FIRST: Safety and Efficacy Study Using ABT-335 (Investigational Drug) in Combination With Atorvastatin, to Study the Effects on Thickening of the Blood Vessel Wall in Patients With Abnormal Lipid (Fat) Levels in the Blood
Study Details
Study Description
Brief Summary
The primary purpose of this study is to test the effect and safety of once daily ABT-335 on the thickness of the lining of the carotid artery (a blood vessel to the brain) in patients with abnormal blood lipids who have optimal levels of low density lipoprotein cholesterol ("bad cholesterol") after taking atorvastatin.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: ABT-335 + Atorvastatin ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. |
Drug: ABT-335
Capsule
Other Names:
Other: Atorvastatin
Capsule
|
Placebo Comparator: Placebo + Atorvastatin Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Drug: Placebo
Capsule
Other: Atorvastatin
Capsule
|
Outcome Measures
Primary Outcome Measures
- Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) [Baseline, 6 months, 12 months, 18 months, and 24 months]
Rate of change (mm/year) from baseline in mean of posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound.
Secondary Outcome Measures
- Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) [Baseline, 6 months, 12 months, 18 months, and 24 months]
Rate of change (mm/year) from baseline in mean of maximal posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound.
- Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) [Baseline, 6 months, 12 months, 18 months, and 24 months]
Rate of change (mm/year) from baseline in composite of mean of the mean posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound.
- Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) [Baseline, 6 months, 12 months, 18 months, and 24 months]
Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound.
- Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) [Baseline, 6 months, 12 months, 18 months, and 24 months]
Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall and anterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with mixed dyslipidemia
-
Qualifying cIMT thickness
Exclusion Criteria:
-
Patients with certain chronic or unstable medical conditions.
-
Patients with unstable dose of medications or receiving coumadin, cyclosporine, or certain other medications
-
Pregnant or lactating women or women intending to become pregnant
-
Patients with diabetes mellitus that is poorly controlled
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Site Reference ID/Investigator# 6747 | Chandler | Arizona | United States | 85225 |
2 | Site Reference ID/Investigator# 7089 | Gilbert | Arizona | United States | 85295 |
3 | Site Reference ID/Investigator# 7097 | Mesa | Arizona | United States | 85206 |
4 | Site Reference ID/Investigator# 26394 | Phoenix | Arizona | United States | 85032 |
5 | Site Reference ID/Investigator# 6848 | Scottsdale | Arizona | United States | 85251 |
6 | Site Reference ID/Investigator# 7059 | Tempe | Arizona | United States | 85282 |
7 | Site Reference ID/Investigator# 7094 | Tempe | Arizona | United States | 85282 |
8 | Site Reference ID/Investigator# 7098 | Tempe | Arizona | United States | 85282 |
9 | Site Reference ID/Investigator# 25082 | Anaheim | California | United States | 92804 |
10 | Site Reference ID/Investigator# 21347 | Corona | California | United States | 92879-3109 |
11 | Site Reference ID/Investigator# 21483 | Garden Grove | California | United States | 92843 |
12 | Site Reference ID/Investigator# 21351 | Huntington Beach | California | United States | 92648 |
13 | Site Reference ID/Investigator# 21346 | Laguna Hills | California | United States | 92653 |
14 | Site Reference ID/Investigator# 21341 | Long Beach | California | United States | 90806 |
15 | Site Reference ID/Investigator# 21342 | Norwalk | California | United States | 90650 |
16 | Site Reference ID/Investigator# 21321 | Santa Ana | California | United States | 92705 |
17 | Site Reference ID/Investigator# 26242 | Tustin | California | United States | 92780 |
18 | Site Reference ID/Investigator# 15283 | Arvada | Colorado | United States | 80005-3927 |
19 | Site Reference ID/Investigator# 7085 | Aurora | Colorado | United States | 80012 |
20 | Site Reference ID/Investigator# 6749 | Denver | Colorado | United States | 80239 |
21 | Site Reference ID/Investigator# 7077 | Denver | Colorado | United States | 80246 |
22 | Site Reference ID/Investigator# 7092 | Golden | Colorado | United States | 80401 |
23 | Site Reference ID/Investigator# 7722 | Littleton | Colorado | United States | 80122 |
24 | Site Reference ID/Investigator# 7721 | Littleton | Colorado | United States | 80127 |
25 | Site Reference ID/Investigator# 11925 | Aventura | Florida | United States | 33180 |
26 | Site Reference ID/Investigator# 15861 | Boynton Beach | Florida | United States | 33472 |
27 | Site Reference ID/Investigator# 14422 | Deerfield Beach | Florida | United States | 33442 |
28 | Site Reference ID/Investigator# 19281 | Delray Beach | Florida | United States | 33445 |
29 | Site Reference ID/Investigator# 20881 | Hollywood | Florida | United States | 33021 |
30 | Site Reference ID/Investigator# 20882 | Kissimmee | Florida | United States | 34741 |
31 | Site Reference ID/Investigator# 19321 | Melbourne | Florida | United States | 32901 |
32 | Site Reference ID/Investigator# 21353 | Melbourne | Florida | United States | 32901 |
33 | Site Reference ID/Investigator# 18503 | Melbourne | Florida | United States | 32935 |
34 | Site Reference ID/Investigator# 18841 | Vero Beach | Florida | United States | 32960 |
35 | Site Reference ID/Investigator# 19961 | Vero Beach | Florida | United States | 32960 |
36 | Site Reference ID/Investigator# 7166 | West Palm Beach | Florida | United States | 33401 |
37 | Site Reference ID/Investigator# 6744 | West Palm Beach | Florida | United States | 33407 |
38 | Site Reference ID/Investigator# 19301 | Atlanta | Georgia | United States | 30308 |
39 | Site Reference ID/Investigator# 7051 | Atlanta | Georgia | United States | 30342-1524 |
40 | Site Reference ID/Investigator# 7109 | Atlanta | Georgia | United States | 30342 |
41 | Site Reference ID/Investigator# 7326 | Dawsonville | Georgia | United States | 30534 |
42 | Site Reference ID/Investigator# 7325 | Decatur | Georgia | United States | 30033 |
43 | Site Reference ID/Investigator# 7057 | Dunwoody | Georgia | United States | 30338 |
44 | Site Reference ID/Investigator# 7101 | Dunwoody | Georgia | United States | 30338 |
45 | Site Reference ID/Investigator# 11324 | Roswell | Georgia | United States | 30076 |
46 | Site Reference ID/Investigator# 6741 | Roswell | Georgia | United States | 30076 |
47 | Site Reference ID/Investigator# 7103 | Suwanee | Georgia | United States | 30024 |
48 | Site Reference ID/Investigator# 10761 | Addison | Illinois | United States | 60101 |
49 | Site Reference ID/Investigator# 6748 | Aurora | Illinois | United States | 60504 |
50 | Site Reference ID/Investigator# 6742 | Aurora | Illinois | United States | 60506 |
51 | Site Reference ID/Investigator# 7128 | Belleville | Illinois | United States | 62220-1986 |
52 | Site Reference ID/Investigator# 7069 | Chicago | Illinois | United States | 60607 |
53 | Site Reference ID/Investigator# 6849 | Chicago | Illinois | United States | 60612-9985 |
54 | Site Reference ID/Investigator# 6867 | Chicago | Illinois | United States | 60612 |
55 | Site Reference ID/Investigator# 6751 | Chicago | Illinois | United States | 60616 |
56 | Site Reference ID/Investigator# 6847 | Chicago | Illinois | United States | 60631 |
57 | Site Reference ID/Investigator# 7049 | Chicago | Illinois | United States | 60654 |
58 | Site Reference ID/Investigator# 7093 | Gurnee | Illinois | United States | 60031 |
59 | Site Reference ID/Investigator# 6746 | Hazel Crest | Illinois | United States | 60429 |
60 | Site Reference ID/Investigator# 6743 | Melrose Park | Illinois | United States | 60160 |
61 | Site Reference ID/Investigator# 7090 | Naperville | Illinois | United States | 60564 |
62 | Site Reference ID/Investigator# 6750 | Oak Brook | Illinois | United States | 60523 |
63 | Site Reference ID/Investigator# 6788 | Oak Park | Illinois | United States | 60304 |
64 | Site Reference ID/Investigator# 6927 | Vernon Hills | Illinois | United States | 60061 |
65 | Site Reference ID/Investigator# 7076 | Erlanger | Kentucky | United States | 41018 |
66 | Site Reference ID/Investigator# 8103 | Bloomington | Minnesota | United States | 55420 |
67 | Site Reference ID/Investigator# 15121 | Brooklyn Center | Minnesota | United States | 55430 |
68 | Site Reference ID/Investigator# 7050 | Edina | Minnesota | United States | 55435 |
69 | Site Reference ID/Investigator# 7084 | Edina | Minnesota | United States | 55435 |
70 | Site Reference ID/Investigator# 6860 | Saint Louis | Missouri | United States | 63110 |
71 | Site Reference ID/Investigator# 13182 | Saint Louis | Missouri | United States | 63117 |
72 | Site Reference ID/Investigator# 14423 | Saint Louis | Missouri | United States | 63128 |
73 | Site Reference ID/Investigator# 14541 | Saint Louis | Missouri | United States | 63141-6399 |
74 | Site Reference ID/Investigator# 6740 | Saint Louis | Missouri | United States | 63141 |
75 | Site Reference ID/Investigator# 7053 | Saint Louis | Missouri | United States | 63141 |
76 | Site Reference ID/Investigator# 6784 | Saint Peters | Missouri | United States | 63376 |
77 | Site Reference ID/Investigator# 7063 | Henderson | Nevada | United States | 89014 |
78 | Site Reference ID/Investigator# 7070 | Henderson | Nevada | United States | 89052 |
79 | Site Reference ID/Investigator# 7106 | Las Vegas | Nevada | United States | 89104 |
80 | Site Reference ID/Investigator# 7518 | Las Vegas | Nevada | United States | 89106 |
81 | Site Reference ID/Investigator# 7119 | Las Vegas | Nevada | United States | 89146 |
82 | Site Reference ID/Investigator# 7129 | Las Vegas | Nevada | United States | 89148 |
83 | Site Reference ID/Investigator# 7071 | Cincinnati | Ohio | United States | 45212 |
84 | Site Reference ID/Investigator# 7100 | Cincinnati | Ohio | United States | 45219 |
85 | Site Reference ID/Investigator# 14321 | Cincinnati | Ohio | United States | 45224 |
86 | Site Reference ID/Investigator# 21355 | Cincinnati | Ohio | United States | 45245 |
87 | Site Reference ID/Investigator# 7074 | Cincinnati | Ohio | United States | 45246 |
88 | Site Reference ID/Investigator# 7065 | Cincinnati | Ohio | United States | 45249 |
89 | Site Reference ID/Investigator# 7075 | Dayton | Ohio | United States | 45439 |
90 | Site Reference ID/Investigator# 24802 | Kettering | Ohio | United States | 45429 |
91 | Site Reference ID/Investigator# 7068 | Mason | Ohio | United States | 45040 |
92 | Site Reference ID/Investigator# 7104 | Bellaire | Texas | United States | 77401 |
93 | Site Reference ID/Investigator# 7060 | Carrollton | Texas | United States | 75006-5810 |
94 | Site Reference ID/Investigator# 15282 | Dallas | Texas | United States | 75230 |
95 | Site Reference ID/Investigator# 6745 | Dallas | Texas | United States | 75231 |
96 | Site Reference ID/Investigator# 7083 | Dallas | Texas | United States | 75231 |
97 | Site Reference ID/Investigator# 7127 | Dallas | Texas | United States | 75231 |
98 | Site Reference ID/Investigator# 7110 | Dallas | Texas | United States | 75251 |
99 | Site Reference ID/Investigator# 21356 | Deer Park | Texas | United States | 77536 |
100 | Site Reference ID/Investigator# 11923 | Fort Worth | Texas | United States | 76116 |
101 | Site Reference ID/Investigator# 7321 | Houston | Texas | United States | 77002 |
102 | Site Reference ID/Investigator# 21354 | Houston | Texas | United States | 77024 |
103 | Site Reference ID/Investigator# 21358 | Houston | Texas | United States | 77030 |
104 | Site Reference ID/Investigator# 26482 | Houston | Texas | United States | 77030 |
105 | Site Reference ID/Investigator# 7079 | Houston | Texas | United States | 77030 |
106 | Site Reference ID/Investigator# 7096 | Houston | Texas | United States | 77030 |
107 | Site Reference ID/Investigator# 7126 | Houston | Texas | United States | 77036 |
108 | Site Reference ID/Investigator# 8186 | Houston | Texas | United States | 77036 |
109 | Site Reference ID/Investigator# 11323 | Houston | Texas | United States | 77074 |
110 | Site Reference ID/Investigator# 7130 | Houston | Texas | United States | 77081 |
111 | Site Reference ID/Investigator# 11924 | Irving | Texas | United States | 75039 |
112 | Site Reference ID/Investigator# 13863 | Irving | Texas | United States | 75061 |
113 | Site Reference ID/Investigator# 7099 | McKinney | Texas | United States | 75069 |
114 | Site Reference ID/Investigator# 19121 | New Braunfels | Texas | United States | 78130 |
115 | Site Reference ID/Investigator# 26244 | Pearland | Texas | United States | 77584 |
116 | Site Reference ID/Investigator# 7105 | Plano | Texas | United States | 75024 |
117 | Site Reference ID/Investigator# 7061 | San Antonio | Texas | United States | 78205 |
118 | Site Reference ID/Investigator# 7320 | San Antonio | Texas | United States | 78215 |
119 | Site Reference ID/Investigator# 7914 | San Antonio | Texas | United States | 78218 |
120 | Site Reference ID/Investigator# 7058 | San Antonio | Texas | United States | 78229-4801 |
121 | Site Reference ID/Investigator# 18402 | San Antonio | Texas | United States | 78229 |
122 | Site Reference ID/Investigator# 7052 | San Antonio | Texas | United States | 78229 |
123 | Site Reference ID/Investigator# 7062 | San Antonio | Texas | United States | 78229 |
124 | Site Reference ID/Investigator# 22947 | San Antonio | Texas | United States | 78238-1434 |
Sponsors and Collaborators
- AbbVie (prior sponsor, Abbott)
Investigators
- Study Director: Maureen Kelly, MD, AbbVie
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- M10-158
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Period Title: Overall Study | ||
STARTED | 340 | 342 |
Treated | 337 | 339 |
COMPLETED | 225 | 240 |
NOT COMPLETED | 115 | 102 |
Baseline Characteristics
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin | Total |
---|---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. | Total of all reporting groups |
Overall Participants | 337 | 339 | 676 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
60.8
(8.71)
|
60.7
(8.79)
|
60.8
(8.75)
|
Sex: Female, Male (Count of Participants) | |||
Female |
109
32.3%
|
109
32.2%
|
218
32.2%
|
Male |
228
67.7%
|
230
67.8%
|
458
67.8%
|
Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [mg/dL] |
84.0
(21.30)
|
84.5
(20.47)
|
84.3
(20.88)
|
Triglycerides (mg/dL) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [mg/dL] |
226.3
(110.01)
|
228.7
(127.06)
|
227.5
(118.78)
|
Posterior-wall Carotid Intima-media (cIMT) Thickness (mm) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [mm] |
0.76
(0.10)
|
0.78
(0.12)
|
0.77
(0.11)
|
Outcome Measures
Title | Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) |
---|---|
Description | Rate of change (mm/year) from baseline in mean of posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound. |
Time Frame | Baseline, 6 months, 12 months, 18 months, and 24 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants who had both a baseline value and at least 1 postbaseline value for that parameter. |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Measure Participants | 281 | 291 |
Mean (Standard Error) [mm/year] |
-0.006
(0.0037)
|
0.000
(0.0036)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ABT-335 + Atorvastatin, Placebo + Atorvastatin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.220 |
Comments | ||
Method | Repeated measures linear mixed model | |
Comments | Fixed effects for baseline cIMT, baseline atorvastatin dose, central imaging site, treatment group, time; interaction between treatment group and time | |
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.006 | |
Confidence Interval |
(2-Sided) 95% -0.016 to 0.004 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) |
---|---|
Description | Rate of change (mm/year) from baseline in mean of maximal posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound. |
Time Frame | Baseline, 6 months, 12 months, 18 months, and 24 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter. |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Measure Participants | 281 | 291 |
Mean (Standard Error) [mm/year] |
-0.005
(0.0047)
|
-0.003
(0.0046)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ABT-335 + Atorvastatin, Placebo + Atorvastatin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.813 |
Comments | ||
Method | Repeated measures linear mixed model | |
Comments | Fixed effects for baseline atorvastatin dose, imaging site, treatment, time; interaction between treatment group and time; baseline cIMT as covariate. | |
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.002 | |
Confidence Interval |
(2-Sided) 95% -0.014 to 0.011 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) |
---|---|
Description | Rate of change (mm/year) from baseline in composite of mean of the mean posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. |
Time Frame | Baseline, 6 months, 12 months, 18 months, and 24 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 3 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 3 or more segments matched the segments at baseline and at 2 years. |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Measure Participants | 138 | 133 |
Mean (Standard Error) [mm/year] |
-0.010
(0.0039)
|
-0.004
(0.0041)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ABT-335 + Atorvastatin, Placebo + Atorvastatin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.249 |
Comments | ||
Method | Repeated measures linear mixed model | |
Comments | Fixed effects for baseline atorvastatin dose, imaging site, treatment, time; interaction between treatment group and time; baseline IMT as covariate | |
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.007 | |
Confidence Interval |
(2-Sided) 95% -0.018 to 0.005 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) |
---|---|
Description | Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. |
Time Frame | Baseline, 6 months, 12 months, 18 months, and 24 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 3 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 3 or more segments matched the segments at baseline and at 2 years. |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Measure Participants | 138 | 133 |
Mean (Standard Error) [mm/year] |
-0.014
(0.0053)
|
-0.008
(0.0056)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ABT-335 + Atorvastatin, Placebo + Atorvastatin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.487 |
Comments | ||
Method | Repeated measures linear mixed model | |
Comments | Fixed effects for baseline atorvastatin dose, imaging site, treatment, time; interaction between treatment group and time; baseline IMT as covariate | |
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.005 | |
Confidence Interval |
(2-Sided) 95% -0.020 to 0.010 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) |
---|---|
Description | Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall and anterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. |
Time Frame | Baseline, 6 months, 12 months, 18 months, and 24 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 6 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 6 or more segments matched the segments at baseline and at 2 years. |
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin |
---|---|---|
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. |
Measure Participants | 67 | 66 |
Mean (Standard Error) [mm/year] |
-0.003
(0.0070)
|
-0.019
(0.0067)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ABT-335 + Atorvastatin, Placebo + Atorvastatin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.112 |
Comments | ||
Method | Repeated measures linear mixed model | |
Comments | Fixed effects for baseline atorvastatin dose, imaging site, treatment, time; interaction between treatment group and time; baseline IMT as covariate | |
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | 0.016 | |
Confidence Interval |
(2-Sided) 95% -0.004 to 0.035 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | AEs that occurred on or after the first dose of study drug through 30 days after last dose of study drug (up to 25 months). | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | ABT-335 + Atorvastatin | Placebo + Atorvastatin | ||
Arm/Group Description | ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Placebo and atorvastatin (up to 40 mg) once daily for 2 years. | ||
All Cause Mortality |
||||
ABT-335 + Atorvastatin | Placebo + Atorvastatin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
ABT-335 + Atorvastatin | Placebo + Atorvastatin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 58/337 (17.2%) | 66/339 (19.5%) | ||
Blood and lymphatic system disorders | ||||
COAGULOPATHY | 1/337 (0.3%) | 0/339 (0%) | ||
Cardiac disorders | ||||
ACUTE CORONARY SYNDROME | 1/337 (0.3%) | 0/339 (0%) | ||
ACUTE MYOCARDIAL INFARCTION | 2/337 (0.6%) | 1/339 (0.3%) | ||
ANGINA PECTORIS | 0/337 (0%) | 1/339 (0.3%) | ||
ANGINA UNSTABLE | 1/337 (0.3%) | 0/339 (0%) | ||
ATRIAL FIBRILLATION | 0/337 (0%) | 1/339 (0.3%) | ||
ATRIOVENTRICULAR BLOCK COMPLETE | 1/337 (0.3%) | 1/339 (0.3%) | ||
CARDIAC FAILURE | 0/337 (0%) | 1/339 (0.3%) | ||
CARDIAC FAILURE CONGESTIVE | 2/337 (0.6%) | 1/339 (0.3%) | ||
CORONARY ARTERY DISEASE | 6/337 (1.8%) | 5/339 (1.5%) | ||
CORONARY ARTERY STENOSIS | 0/337 (0%) | 2/339 (0.6%) | ||
DIASTOLIC DYSFUNCTION | 0/337 (0%) | 1/339 (0.3%) | ||
EXTRASYSTOLES | 1/337 (0.3%) | 0/339 (0%) | ||
ISCHAEMIC CARDIOMYOPATHY | 0/337 (0%) | 1/339 (0.3%) | ||
MYOCARDIAL INFARCTION | 3/337 (0.9%) | 1/339 (0.3%) | ||
MYOCARDIAL ISCHAEMIA | 0/337 (0%) | 1/339 (0.3%) | ||
PERICARDITIS | 0/337 (0%) | 1/339 (0.3%) | ||
SUPRAVENTRICULAR TACHYCARDIA | 1/337 (0.3%) | 0/339 (0%) | ||
TACHYARRHYTHMIA | 1/337 (0.3%) | 0/339 (0%) | ||
VENTRICULAR TACHYCARDIA | 1/337 (0.3%) | 0/339 (0%) | ||
WOLFF-PARKINSON-WHITE SYNDROME | 0/337 (0%) | 1/339 (0.3%) | ||
Ear and labyrinth disorders | ||||
VERTIGO | 2/337 (0.6%) | 1/339 (0.3%) | ||
VESTIBULAR DISORDER | 1/337 (0.3%) | 0/339 (0%) | ||
Eye disorders | ||||
RETINAL HAEMORRHAGE | 0/337 (0%) | 1/339 (0.3%) | ||
Gastrointestinal disorders | ||||
ABDOMINAL HERNIA | 0/337 (0%) | 1/339 (0.3%) | ||
COLITIS ISCHAEMIC | 1/337 (0.3%) | 0/339 (0%) | ||
DIARRHOEA | 1/337 (0.3%) | 0/339 (0%) | ||
DIVERTICULUM INTESTINAL HAEMORRHAGIC | 1/337 (0.3%) | 0/339 (0%) | ||
GASTROINTESTINAL HAEMORRHAGE | 1/337 (0.3%) | 1/339 (0.3%) | ||
GASTROOESOPHAGEAL REFLUX DISEASE | 1/337 (0.3%) | 1/339 (0.3%) | ||
INGUINAL HERNIA | 1/337 (0.3%) | 0/339 (0%) | ||
LOWER GASTROINTESTINAL HAEMORRHAGE | 0/337 (0%) | 1/339 (0.3%) | ||
NAUSEA | 1/337 (0.3%) | 0/339 (0%) | ||
PANCREATITIS ACUTE | 1/337 (0.3%) | 0/339 (0%) | ||
SMALL INTESTINAL OBSTRUCTION | 1/337 (0.3%) | 0/339 (0%) | ||
VOMITING | 1/337 (0.3%) | 0/339 (0%) | ||
General disorders | ||||
CHEST PAIN | 1/337 (0.3%) | 1/339 (0.3%) | ||
MEDICAL DEVICE COMPLICATION | 1/337 (0.3%) | 0/339 (0%) | ||
NON-CARDIAC CHEST PAIN | 4/337 (1.2%) | 3/339 (0.9%) | ||
Hepatobiliary disorders | ||||
CHOLECYSTITIS | 1/337 (0.3%) | 1/339 (0.3%) | ||
CHOLECYSTITIS ACUTE | 1/337 (0.3%) | 0/339 (0%) | ||
CHOLELITHIASIS | 0/337 (0%) | 1/339 (0.3%) | ||
Infections and infestations | ||||
ABSCESS | 0/337 (0%) | 1/339 (0.3%) | ||
ARTHRITIS INFECTIVE | 1/337 (0.3%) | 0/339 (0%) | ||
BRONCHITIS | 0/337 (0%) | 1/339 (0.3%) | ||
CELLULITIS | 1/337 (0.3%) | 0/339 (0%) | ||
CLOSTRIDIAL INFECTION | 1/337 (0.3%) | 0/339 (0%) | ||
DIVERTICULITIS | 2/337 (0.6%) | 0/339 (0%) | ||
PNEUMONIA | 4/337 (1.2%) | 3/339 (0.9%) | ||
PYELONEPHRITIS | 1/337 (0.3%) | 0/339 (0%) | ||
SIALOADENITIS | 1/337 (0.3%) | 0/339 (0%) | ||
STAPHYLOCOCCAL INFECTION | 0/337 (0%) | 1/339 (0.3%) | ||
STAPHYLOCOCCAL SEPSIS | 0/337 (0%) | 1/339 (0.3%) | ||
Injury, poisoning and procedural complications | ||||
ANKLE FRACTURE | 2/337 (0.6%) | 2/339 (0.6%) | ||
FOOT FRACTURE | 1/337 (0.3%) | 0/339 (0%) | ||
HEAD INJURY | 0/337 (0%) | 1/339 (0.3%) | ||
HUMERUS FRACTURE | 0/337 (0%) | 1/339 (0.3%) | ||
JAW FRACTURE | 0/337 (0%) | 1/339 (0.3%) | ||
MENISCUS LESION | 0/337 (0%) | 1/339 (0.3%) | ||
MULTIPLE INJURIES | 1/337 (0.3%) | 0/339 (0%) | ||
MUSCLE RUPTURE | 0/337 (0%) | 1/339 (0.3%) | ||
ROAD TRAFFIC ACCIDENT | 2/337 (0.6%) | 0/339 (0%) | ||
UPPER LIMB FRACTURE | 0/337 (0%) | 1/339 (0.3%) | ||
Investigations | ||||
BLOOD CREATINE PHOSPHOKINASE INCREASED | 1/337 (0.3%) | 0/339 (0%) | ||
BLOOD CREATININE INCREASED | 0/337 (0%) | 1/339 (0.3%) | ||
Metabolism and nutrition disorders | ||||
DEHYDRATION | 1/337 (0.3%) | 0/339 (0%) | ||
HYPERGLYCAEMIA | 1/337 (0.3%) | 1/339 (0.3%) | ||
Musculoskeletal and connective tissue disorders | ||||
ARTHRALGIA | 3/337 (0.9%) | 2/339 (0.6%) | ||
ARTHRITIS | 1/337 (0.3%) | 0/339 (0%) | ||
CERVICAL SPINAL STENOSIS | 0/337 (0%) | 1/339 (0.3%) | ||
INTERVERTEBRAL DISC PROTRUSION | 0/337 (0%) | 1/339 (0.3%) | ||
JOINT INSTABILITY | 1/337 (0.3%) | 0/339 (0%) | ||
MUSCULOSKELETAL CHEST PAIN | 0/337 (0%) | 1/339 (0.3%) | ||
OSTEOARTHRITIS | 2/337 (0.6%) | 1/339 (0.3%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
BENIGN PANCREATIC NEOPLASM | 0/337 (0%) | 1/339 (0.3%) | ||
BRAIN NEOPLASM BENIGN | 1/337 (0.3%) | 0/339 (0%) | ||
BREAST CANCER | 1/337 (0.3%) | 1/339 (0.3%) | ||
BREAST CANCER IN SITU | 0/337 (0%) | 1/339 (0.3%) | ||
CARCINOID TUMOUR PULMONARY | 0/337 (0%) | 1/339 (0.3%) | ||
ENDOMETRIAL CANCER | 0/337 (0%) | 1/339 (0.3%) | ||
LARGE CELL CARCINOMA OF THE RESPIRATORY TRACT STAGE UNSPECIFIED | 0/337 (0%) | 1/339 (0.3%) | ||
METASTATIC NEOPLASM | 0/337 (0%) | 1/339 (0.3%) | ||
NEUROENDOCRINE CARCINOMA | 0/337 (0%) | 1/339 (0.3%) | ||
NON-SMALL CELL LUNG CANCER | 1/337 (0.3%) | 0/339 (0%) | ||
OESOPHAGEAL CARCINOMA | 0/337 (0%) | 1/339 (0.3%) | ||
OVARIAN CANCER STAGE III | 0/337 (0%) | 1/339 (0.3%) | ||
PROSTATE CANCER | 2/337 (0.6%) | 1/339 (0.3%) | ||
PROSTATE CANCER STAGE II | 0/337 (0%) | 1/339 (0.3%) | ||
SARCOMA | 0/337 (0%) | 1/339 (0.3%) | ||
Nervous system disorders | ||||
CEREBROVASCULAR ACCIDENT | 0/337 (0%) | 2/339 (0.6%) | ||
CERVICOBRACHIAL SYNDROME | 0/337 (0%) | 1/339 (0.3%) | ||
COMPLICATED MIGRAINE | 1/337 (0.3%) | 0/339 (0%) | ||
DIABETIC NEUROPATHY | 1/337 (0.3%) | 0/339 (0%) | ||
ISCHAEMIC STROKE | 0/337 (0%) | 1/339 (0.3%) | ||
METABOLIC ENCEPHALOPATHY | 1/337 (0.3%) | 0/339 (0%) | ||
PRESYNCOPE | 1/337 (0.3%) | 0/339 (0%) | ||
RUPTURED CEREBRAL ANEURYSM | 1/337 (0.3%) | 0/339 (0%) | ||
SYNCOPE | 1/337 (0.3%) | 3/339 (0.9%) | ||
TRANSIENT ISCHAEMIC ATTACK | 1/337 (0.3%) | 3/339 (0.9%) | ||
UNRESPONSIVE TO STIMULI | 0/337 (0%) | 1/339 (0.3%) | ||
Psychiatric disorders | ||||
GENERALISED ANXIETY DISORDER | 0/337 (0%) | 1/339 (0.3%) | ||
MAJOR DEPRESSION | 1/337 (0.3%) | 1/339 (0.3%) | ||
SUICIDAL IDEATION | 1/337 (0.3%) | 0/339 (0%) | ||
Renal and urinary disorders | ||||
NEPHROLITHIASIS | 0/337 (0%) | 1/339 (0.3%) | ||
NEPHROTIC SYNDROME | 0/337 (0%) | 1/339 (0.3%) | ||
RENAL FAILURE ACUTE | 3/337 (0.9%) | 0/339 (0%) | ||
Reproductive system and breast disorders | ||||
BENIGN PROSTATIC HYPERPLASIA | 0/337 (0%) | 1/339 (0.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
ACUTE RESPIRATORY FAILURE | 1/337 (0.3%) | 0/339 (0%) | ||
ASTHMA | 0/337 (0%) | 1/339 (0.3%) | ||
CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 2/337 (0.6%) | 1/339 (0.3%) | ||
HYPOXIA | 0/337 (0%) | 1/339 (0.3%) | ||
NASAL POLYPS | 0/337 (0%) | 1/339 (0.3%) | ||
PULMONARY EMBOLISM | 1/337 (0.3%) | 1/339 (0.3%) | ||
PULMONARY MASS | 1/337 (0.3%) | 1/339 (0.3%) | ||
RESPIRATORY FAILURE | 1/337 (0.3%) | 1/339 (0.3%) | ||
Skin and subcutaneous tissue disorders | ||||
ANGIOEDEMA | 0/337 (0%) | 1/339 (0.3%) | ||
Vascular disorders | ||||
ANEURYSM | 1/337 (0.3%) | 0/339 (0%) | ||
AORTIC ANEURYSM | 1/337 (0.3%) | 2/339 (0.6%) | ||
AORTIC STENOSIS | 1/337 (0.3%) | 1/339 (0.3%) | ||
FEMORAL ARTERY OCCLUSION | 1/337 (0.3%) | 0/339 (0%) | ||
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE | 0/337 (0%) | 2/339 (0.6%) | ||
PERIPHERAL VASCULAR DISORDER | 1/337 (0.3%) | 1/339 (0.3%) | ||
SUBCLAVIAN ARTERY ANEURYSM | 0/337 (0%) | 1/339 (0.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
ABT-335 + Atorvastatin | Placebo + Atorvastatin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 235/337 (69.7%) | 241/339 (71.1%) | ||
Gastrointestinal disorders | ||||
CONSTIPATION | 17/337 (5%) | 14/339 (4.1%) | ||
DIARRHOEA | 23/337 (6.8%) | 25/339 (7.4%) | ||
NAUSEA | 24/337 (7.1%) | 20/339 (5.9%) | ||
General disorders | ||||
FATIGUE | 23/337 (6.8%) | 17/339 (5%) | ||
OEDEMA PERIPHERAL | 15/337 (4.5%) | 19/339 (5.6%) | ||
Infections and infestations | ||||
BRONCHITIS | 24/337 (7.1%) | 30/339 (8.8%) | ||
NASOPHARYNGITIS | 44/337 (13.1%) | 38/339 (11.2%) | ||
SINUSITIS | 20/337 (5.9%) | 30/339 (8.8%) | ||
UPPER RESPIRATORY TRACT INFECTION | 53/337 (15.7%) | 58/339 (17.1%) | ||
URINARY TRACT INFECTION | 18/337 (5.3%) | 14/339 (4.1%) | ||
Investigations | ||||
BLOOD CREATININE INCREASED | 22/337 (6.5%) | 6/339 (1.8%) | ||
Metabolism and nutrition disorders | ||||
DIABETES MELLITUS | 27/337 (8%) | 11/339 (3.2%) | ||
Musculoskeletal and connective tissue disorders | ||||
ARTHRALGIA | 29/337 (8.6%) | 36/339 (10.6%) | ||
BACK PAIN | 36/337 (10.7%) | 43/339 (12.7%) | ||
MUSCLE SPASMS | 24/337 (7.1%) | 23/339 (6.8%) | ||
MUSCULOSKELETAL PAIN | 22/337 (6.5%) | 15/339 (4.4%) | ||
MYALGIA | 26/337 (7.7%) | 32/339 (9.4%) | ||
PAIN IN EXTREMITY | 44/337 (13.1%) | 26/339 (7.7%) | ||
Nervous system disorders | ||||
DIZZINESS | 29/337 (8.6%) | 20/339 (5.9%) | ||
HEADACHE | 38/337 (11.3%) | 43/339 (12.7%) | ||
Psychiatric disorders | ||||
INSOMNIA | 18/337 (5.3%) | 20/339 (5.9%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
COUGH | 23/337 (6.8%) | 18/339 (5.3%) | ||
Vascular disorders | ||||
HYPERTENSION | 17/337 (5%) | 36/339 (10.6%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
Name/Title | Global Medical Services |
---|---|
Organization | AbbVie (prior sponsor, Abbott) |
Phone | 800-633-9110 |
- M10-158