Hypercholesterolemia
Conditions
Keywords
cholesterol
Brief summary
The purpose of this study is to test the effectiveness of the study drug, AEGR-733 alone and in combination with the medication, atorvastatin (Lipitor), on cholesterol in volunteers with moderately high cholesterol.
Detailed description
Recent studies suggest more intensive cholesterol lowering treatment for people at very high risk of a heart attack, specifically for patients who have heart disease plus major risk factors. Available medications used alone at even the highest approved doses are not expected to reach these new target recommendations for cholesterol in a large number of subjects. Thus, the development of new medications that can provide additional cholesterol lowering may be beneficial. This study tests the effectiveness of different doses of the study drug, AEGR-733 alone and in combination with the approved cholesterol lowering drug, atorvastatin (Lipitor), on cholesterol. Volunteers will be randomized to one of 6 different study treatments and will take the assigned medication (3 capsules daily) for 8 weeks.
Interventions
DRUGAEGR-733 5 mg
DRUGAEGR-733 10 mg
DRUGPlacebo
DRUGAEGR-733 5 mg + atorvastatin 20 mg
DRUGAEGR-733 10 mg + atorvastatin 20 mg
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
No
Inclusion criteria
1. Men and women between the ages of 18 and 70 years. 2. Elevated LDL cholesterol based on risk factors for cardiovascular disease or presence of cardiovascular disease
Exclusion criteria
1. Women who are pregnant, lactating, planning to become pregnant, or women of childbearing potential who have not successfully been using acceptable contraceptive methods over the previous 3 months, e.g., intrauterine device (IUD) and barrier method plus spermicide. 2. Uncontrolled hypertension 3. History of chronic kidney problems 4. History of liver disease 5. Positive for Hepatitis B or Hepatitis C. 6. Any major surgical procedure occurring less than 3 months ago 7. Cardiac insufficiency 8. History of a malignant cancer (other than basal cell or squamous cell carcinoma of the skin that has been removed) within the previous 5 years. 9. Regular alcohol use \>1 drink per day. 10. Regular consumers of grapefruit juice, or currently taking the following medications: cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone. 11. Use of other cholesterol lowering medications that cannot be stopped. 12. Heart attack or stroke within the previous 6 months 13. Diabetes Mellitus 14. Body mass index (BMI) ≥ 40 kg/m2. 15. Significant gastrointestinal symptoms, such as irritable bowel syndrome. 16. Current use of fish oils, niacin, and herbal weight loss products that cannot be stopped.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in LDL-C at 8 Weeks | Atfer 8 weeks on study drug |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline of Other Lipids | After 8 weeks of study drug |
Countries
United States
Participant flow
Recruitment details
The study was performed from 05 November 2007 to 04 August 2008 at 17 medical clinics within the United States.
Pre-assignment details
Subjects who were previously on a lipid lowering therapy underwent a 5-week washout period. All subjects were on a low-fat diet (\<30% calories from fat) starting 5 weeks prior to study drug treatment and continuing for the duration of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo capsule taken orally once daily | 27 |
| Atorvastatin 20 mg Atorvastatin 20 mg taken orally once daily | 26 |
| AEGR-733 5 mg AEGR-733 5 mg taken orally once daily | 26 |
| AEGR-733 10 mg AEGR-733 10 mg taken orally once daily | 26 |
| AEGR-733 5 mg + Atorvastatin 20 mg One capsule of AEGR-733 5 mg and 1 capsule of Atorvastatin 20 mg taken orally once daily | 26 |
| AEGR-733 10 mg + Atorvastatin 20 mg One capsule of AEGR-733 10 mg and 1 capsule of Atorvastatin 20 mg taken orally once daily | 26 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 9 | 14 | 5 | 16 |
| Overall Study | Removed due to lab value | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | AEGR-733 10 mg + Atorvastatin 20 mg | AEGR-733 5 mg + Atorvastatin 20 mg | AEGR-733 10 mg | AEGR-733 5 mg | Atorvastatin 20 mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 53 Years STANDARD_DEVIATION 11.1 | 54 Years STANDARD_DEVIATION 10 | 53 Years STANDARD_DEVIATION 9.7 | 51 Years STANDARD_DEVIATION 10.1 | 54 Years STANDARD_DEVIATION 11.6 | 56 Years STANDARD_DEVIATION 8.3 | 56 Years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 7 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 150 Participants | 26 Participants | 23 Participants | 23 Participants | 25 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 23 Participants | 3 Participants | 5 Participants | 4 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 127 Participants | 22 Participants | 18 Participants | 21 Participants | 23 Participants | 21 Participants |
| Region of Enrollment United States | 27 participants | 157 participants | 26 participants | 26 participants | 26 participants | 26 participants | 26 participants |
| Sex: Female, Male Female | 13 Participants | 87 Participants | 16 Participants | 10 Participants | 16 Participants | 16 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 70 Participants | 10 Participants | 16 Participants | 10 Participants | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 27 | 15 / 26 | 23 / 26 | 23 / 26 | 21 / 26 | 24 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 1 / 26 | 1 / 26 | 0 / 26 | 0 / 26 |
Outcome results
Primary
Percent Change From Baseline in LDL-C at 8 Weeks
Time frame: Atfer 8 weeks on study drug
Population: Intent To Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in LDL-C at 8 Weeks | 2 Percent Change | Standard Deviation 11.2 |
| Atorvastatin 20 mg | Percent Change From Baseline in LDL-C at 8 Weeks | -42 Percent Change | Standard Deviation 16.4 |
| AEGR-733 5 mg | Percent Change From Baseline in LDL-C at 8 Weeks | -16 Percent Change | Standard Deviation 17.3 |
| AEGR-733 10 mg | Percent Change From Baseline in LDL-C at 8 Weeks | -37 Percent Change | Standard Deviation 23 |
| AEGR-733 5 mg + Atorvastatin 20 mg | Percent Change From Baseline in LDL-C at 8 Weeks | -47 Percent Change | Standard Deviation 19.2 |
| AEGR-733 10 mg + Atorvastatin 20 mg | Percent Change From Baseline in LDL-C at 8 Weeks | -50 Percent Change | Standard Deviation 28 |
Secondary
Percent Change From Baseline of Other Lipids
Time frame: After 8 weeks of study drug
Population: Intent To Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | 0 Percent | Standard Deviation 11 |
| Placebo | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | 2 Percent | Standard Deviation 9.9 |
| Placebo | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | 2 Percent | Standard Deviation 10.3 |
| Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | -34 Percent | Standard Deviation 13 |
| Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | -30 Percent | Standard Deviation 12.4 |
| Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | -38 Percent | Standard Deviation 15.8 |
| AEGR-733 5 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | -17 Percent | Standard Deviation 12.4 |
| AEGR-733 5 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | -18 Percent | Standard Deviation 14.6 |
| AEGR-733 5 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | -19 Percent | Standard Deviation 17.1 |
| AEGR-733 10 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | -36 Percent | Standard Deviation 21.9 |
| AEGR-733 10 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | -33 Percent | Standard Deviation 19 |
| AEGR-733 10 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | -36 Percent | Standard Deviation 26 |
| AEGR-733 5 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | -41 Percent | Standard Deviation 16.9 |
| AEGR-733 5 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | -37 Percent | Standard Deviation 15.3 |
| AEGR-733 5 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | -45 Percent | Standard Deviation 17.7 |
| AEGR-733 10 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total cholesterol | -40 Percent | Standard Deviation 20.7 |
| AEGR-733 10 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in non-HDL-C | -48 Percent | Standard Deviation 24.5 |
| AEGR-733 10 mg + Atorvastatin 20 mg | Percent Change From Baseline of Other Lipids | Percent change from baseline in total Apo B | -46 Percent | Standard Deviation 19.8 |