Safety and Efficacy Study Comparing ABT-335 Coadministered With Atorvastatin and Ezetimibe to Atorvastatin Coadministered With Ezetimibe in Subjects With Multiple Abnormal Lipid (Fat) Levels in the Blood

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00639158
• Collaborator: (none)
• Enrollment: 543
• Locations: 119
• Arms: 2
• Patients Per Site: 4.6

Study Details

Study Description

Brief Summary

The primary purpose of this study is to compare the safety and efficacy of ABT-335 (investigational drug) coadministered with atorvastatin and ezetimibe to atorvastatin coadministered with ezetimibe in subjects with abnormal lipid (fat) levels in the blood.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemias; Coronary Heart Disease; Combined (Atherogenic) Dyslipidemia; Mixed Dyslipidemia	Drug: ABT-335; Drug: placebo; Drug: atorvastatin; Drug: ezetimibe	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 543 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Prospective Study Comparing the Safety and Efficacy of ABT-335 in Combination With Atorvastatin and Ezetimibe to Atorvastatin in Combination With Ezetimibe in Subjects With Combined (Atherogenic) Dyslipidemia
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ABT-335 + atorvastatin + ezetimibe	Drug: ABT-335; 135 mg capsule, daily, 12 weeks; Other Names: TriLipix Fenofibric acid Choline Fenofibrate ; Drug: atorvastatin; 40 mg, tablet, daily, 12 weeks; Other Names: Lipitor ; Drug: ezetimibe; 10 mg capsule, daily, 12 weeks; Other Names: Ezetrol Zetia Ezemibe
Placebo Comparator: Placebo + atorvastatin + ezetimibe	Drug: placebo; placebo capsule, daily, 12 weeks; Drug: atorvastatin; 40 mg, tablet, daily, 12 weeks; Other Names: Lipitor ; Drug: ezetimibe; 10 mg capsule, daily, 12 weeks; Other Names: Ezetrol Zetia Ezemibe

Outcome Measures

Primary Outcome Measures

1. Median Percent Change in Triglycerides From Baseline to Final Visit [Baseline to 12 Weeks (Final Visit)]

   [(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides] x 100

2. Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C] x 100

Secondary Outcome Measures

1. Mean Percent Change in Apolipoprotein AI (apoAI) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 apoAI minus baseline apoAI)/baseline apoAI] x 100

2. Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Final Visit [Baseline to 12 weeks (final visit)]

   [(Week 12 VLDL-C minus baseline VLDL-C)/baseline VLDL-C] x 100

3. Mean Percent Change in Apolipoprotein CIII (apoCIII) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 apoCIII minus baseline apoCIII)/baseline apoCIII] x 100

4. Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 non-HDL-C minus baseline non-HDL-C)/baseline non-HDL-C] x 100

5. Mean Percent Change in Apolipoprotein B (apoB) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 apoB minus baseline apoB)/baseline apoB] x 100

6. Median Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Final Visit [Baseline to 12 weeks (Final Visit)]

   [(Week 12 hsCRP minus baseline hsCRP)/baseline hSCRP] x 100

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with mixed dyslipidemia (trigylcerides, > or = to 150 mg/dL to < 400 mg/dL; HDL-C < 40 mg/dL for males, < 50 mg/dL for females; LDL-C, > or = to 130 mg/dL).

• Subjects must agree to use adequate birth control methods and to adhere to the American Heart Association (AHA) Diet.

Exclusion Criteria:

• Subjects with unstable or uncontrolled medical conditions considered inappropriate in a clinical trial.

• Subjects with an unstable dose of medications or receiving Coumadin, oral, intravenous or intramuscular cyclosporine, statins, or certain other medications.

• Women who are pregnant or plan on becoming pregnant, or women who are lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35209
2		Columbiana	Alabama	United States	35051
3		Hueytown	Alabama	United States	35023
4		Ozark	Alabama	United States	36360
5		Tuscaloosa	Alabama	United States	35406
6		Sierra Vista	Arizona	United States	85635
7		Hot Springs	Arkansas	United States	71913
8		Carmichael	California	United States	95608
9		Concord	California	United States	94520
10		Long Beach	California	United States	90806
11		Long Beach	California	United States	90822
12		Los Angeles	California	United States	90057
13		Norwalk	California	United States	90650
14		Roseville	California	United States	95661
15		Sacramento	California	United States	95825
16		Santa Ana	California	United States	92701
17		Tustin	California	United States	92780
18		West Hills	California	United States	91307
19		Colorado Springs	Colorado	United States	80904
20		Denver	Colorado	United States	80206
21		Clearwater	Florida	United States	33756
22		Delray Beach	Florida	United States	33484
23		Fort Myers	Florida	United States	33907
24		Holly Hill	Florida	United States	32117
25		Jacksonville	Florida	United States	32216
26		Jacksonville	Florida	United States	32259
27		Kissimmee	Florida	United States	34741
28		Longwood	Florida	United States	32750
29		Miami	Florida	United States	33173
30		New Port Richey	Florida	United States	34652
31		New Smyrna Beach	Florida	United States	32168
32		Ocala	Florida	United States	34471
33		Ormond Beach	Florida	United States	32174
34		Pembroke Pines	Florida	United States	33002
35		Sarasota	Florida	United States	34233
36		Tampa	Florida	United States	33607
37		Winter Haven	Florida	United States	33880
38		Atlanta	Georgia	United States	30342
39		Augusta	Georgia	United States	30904
40		Roswell	Georgia	United States	30076
41		Suwanee	Georgia	United States	30024
42		Woodstock	Georgia	United States	30189
43		Boise	Idaho	United States	83704
44		Chicago	Illinois	United States	60607
45		Chicago	Illinois	United States	60610
46		Peoria	Illinois	United States	61602
47		Evansville	Indiana	United States	47713
48		Evansville	Indiana	United States	47714
49		Indianapolis	Indiana	United States	46260
50		Iowa City	Iowa	United States	52242
51		Arkansas City	Kansas	United States	67005
52		Overland Park	Kansas	United States	66202
53		Wichita	Kansas	United States	67207
54		Louisville	Kentucky	United States	40213
55		Mt. Sterling	Kentucky	United States	40353
56		Slidell	Louisiana	United States	70458
57		Baltimore	Maryland	United States	21209
58		Oxon Hill	Maryland	United States	20745
59		Brockton	Massachusetts	United States	02301
60		Edina	Minnesota	United States	55435
61		Olive Branch	Mississippi	United States	38654
62		St Louis	Missouri	United States	63110
63		St Louis	Missouri	United States	63141
64		St. Louis	Missouri	United States	63141
65		St. Peters	Missouri	United States	63376
66		Billings	Montana	United States	59101
67		Las Vegas	Nevada	United States	89123
68		Berlin	New Jersey	United States	08009
69		Elizabeth	New Jersey	United States	07202
70		Hillsborough	New Jersey	United States	08844
71		Trenton	New Jersey	United States	08611
72		Johnson City	New York	United States	13790
73		Charlotte	North Carolina	United States	28209
74		Hickory	North Carolina	United States	28601
75		Morehead City	North Carolina	United States	28557
76		Raleigh	North Carolina	United States	27609
77		Salisbury	North Carolina	United States	28144
78		Statesville	North Carolina	United States	25677
79		Winston-Salem	North Carolina	United States	27103
80		Cincinnati	Ohio	United States	45219
81		Mason	Ohio	United States	45040
82		Mogadore	Ohio	United States	44260
83		Warren	Ohio	United States	44483
84		Tulsa	Oklahoma	United States	74136
85		Hillsboro	Oregon	United States	97123
86		Duncansville	Pennsylvania	United States	16635
87		Harleysville	Pennsylvania	United States	19438
88		Jersey Shore	Pennsylvania	United States	17740
89		Lansdale	Pennsylvania	United States	19446
90		Melrose Park	Pennsylvania	United States	19027
91		Newtown	Pennsylvania	United States	18940
92		Perkasie	Pennsylvania	United States	18944
93		Philadelphia	Pennsylvania	United States	19114
94		Philadelphia	Pennsylvania	United States	19152
95		Pittsburgh	Pennsylvania	United States	15216
96		Sellersville	Pennsylvania	United States	18960
97		Tipton	Pennsylvania	United States	16684
98		Warminster	Pennsylvania	United States	18974
99		Cumberland	Rhode Island	United States	02864
100		Anderson	South Carolina	United States	29621
101		Greenville	South Carolina	United States	29615
102		Greer	South Carolina	United States	29651
103		Simpsonville	South Carolina	United States	29681
104		Summerville	South Carolina	United States	29485
105		Nashville	Tennessee	United States	37205
106		Dallas	Texas	United States	75230
107		Fort Worth	Texas	United States	76104
108		Houston	Texas	United States	77030
109		San Antonio	Texas	United States	78229
110		Salt Lake City	Utah	United States	84102
111		Salt Lake City	Utah	United States	84103
112		Salt Lake City	Utah	United States	84107
113		West Jordan	Utah	United States	84088
114		Norfolk	Virginia	United States	23502
115		Richmond	Virginia	United States	23294
116		Roanoke	Virginia	United States	24014
117		Virginia Beach	Virginia	United States	23455
118		Spokane	Washington	United States	99216
119		Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• Abbott

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00639158
• Other Study ID Numbers: M10-275
• First Posted: Mar 20, 2008
• Last Update Posted: Jun 13, 2011
• Last Verified: Jun 1, 2011

• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Dyslipidemias; Choline; Atorvastatin; Ezetimibe; Fenofibric acid; Fenofibrate

Study Results

Participant Flow

Pre-assignment Detail	One subject was randomized to the atorvastatin and ezetimibe treatment group and never received study drug.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Period Title: Overall Study
STARTED	272	270
COMPLETED	246	240
NOT COMPLETED	26	30

Baseline Characteristics

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	272	270	542
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	227 83.5%	206 76.3%	433 79.9%
>=65 years	45 16.5%	64 23.7%	109 20.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (11.23)	56.4 (10.67)	55.4 (10.99)
Age (participants) [Mean (Standard Deviation) ]
United States	54.4 (11.23) 20%	56.4 (10.67) 20.9%	55.4 (10.99) 10.2%
Sex: Female, Male (Count of Participants)
Female	143 52.6%	155 57.4%	298 55%
Male	129 47.4%	115 42.6%	244 45%

Outcome Measures

1. Primary Outcome

Title	Median Percent Change in Triglycerides From Baseline to Final Visit
Description	[(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides] x 100
Time Frame	Baseline to 12 Weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline triglyceride value and at least 1 postbaseline triglyceride value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	262	262
Median (Inter-Quartile Range) [Percent change]	-57.3 (22.32)	-39.7 (29.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	A sample size of 212 per arm provided 90% power and > 99% power with a 2-sided alpha = 0.05 level to detect differences between treatment arms of 6% and 17% in the percent change in HDL-C and TG, respectively, assuming an SD of 19% and 30%, respectively. This sample size provided an overall power of approximately 90% for the 2 primary comparisons. If a loss to follow-up rate of 8% was assumed, the sample size needed to be increased to 230 per arm to maintain the above power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	The treatment group comparisons for both primary efficacy variables must have demonstrated superiority of ABT-335 + atorvastatin + ezetimibe to declare this arm successful. Thus, no adjustments were made for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Mean Percent Change in Apolipoprotein AI (apoAI) From Baseline to Final Visit
Description	[(Week 12 apoAI minus baseline apoAI)/baseline apoAI] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline apoAI value and at least 1 postbaseline apoAI value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	248	239
Mean (Standard Error) [Percent change]	1.8 (0.74)	-1.3 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments	Corresponding baseline lipid value as the covariate and with effect for treatment group.

3. Primary Outcome

Title	Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit
Description	[(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline high density lipoprotein cholesterol (HDL-C) value and at least 1 postbaseline HDL-C value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	262	262
Mean (Standard Error) [Percent change]	13.0 (0.95)	4.2 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	A sample size of 212 per arm provided 90% power and > 99% power with a 2-sided alpha = 0.05 level to detect differences between treatment arms of 6% and 17% in the percent change in HDL-C and TG, respectively, assuming an SD of 19% and 30%, respectively. This sample size provided an overall power of approximately 90% for the 2 primary comparisons. If a loss to follow-up rate of 8% was assumed, the sample size needed to be increased to 230 per arm to maintain the above power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	The treatment group comparisons for both primary efficacy variables must have demonstrated superiority of ABT-335 + atorvastatin + ezetimibe to declare this arm successful. Thus, no adjustments were made for multiple comparisons.
	Method	ANCOVA
	Comments	Corresponding baseline lipid value as the covariate and with effect for treatment group.

4. Secondary Outcome

Title	Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Final Visit
Description	[(Week 12 VLDL-C minus baseline VLDL-C)/baseline VLDL-C] x 100
Time Frame	Baseline to 12 weeks (final visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline VLDL-C value and at least 1 postbaseline VLDL-C value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	261	262
Mean (Standard Error) [Percent change]	-57.8 (1.87)	-41.1 (1.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments	Corresponding baseline lipid value as the covariate and with effect for treatment group.

5. Secondary Outcome

Title	Mean Percent Change in Apolipoprotein CIII (apoCIII) From Baseline to Final Visit
Description	[(Week 12 apoCIII minus baseline apoCIII)/baseline apoCIII] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline apoCIII value and at least 1 postbaseline apoCIII value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	249	242
Mean (Standard Error) [Percent change]	-42.5 (1.22)	-25.3 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments	Corresponding lipid value as the covariate and with effect for treatment group.

6. Secondary Outcome

Title	Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit
Description	[(Week 12 non-HDL-C minus baseline non-HDL-C)/baseline non-HDL-C] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline non-HDL-C value and at least 1 postbaseline non-HDL-C value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	262	262
Mean (Standard Error) [Percent change]	-55.6 (0.94)	-51.0 (0.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments	Corresponding baseline lipid value as the covariate and with effect for treatment group.

7. Secondary Outcome

Title	Mean Percent Change in Apolipoprotein B (apoB) From Baseline to Final Visit
Description	[(Week 12 apoB minus baseline apoB)/baseline apoB] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline apoB value and at least 1 postbaseline apoB value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	248	239
Mean (Standard Error) [Percent change]	-49.1 (0.91)	-44.7 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments	Corresponding baseline lipid value as the covariate and with effect for treatment group.

8. Secondary Outcome

Title	Median Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Final Visit
Description	[(Week 12 hsCRP minus baseline hsCRP)/baseline hSCRP] x 100
Time Frame	Baseline to 12 weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline hsCRP value and at least 1 postbaseline hsCRP value, last observation carried forward.

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe	Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
Measure Participants	261	262
Median (Inter-Quartile Range) [Percent change]	-52.1 (102.82)	-40.3 (516.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe, Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Comments	Secondary endpoints were tested in fixed sequence. If superiority of ABT-335 + atorvastatin + ezetimibe treatment was demonstrated for primary endpoints, secondary endpoints were tested in ranked order of apoA1, VLDL-C, apoC3, non-HDL-C, apoB, and hsCRP at alpha = 0.05 level until 1 secondary endpoint failed to reach statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Rank-sum test

Adverse Events

Arm/Group Title	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe		Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
Arm/Group Description
All Cause Mortality
	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe		Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe		Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/272 (1.1%)		5/270 (1.9%)
Gastrointestinal disorders
Abdominal Pain Upper	1/272 (0.4%)		0/270 (0%)
Dyspepsia	1/272 (0.4%)		0/270 (0%)
Esophageal Pain	1/272 (0.4%)		0/270 (0%)
General disorders
Chest Pain	1/272 (0.4%)		0/270 (0%)
Non-Cardiac Chest Pain	1/272 (0.4%)		0/270 (0%)
Infections and infestations
Subcutaneous Abscess	0/272 (0%)		1/270 (0.4%)
Wound Infection Staphylococcal	1/272 (0.4%)		0/270 (0%)
Metabolism and nutrition disorders
Dehydration	0/272 (0%)		1/270 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer	0/272 (0%)		1/270 (0.4%)
Breast Cancer	0/272 (0%)		1/270 (0.4%)
Nervous system disorders
Cerebrovascular Accident	0/272 (0%)		1/270 (0.4%)
Other (Not Including Serious) Adverse Events
	ABT-335 + 40 mg Atorvastatin + 10 mg Ezetimibe		Placebo + 40 mg Atorvastatin + 10 mg Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/272 (15.1%)		51/270 (18.9%)
Gastrointestinal disorders
Diarrhea	9/272 (3.3%)		6/270 (2.2%)
Nausea	4/272 (1.5%)		9/270 (3.3%)
General disorders
Fatigue	6/272 (2.2%)		10/270 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/272 (2.2%)		10/270 (3.7%)
Muscle Spasms	10/272 (3.7%)		9/270 (3.3%)
Myalgia	7/272 (2.6%)		10/270 (3.7%)
Nervous system disorders
Headache	6/272 (2.2%)		9/270 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Not to publish or present the results before the publication of the multi-center investigator paper, but in no event shall be so restricted after the expiration of twelve (12) months from completion of the studies at all sites. Any presentation or publication to be submitted to Sponsor (in Draft of the same) for Sponsor review and comment.