Trial Outcomes & Findings for The Safety & Efficacy of Combination BMS-201038 (AEGR-733) & Ezetimibe vs. Monotherapy in Moderate Hypercholesterolemia (NCT NCT00405067)
NCT ID: NCT00405067
Last Updated: 2014-03-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
Baseline and 12 weeks of treatment
Results posted on
2014-03-04
Participant Flow
The study was performed from 30 Jun 2006 to 27 Dec 2006. A total of 6 medical clinics participated in the study.
Patients who were previously on a lipid lowering therapy underwent a 4-week washout period.
Participant milestones
| Measure |
Combination Therapy
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
28
|
28
|
29
|
|
Overall Study
COMPLETED
|
24
|
19
|
24
|
|
Overall Study
NOT COMPLETED
|
4
|
9
|
5
|
Reasons for withdrawal
| Measure |
Combination Therapy
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
9
|
4
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
The Safety & Efficacy of Combination BMS-201038 (AEGR-733) & Ezetimibe vs. Monotherapy in Moderate Hypercholesterolemia
Baseline characteristics by cohort
| Measure |
Combination Therapy
n=28 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=28 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=29 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
Total
n=85 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.1 years
STANDARD_DEVIATION 5.7 • n=93 Participants
|
57.5 years
STANDARD_DEVIATION 7.2 • n=4 Participants
|
54.7 years
STANDARD_DEVIATION 9.0 • n=27 Participants
|
55.7 years
STANDARD_DEVIATION 7.48 • n=483 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
45 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
40 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
22 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
62 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=93 Participants
|
28 participants
n=4 Participants
|
29 participants
n=27 Participants
|
85 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in LDL-C at 12 Weeks Therapy Compared to Baseline Between Treatments
|
-46.2 Percent Change
Standard Deviation 23.8
|
-29.9 Percent Change
Standard Deviation 15.3
|
-19.6 Percent Change
Standard Deviation 9.9
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent of Change at 12 Weeks Therapy Compared to Baseline Between Treatments for the Following Parameters: Total Cholesterol (TC)
|
-34.4 Percent Change
Standard Deviation 18.8
|
-22.8 Percent Change
Standard Deviation 12.3
|
-12.0 Percent Change
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at 12 Weeks as Compared to Baseline.
|
-41.3 Percent Change
Standard Deviation 22.7
|
-26.9 Percent Change
Standard Deviation 14.6
|
-17.0 Percent Change
Standard Deviation 10.5
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Tryglycerides (TGs) at 12 Weeks Compared to Baseline
|
-7.0 Percent Change
Standard Deviation 36.0
|
-5.8 Percent Change
Standard Deviation 33.6
|
2.7 Percent Change
Standard Deviation 35.1
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in HDL-C at 12 Weeks Compared to Baseline
|
-9.2 Percent Change
Standard Deviation 14.4
|
-6.2 Percent Change
Standard Deviation 10.8
|
5.9 Percent Change
Standard Deviation 9.6
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=20 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=18 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=21 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Lipoprotein(a)[Lp(a)]at 12 Weeks as Compared to Baseline
|
-12.0 Percent Change
Standard Deviation 23.7
|
-11.4 Percent Change
Standard Deviation 29.1
|
7.5 Percent Change
Standard Deviation 24.1
|
SECONDARY outcome
Timeframe: baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=18 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=23 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Apolipoprotein A1 (Apo A1) at 12 Weeks as Compared to Baseline
|
-10.7 Percent Change
Standard Deviation 15.8
|
-8.0 Percent Change
Standard Deviation 12.3
|
2.3 Percent Change
Standard Deviation 9.5
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=18 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=23 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Apolipoprotein B (Apo B) at 12 Weeks as Compared to Baseline
|
-36.6 Percent Change
Standard Deviation 21.7
|
-23.7 Percent Change
Standard Deviation 14.2
|
-14.5 Percent Change
Standard Deviation 10.6
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) at 12 Weeks as Compared to Baseline
|
40.4 Percent Change
Standard Deviation 80.7
|
81.3 Percent Change
Standard Deviation 337.6
|
233.3 Percent Change
Standard Deviation 874.9
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks of treatmentOutcome measures
| Measure |
Combination Therapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=19 Participants
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=24 Participants
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Percent Change in Body Weight at 12 Weeks as Compared to Baseline
|
-1.4 Percent Change
Standard Deviation 2.9
|
-1.0 Percent Change
Standard Deviation 2.2
|
-0.1 Percent Change
Standard Deviation 2.3
|
Adverse Events
Combination Therapy
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Lomitapide Monotherapy
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
Ezetimibe Monotherapy
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Combination Therapy
n=28 participants at risk
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=28 participants at risk
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=29 participants at risk
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/28
|
3.6%
1/28 • Number of events 1
|
0.00%
0/29
|
Other adverse events
| Measure |
Combination Therapy
n=28 participants at risk
Oral ezetimibe 10 mg and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Lomitapide Monotherapy
n=28 participants at risk
Oral ezetimibe placebo and lomitapide escalated with an initial oral dose of 5 mg for 4 weeks and then escalated through 2 additional dose levels (7.5 mg and 10 mg) every 4 weeks over an 8-week period.
|
Ezetimibe Monotherapy
n=29 participants at risk
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
32.1%
9/28 • Number of events 9
|
39.3%
11/28 • Number of events 11
|
6.9%
2/29 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
17.9%
5/28 • Number of events 5
|
28.6%
8/28 • Number of events 8
|
0.00%
0/29
|
|
Investigations
Aspartate aminotransferase increased
|
10.7%
3/28 • Number of events 3
|
25.0%
7/28 • Number of events 7
|
0.00%
0/29
|
|
Gastrointestinal disorders
Dyspepsia
|
3.6%
1/28 • Number of events 1
|
14.3%
4/28 • Number of events 4
|
6.9%
2/29 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
7.1%
2/28 • Number of events 2
|
14.3%
4/28 • Number of events 4
|
3.4%
1/29 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Pain
|
3.6%
1/28 • Number of events 1
|
10.7%
3/28 • Number of events 3
|
6.9%
2/29 • Number of events 2
|
|
Gastrointestinal disorders
Flatulence
|
3.6%
1/28 • Number of events 1
|
14.3%
4/28 • Number of events 4
|
0.00%
0/29
|
|
Gastrointestinal disorders
Constipation
|
3.6%
1/28 • Number of events 1
|
10.7%
3/28 • Number of events 3
|
3.4%
1/29 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distention
|
7.1%
2/28 • Number of events 2
|
3.6%
1/28 • Number of events 1
|
6.9%
2/29 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
4/28 • Number of events 4
|
3.6%
1/28 • Number of events 1
|
0.00%
0/29
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
3.6%
1/28 • Number of events 1
|
10.7%
3/28 • Number of events 3
|
0.00%
0/29
|
|
Gastrointestinal disorders
Eructation
|
3.6%
1/28 • Number of events 1
|
10.7%
3/28 • Number of events 3
|
0.00%
0/29
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
2/28 • Number of events 2
|
3.6%
1/28 • Number of events 1
|
3.4%
1/29 • Number of events 1
|
|
Investigations
Liver function test abnormal
|
10.7%
3/28 • Number of events 3
|
0.00%
0/28
|
0.00%
0/29
|
|
Gastrointestinal disorders
Faeces hard
|
0.00%
0/28
|
7.1%
2/28 • Number of events 2
|
0.00%
0/29
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/28
|
0.00%
0/28
|
6.9%
2/29 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/28
|
0.00%
0/28
|
6.9%
2/29 • Number of events 2
|
Additional Information
Chief Medical Officer
Aegerion Pharmaceuticals
Phone: 617-500-7867
Results disclosure agreements
- Principal investigator is a sponsor employee PI can publish after sponsor has 60 days to review the proposed publication. PI is committed to publish the results of the study in a cooperative publication with other investigators prior to individual publication. PI needs sponsor's prior consent to publish confidential information, not to be unreasonably withheld. The PI shall, upon sponsor's request, delete from the publication any confidential information which would prejudice the securing of adequate intellectual property protection.
- Publication restrictions are in place
Restriction type: OTHER