381 300mg, 600mg or 900mg po daily, or placebo po daily, for 12 weeks.All patients will also receive pravastatin 40mg po daily for 12 weeks.The anticipated time on study treatment is 3 months and the target sample size is 100-500 individuals.
Interventions
DRUGDalcetrapib
300mg po daily for 12 weeks
DRUGPlacebo
po daily for 12 weeks
DRUGPravastatin
40mg po daily for 12 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; * dyslipidemic patients with low or relatively low HDL-C levels during treatment with pravastatin.
Exclusion criteria
* women who are pregnant, breastfeeding, or of child-bearing potential; * morbid obesity; * uncontrolled hypertension; * poorly controlled or insulin-treated diabetes; * high creatinine levels or history of statin-associated myopathy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change From Baseline in HDL-C Level\n | Week 12 |
| Percent Change From Baseline in HDL-C Level\n | 12 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | 12 weeks |
| Percent Change of Fasting Glucose Level | 12 weeks |
| AEs, Lab Parameters, Vital Signs, ECG | Through 9 Months |
| Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | Baseline and at 12 Weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalcetrapib 300mg Pravastatin: 40mg po daily for 12 weeks
dalcetrapib: 300mg po daily for 12 weeks | 76 |
| Dalcetrapib 600mg Pravastatin: 40mg po daily for 12 weeks
dalcetrapib: 600mg po daily for 12 weeks | 68 |
| Dalcetrapib 900mg Pravastatin: 40mg po daily for 12 weeks
dalcetrapib: 900mg po daily for 12 weeks | 74 |
| Placebo Placebo: po daily for 12 weeks
Pravastatin: 40mg po daily for 12 weeks | 74 |
| Total | 292 |
Baseline characteristics
| Characteristic | Dalcetrapib 300mg | Dalcetrapib 600mg | Dalcetrapib 900mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 10.24 | 57.1 years STANDARD_DEVIATION 10.53 | 56.7 years STANDARD_DEVIATION 10.52 | 57.2 years STANDARD_DEVIATION 10.87 | 56.7 years STANDARD_DEVIATION 10.49 |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 17 Participants | 15 Participants | 58 Participants |
| Sex: Female, Male Male | 63 Participants | 55 Participants | 57 Participants | 59 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 76 | 0 / 68 | 0 / 74 | 0 / 74 |
| serious Total, serious adverse events | 2 / 76 | 2 / 68 | 3 / 74 | 2 / 74 |
Outcome results
Primary
Absolute Change From Baseline in HDL-C Level\n
Time frame: Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib 300mg | Absolute Change From Baseline in HDL-C Level\n | 17.18 mg/dL | Standard Error 2.19 |
| Dalcetrapib 600mg | Absolute Change From Baseline in HDL-C Level\n | 31.42 mg/dL | Standard Error 2.29 |
| Dalcetrapib 900mg | Absolute Change From Baseline in HDL-C Level\n | 36.45 mg/dL | Standard Error 2.24 |
| Placebo | Absolute Change From Baseline in HDL-C Level\n | 2.31 mg/dL | Standard Error 2.18 |
Primary
Percent Change From Baseline in HDL-C Level\n
Time frame: 12 Weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib 300mg | Percent Change From Baseline in HDL-C Level\n | 6.58 Percent change in mg/dL | Standard Error 0.84 |
| Dalcetrapib 600mg | Percent Change From Baseline in HDL-C Level\n | 11.90 Percent change in mg/dL | Standard Error 0.88 |
| Dalcetrapib 900mg | Percent Change From Baseline in HDL-C Level\n | 13.92 Percent change in mg/dL | Standard Error 0.86 |
| Placebo | Percent Change From Baseline in HDL-C Level\n | 0.73 Percent change in mg/dL | Standard Error 0.84 |
Secondary
AEs, Lab Parameters, Vital Signs, ECG
Time frame: Through 9 Months
Population: Data not collected
Secondary
Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI
Time frame: 12 weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LDL-C | 8.51 Percent change in mg/dL | Standard Error 2.58 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA2 | 3.82 Percent change in mg/dL | Standard Error 1.23 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-2 | 52.10 Percent change in mg/dL | Standard Error 8.19 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-3 | 11.95 Percent change in mg/dL | Standard Error 1.96 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LpA1 | 15.06 Percent change in mg/dL | Standard Error 3.59 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoB | 2.66 Percent change in mg/dL | Standard Error 1.9 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA1 | 7.03 Percent change in mg/dL | Standard Error 1.39 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-C | 17.18 Percent change in mg/dL | Standard Error 2.19 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Total Cholesterol | 7.08 Percent change in mg/dL | Standard Error 1.45 |
| Dalcetrapib 300mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Triglycerides | -5.95 Percent change in mg/dL | Standard Error 3.93 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Triglycerides | 4.45 Percent change in mg/dL | Standard Error 4.11 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LDL-C | 10.88 Percent change in mg/dL | Standard Error 2.73 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LpA1 | 22.68 Percent change in mg/dL | Standard Error 3.59 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Total Cholesterol | 12.58 Percent change in mg/dL | Standard Error 1.52 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA1 | 13.60 Percent change in mg/dL | Standard Error 1.44 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-2 | 97.40 Percent change in mg/dL | Standard Error 8.82 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoB | 4.62 Percent change in mg/dL | Standard Error 2.01 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-C | 31.42 Percent change in mg/dL | Standard Error 2.29 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-3 | 20.94 Percent change in mg/dL | Standard Error 2.11 |
| Dalcetrapib 600mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA2 | 8.07 Percent change in mg/dL | Standard Error 1.33 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Total Cholesterol | 9.36 Percent change in mg/dL | Standard Error 1.48 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-C | 36.45 Percent change in mg/dL | Standard Error 2.24 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-3 | 23.56 Percent change in mg/dL | Standard Error 2.03 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA1 | 14.90 Percent change in mg/dL | Standard Error 1.4 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Triglycerides | -5.01 Percent change in mg/dL | Standard Error 4.02 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LDL-C | 5.28 Percent change in mg/dL | Standard Error 2.65 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-2 | 121.2 Percent change in mg/dL | Standard Error 8.49 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA2 | 8.36 Percent change in mg/dL | Standard Error 1.28 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoB | -1.64 Percent change in mg/dL | Standard Error 1.95 |
| Dalcetrapib 900mg | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LpA1 | 24.76 Percent change in mg/dL | Standard Error 3.4 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Total Cholesterol | 1.35 Percent change in mg/dL | Standard Error 1.45 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA2 | 0.72 Percent change in mg/dL | Standard Error 1.33 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-3 | 0.68 Percent change in mg/dL | Standard Error 2.12 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-C | 2.31 Percent change in mg/dL | Standard Error 2.18 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LpA1 | 3.32 Percent change in mg/dL | Standard Error 3.81 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoB | -0.71 Percent change in mg/dL | Standard Error 1.98 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | Triglycerides | -4.25 Percent change in mg/dL | Standard Error 3.93 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | HDL-2 | 10.54 Percent change in mg/dL | Standard Error 8.86 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | LDL-C | 3.84 Percent change in mg/dL | Standard Error 2.59 |
| Placebo | Change From Baseline in: Total Cholesterol, Triglycerides, HDL-C, LDL-C, HDL-2, HDL-3, ApoA1, ApoA2, ApoB, LpAI | ApoA1 | 1.01 Percent change in mg/dL | Standard Error 1.46 |
Secondary
Percent Change of Fasting Glucose Level
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalcetrapib 300mg | Percent Change of Fasting Glucose Level | 3.61 Percent change in mg/dL | Standard Error 1.69 |
| Dalcetrapib 600mg | Percent Change of Fasting Glucose Level | 6.03 Percent change in mg/dL | Standard Error 1.79 |
| Dalcetrapib 900mg | Percent Change of Fasting Glucose Level | 5.42 Percent change in mg/dL | Standard Error 1.72 |
| Placebo | Percent Change of Fasting Glucose Level | 3.00 Percent change in mg/dL | Standard Error 1.7 |
Secondary
Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB
Time frame: Baseline and at 12 Weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dalcetrapib 300mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-C/LDL-C | -3.76 Percent Change in Ratio | Standard Error 2.96 |
| Dalcetrapib 300mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-2/HDL-3 | 35.18 Percent Change in Ratio | Standard Error 5.88 |
| Dalcetrapib 300mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | ApoB/ApoA1 | -4.97 Percent Change in Ratio | Standard Error 2.1 |
| Dalcetrapib 600mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-C/LDL-C | -16.0 Percent Change in Ratio | Standard Error 3.2 |
| Dalcetrapib 600mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-2/HDL-3 | 63.40 Percent Change in Ratio | Standard Error 6.33 |
| Dalcetrapib 600mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | ApoB/ApoA1 | -5.79 Percent Change in Ratio | Standard Error 2.19 |
| Dalcetrapib 900mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | ApoB/ApoA1 | -12.7 Percent Change in Ratio | Standard Error 2.11 |
| Dalcetrapib 900mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-C/LDL-C | -19.4 Percent Change in Ratio | Standard Error 3.04 |
| Dalcetrapib 900mg | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-2/HDL-3 | 76.38 Percent Change in Ratio | Standard Error 6.1 |
| Placebo | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-C/LDL-C | 3.09 Percent Change in Ratio | Standard Error 2.95 |
| Placebo | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | HDL-2/HDL-3 | 8.89 Percent Change in Ratio | Standard Error 6.37 |
| Placebo | Ratios of Total HDL-C/LDL-C, HDL-2/HDL-3, ApoA1/ApoB | ApoB/ApoA1 | -1.84 Percent Change in Ratio | Standard Error 2.5 |