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

Sponsor
AbbVie (prior sponsor, Abbott) (Industry)
Overall Status
Completed
CT.gov ID
NCT00616772
Collaborator
(none)
682
124
2
55
5.5
0.1

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

Study Type:
Interventional
Actual Enrollment :
682 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects With Type IIb Dyslipidemia With Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial
Study Start Date :
Feb 1, 2008
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
Sep 1, 2012

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:
  • Choline fenofibrate
  • Fenofibric acid
  • 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

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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

    Ages Eligible for Study:
    45 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT00616772
    Other Study ID Numbers:
    • M10-158
    First Posted:
    Feb 15, 2008
    Last Update Posted:
    Jul 2, 2018
    Last Verified:
    Dec 1, 2013

    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

    1. Primary Outcome
    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
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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

    [Not Specified]

    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
    Email
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT00616772
    Other Study ID Numbers:
    • M10-158
    First Posted:
    Feb 15, 2008
    Last Update Posted:
    Jul 2, 2018
    Last Verified:
    Dec 1, 2013