Hypercholesterolemia
Conditions
Keywords
Hyperlipidemia
Brief summary
Evaluate the efficacy of combination therapy AEGR-733 plus atorvastatin 20 mg versus monotherapy on serum lipoproteins over 4 and 8 weeks of therapy. The primary efficacy parameter is percent change in LDL-C after 8 weeks of therapy.
Detailed description
Following a 35-day washout of current lipid-lowering medication (if any) and adherence to a low-fat diet, subjects will receive either atorvastatin 20 mg for 8 weeks, OR AEGR-733 2.5 mg + atorvastatin 20 mg for 4 weeks followed by AEGR-733 5 mg + atorvastatin 20 mg for 4 additional weeks. During the entire study, subjects will be instructed to follow a low-fat/low cholesterol diet and limit alcohol consumption to -/\< 1 drink per day.
Interventions
DRUGAtorvastatin
atorvastatin 20 mg tablets, daily dosing, for 8 weeks.
DRUGAEGR-733
2.5 mg AEGR-733 capsules, daily dosing, 4 weeks followed by 5 mg AEGR-733 capsules, daily dosing, 4 weeks
Sponsors
Aegerion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* M/F 18-70 * 0-1 risk factor, mean LDL-C -/\> 160 and -/\< 250 mg/dL (Visit 2 & 3) * 2+ risk factors, mean LDL-C -/\> 130 & -/\< 250 mg/dL (Visit 2 & 3) * Fasting mean TGs -/\< 400 mg/dL * Understanding and compliance of protocol * sign consent
Exclusion criteria
* Females pregnant, lactating, or CBP who have not been using acceptable contraceptive methods over previous 3 months * Uncontrolled hypertension \>180/95 at screening * Hx of chronic renal insufficiency (serum creatinine \> 2.5 mg/dL) * Hx of liver disease or transaminases \> 1.5 X ULN * Positive for Hepatitis B or C * Major surgery within past 3 mos * Cardiac insufficiency defined as functional Class II-Class IV * Hx of malignancy within previous 5 years * Participation in another investigational drug study within past 6 wks * Serious or unstable medical or psychological condition * Regular alcohol use \> 1 drink per day * Regular consumers of grapefruit juice or medications known to be metabolized by CYP 3A4 * Use of other lipid-lowering meds (washout permitted) * Acute CVD * Diabetes Mellitus * Fasting glucose \>110 mg/dL * BMI -/\> 40 kg/m2 * Significant gastrointestinal symptoms such as IBS * Use of fish oils, niacin, herbal wt. loss products (washout permitted)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in LDL-C After 8 Weeks of Therapy | Baseline and 8 weeks of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Baseline and 4 weeks |
Countries
United States
Participant flow
Recruitment details
This study was performed from 12 May 2008 to 29 Aug 2008. A total of 5 medical clinics participated in the study.
Pre-assignment details
5-week run-in period during which patients were to follow a low-fat diet and washout from previous lipid lowering therapies.
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin 20 mg Oral atorvastatin 20 mg for 8 weeks | 23 |
| Atorvastatin 20 mg + Lomitapide Oral atorvastatin 20 mg and lomitapide 2.5 mg for 4 weeks, followed by 4 weeks of atorvastatin 20 mg and lomitapide 5 mg | 21 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
Baseline characteristics
| Characteristic | Atorvastatin 20 mg | Total | Atorvastatin 20 mg + Lomitapide |
|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 6.22 | 58.3 Years STANDARD_DEVIATION 7.09 | 57.8 Years STANDARD_DEVIATION 8.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 36 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 42 Participants | 20 Participants |
| Region of Enrollment United States | 23 Participants | 44 Participants | 21 Participants |
| Sex: Female, Male Female | 13 Participants | 24 Participants | 11 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 23 | 16 / 21 |
| serious Total, serious adverse events | 0 / 23 | 0 / 21 |
Outcome results
Primary
Percent Change in LDL-C After 8 Weeks of Therapy
Time frame: Baseline and 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin 20 mg | Percent Change in LDL-C After 8 Weeks of Therapy | -39.6 Percent Change | Standard Deviation 14.35 |
| Atorvastatin 20 mg + Lomitapide | Percent Change in LDL-C After 8 Weeks of Therapy | -49.9 Percent Change | Standard Deviation 26.78 |
Secondary
Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight.
Time frame: Baseline and 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in TC | -31.3 Percent | Standard Deviation 9.23 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in Apo B | -33.6 Percent | Standard Deviation 10.19 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in HDL-C | 6.7 Percent | Standard Deviation 8.07 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in Apo A-1 | 4.8 Percent | Standard Deviation 7.53 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in TGs | -21.5 Percent | Standard Deviation 18.31 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in hs-CRP | -12.0 Percent | Standard Deviation 43.21 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in non-HDL-C | -39.6 Percent | Standard Deviation 10.78 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in body weight | 0.0 Percent | Standard Deviation 1.38 |
| Atorvastatin 20 mg | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in LDL-C | -42.5 Percent | Standard Deviation 12.7 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in body weight | -0.7 Percent | Standard Deviation 1.49 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in LDL-C | -51.0 Percent | Standard Deviation 18.34 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in TC | -38.1 Percent | Standard Deviation 15.38 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in TGs | -17.8 Percent | Standard Deviation 28.32 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in HDL-C | -1.9 Percent | Standard Deviation 10.73 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in non-HDL-C | -45.8 Percent | Standard Deviation 17.68 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in Apo B | -37.7 Percent | Standard Deviation 17.05 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in Apo A-1 | -7.8 Percent | Standard Deviation 8.85 |
| Atorvastatin 20 mg + Lomitapide | Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. | Change in hs-CRP | 60.5 Percent | Standard Deviation 187.5 |