Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Safety & Efficacy of Combination BMS-201038 (AEGR-733) & Ezetimibe vs. Monotherapy in Moderate Hypercholesterolemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00405067
Recruitment Status : Completed
First Posted : November 29, 2006
Results First Posted : March 4, 2014
Last Update Posted : March 4, 2014
Sponsor:
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: BMS-201038 (AEGR-733)
Drug: Ezetimibe
Enrollment 60
Recruitment Details The study was performed from 30 Jun 2006 to 27 Dec 2006. A total of 6 medical clinics participated in the study.
Pre-assignment Details Patients who were previously on a lipid lowering therapy underwent a 4-week washout period.
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description 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. 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. Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Period Title: Overall Study
Started 28 28 29
Completed 24 19 24
Not Completed 4 9 5
Reason Not Completed
Adverse Event             4             9             4
Lost to Follow-up             0             0             1
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy Total
Hide Arm/Group Description 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. 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. Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 28 28 29 85
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants 28 participants 29 participants 85 participants
55.1  (5.7) 57.5  (7.2) 54.7  (9.0) 55.7  (7.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 28 participants 29 participants 85 participants
Female
14
  50.0%
13
  46.4%
18
  62.1%
45
  52.9%
Male
14
  50.0%
15
  53.6%
11
  37.9%
40
  47.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 28 participants 29 participants 85 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  32.1%
6
  21.4%
7
  24.1%
22
  25.9%
White
18
  64.3%
22
  78.6%
22
  75.9%
62
  72.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.6%
0
   0.0%
0
   0.0%
1
   1.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 28 participants 28 participants 29 participants 85 participants
28 28 29 85
1.Primary Outcome
Title Percent Change in LDL-C at 12 Weeks Therapy Compared to Baseline Between Treatments
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-46.2  (23.8) -29.9  (15.3) -19.6  (9.9)
2.Secondary Outcome
Title Percent of Change at 12 Weeks Therapy Compared to Baseline Between Treatments for the Following Parameters: Total Cholesterol (TC)
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-34.4  (18.8) -22.8  (12.3) -12.0  (8.7)
3.Secondary Outcome
Title Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at 12 Weeks as Compared to Baseline.
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-41.3  (22.7) -26.9  (14.6) -17.0  (10.5)
4.Secondary Outcome
Title Percent Change in Tryglycerides (TGs) at 12 Weeks Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-7.0  (36.0) -5.8  (33.6) 2.7  (35.1)
5.Secondary Outcome
Title Percent Change in HDL-C at 12 Weeks Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-9.2  (14.4) -6.2  (10.8) 5.9  (9.6)
6.Secondary Outcome
Title Percent Change in Lipoprotein(a)[Lp(a)]at 12 Weeks as Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 20 18 21
Mean (Standard Deviation)
Unit of Measure: Percent Change
-12.0  (23.7) -11.4  (29.1) 7.5  (24.1)
7.Secondary Outcome
Title Percent Change in Apolipoprotein A1 (Apo A1) at 12 Weeks as Compared to Baseline
Hide Description [Not Specified]
Time Frame baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 18 23
Mean (Standard Deviation)
Unit of Measure: Percent Change
-10.7  (15.8) -8.0  (12.3) 2.3  (9.5)
8.Secondary Outcome
Title Percent Change in Apolipoprotein B (Apo B) at 12 Weeks as Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 18 23
Mean (Standard Deviation)
Unit of Measure: Percent Change
-36.6  (21.7) -23.7  (14.2) -14.5  (10.6)
9.Secondary Outcome
Title Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) at 12 Weeks as Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
40.4  (80.7) 81.3  (337.6) 233.3  (874.9)
10.Secondary Outcome
Title Percent Change in Body Weight at 12 Weeks as Compared to Baseline
Hide Description [Not Specified]
Time Frame Baseline and 12 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description:
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.
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.
Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
Overall Number of Participants Analyzed 24 19 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
-1.4  (2.9) -1.0  (2.2) -0.1  (2.3)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Hide Arm/Group Description 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. 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. Oral ezetimibe 10 mg and lomitapide placebo for 12 weeks.
All-Cause Mortality
Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/28 (0.00%)      1/28 (3.57%)      0/29 (0.00%)    
Cardiac disorders       
Myocardial infarction  0/28 (0.00%)  0 1/28 (3.57%)  1 0/29 (0.00%)  0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Therapy Lomitapide Monotherapy Ezetimibe Monotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/28 (85.71%)      24/28 (85.71%)      15/29 (51.72%)    
Gastrointestinal disorders       
Diarrhoea  9/28 (32.14%)  9 11/28 (39.29%)  11 2/29 (6.90%)  2
Dyspepsia  1/28 (3.57%)  1 4/28 (14.29%)  4 2/29 (6.90%)  2
Nausea  2/28 (7.14%)  2 4/28 (14.29%)  4 1/29 (3.45%)  1
Abdominal Pain  1/28 (3.57%)  1 3/28 (10.71%)  3 2/29 (6.90%)  2
Flatulence  1/28 (3.57%)  1 4/28 (14.29%)  4 0/29 (0.00%)  0
Constipation  1/28 (3.57%)  1 3/28 (10.71%)  3 1/29 (3.45%)  1
Abdominal distention  2/28 (7.14%)  2 1/28 (3.57%)  1 2/29 (6.90%)  2
Vomiting  4/28 (14.29%)  4 1/28 (3.57%)  1 0/29 (0.00%)  0
Abdominal Discomfort  1/28 (3.57%)  1 3/28 (10.71%)  3 0/29 (0.00%)  0
Eructation  1/28 (3.57%)  1 3/28 (10.71%)  3 0/29 (0.00%)  0
Faeces hard  0/28 (0.00%)  0 2/28 (7.14%)  2 0/29 (0.00%)  0
Infections and infestations       
Upper respiratory tract infection  2/28 (7.14%)  2 1/28 (3.57%)  1 1/29 (3.45%)  1
Nasopharyngitis  0/28 (0.00%)  0 0/28 (0.00%)  0 2/29 (6.90%)  2
Investigations       
Alanine aminotransferase increased  5/28 (17.86%)  5 8/28 (28.57%)  8 0/29 (0.00%)  0
Aspartate aminotransferase increased  3/28 (10.71%)  3 7/28 (25.00%)  7 0/29 (0.00%)  0
Liver function test abnormal  3/28 (10.71%)  3 0/28 (0.00%)  0 0/29 (0.00%)  0
Nervous system disorders       
Dizziness  0/28 (0.00%)  0 0/28 (0.00%)  0 2/29 (6.90%)  2
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Aegerion Pharmaceuticals
Phone: 617-500-7867
Layout table for additonal information
Responsible Party: Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00405067    
Other Study ID Numbers: AEGR-733-001
First Submitted: November 28, 2006
First Posted: November 29, 2006
Results First Submitted: January 18, 2013
Results First Posted: March 4, 2014
Last Update Posted: March 4, 2014