Evaluate Safety and Efficacy of ABT-335 in Combination With Simvastatin in Subjects With Multiple Abnormal Lipid Levels in the Blood

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00300456
• Collaborator: (none)
• Enrollment: 657
• Location: 1
• Arms: 6

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of fenofibric acid (ABT-335)

• simvastatin combination therapy with ABT-335 and simvastatin monotherapy in subjects with multiple abnormal lipid levels in the blood.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia; Coronary Heart Disease; Mixed Dyslipidemia	Drug: ABT-335; Drug: Simvastatin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 657 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Prospective Study Comparing the Safety and Efficacy of ABT-335 and Simvastatin Combination Therapy to ABT-335 and Simvastatin Monotherapy in Subjects With Mixed Dyslipidemia
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A ABT-335 + 20 mg simvastatin	Drug: ABT-335; 135 mg, daily, 12 weeks; Drug: Simvastatin; daily, 12 weeks, see Arm Description for dosage information
Active Comparator: B ABT-335 + 40 mg simvastatin	Drug: ABT-335; 135 mg, daily, 12 weeks; Drug: Simvastatin; daily, 12 weeks, see Arm Description for dosage information
Placebo Comparator: C ABT-335 monotherapy	Drug: ABT-335; 135 mg, daily, 12 weeks; Drug: Placebo; Daily, 12 weeks, see Arm Description for placebo information
Placebo Comparator: D 20 mg simvastatin monotherapy	Drug: Simvastatin; daily, 12 weeks, see Arm Description for dosage information; Drug: Placebo; Daily, 12 weeks, see Arm Description for placebo information
Placebo Comparator: E 40 mg simvastatin monotherapy	Drug: Simvastatin; daily, 12 weeks, see Arm Description for dosage information; Drug: Placebo; Daily, 12 weeks, see Arm Description for placebo information
Placebo Comparator: F 80 mg simvastatin monotherapy	Drug: Simvastatin; daily, 12 weeks, see Arm Description for dosage information; Drug: Placebo; Daily, 12 weeks, see Arm Description for placebo information

Outcome Measures

Primary Outcome Measures

1. Mean 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

3. Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit [Baseline to 12 Weeks (Final Visit)]

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

Secondary Outcome Measures

1. 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

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 Total Cholesterol From Baseline to Final Visit [Baseline to 12 Weeks (Final Visit)]

   [(Week 12 total cholesterol minus baseline total cholesterol)/baseline total cholesterol] x 100

4. Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit [Baseline to 12 Weeks (Final Visit)]

   [(Week 12 Apo B minus baseline Apo B)/baseline Apo B] x 100

5. 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

• Subjects agree to utilize adequate birth control methods and to adhere to the American Heart Association (AHA) diet.

Exclusion Criteria:

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

• Patients who are taking certain medications or unstable dose of specific 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	Global Medical Information	North Chicago	Illinois	United States	60064

Sponsors and Collaborators

• Abbott

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00300456
• Other Study ID Numbers: M05-749
• First Posted: Mar 9, 2006
• Last Update Posted: Jun 3, 2009
• Last Verified: May 1, 2009

• Keywords provided by , ,: Dyslipidemia; Coronary Heart Disease; Mixed Dyslipidemia
• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Dyslipidemias; Simvastatin

Study Results

Participant Flow

Pre-assignment Detail	Seven subjects were randomized but never treated: 2 were taking a prohibited concomitant medication, 1 did not meet the entry criteria for lipid levels, 1 had an abnormal baseline electrocardiogram, 1 was unable to swallow pills, and 2 withdrew consent.

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Period Title: Overall Study
STARTED	119	118	119	119	116	59
COMPLETED	103	102	98	105	99	48
NOT COMPLETED	16	16	21	14	17	11

Baseline Characteristics

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin	Total
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily	Total of all reporting groups
Overall Participants	119	118	119	119	116	59	650
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	101 84.9%	96 81.4%	98 82.4%	104 87.4%	104 89.7%	48 81.4%	551 84.8%
>=65 years	18 15.1%	22 18.6%	21 17.6%	15 12.6%	12 10.3%	11 18.6%	99 15.2%
Sex: Female, Male (Count of Participants)
Female	59 49.6%	57 48.3%	68 57.1%	56 47.1%	61 52.6%	31 52.5%	332 51.1%
Male	60 50.4%	61 51.7%	51 42.9%	63 52.9%	55 47.4%	28 47.5%	318 48.9%
Region of Enrollment (participants) [Number]
North America	119 100%	118 100%	119 100%	119 100%	116 100%	59 100%	650 100%

Outcome Measures

1. Primary Outcome

Title	Mean 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 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	113	111	113	116	112	56
Mean (Standard Error) [percent change]	-37.4 (2.75)	-42.7 (2.77)	-31.7 (2.74)	-14.2 (2.71)	-22.4 (2.76)	-20.2 (3.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 20 mg Simvastatin, 20 mg Simvastatin
	Comments	An n = 92 per arm would provide >99% power to detect a 24% decrease in triglycerides relative to statin monotherapy for each combo therapy dose, assuming an SD of 30%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Simvastatin, 40 mg Simvastatin
	Comments	An n = 92 per arm would provide >99% power to detect 24% decrease in triglycerides relative to statin monotherapy for each combo therapy dose, assuming an SD of 30%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

2. 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 HDL-C value and at least 1 postbaseline HDL-C value, last observation carried forward

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	105	106	107	114	102	52
Mean (Standard Error) [percent change]	17.8 (1.86)	18.9 (1.86)	16.2 (1.85)	7.2 (1.80)	8.5 (1.89)	6.8 (2.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 20 mg Simvastatin, 20 mg Simvastatin
	Comments	An n = 92 per arm would provide 98% power to detect a 9% increase in HDL-C relative to statin monotherapy for each combo therapy dose, assuming an SD of 15%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Simvastatin, 40 mg Simvastatin
	Comments	An n = 92 per arm would provide 98% power to detect a 9% increase in HDL-C relative to statin monotherapy for each combo therapy dose, assuming an SD of 15%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

3. Primary Outcome

Title	Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit
Description	[(Week 12 LDL-C minus baseline LDL-C)/baseline LDL-C] x 100
Time Frame	Baseline to 12 Weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	109	108	107	116	106	55
Mean (Standard Error) [percent change]	-24.0 (1.94)	-25.3 (1.96)	-4.0 (1.96)	-22.4 (1.90)	-31.7 (1.98)	-40.8 (2.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 20 mg Simvastatin, ABT-335
	Comments	An n = 92 per arm would provide >99% power to detect an 11% decrease in LDL-C relative to ABT-335 monotherapy for each combo therapy dose, assuming an SD of 15%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABT-335 + 40 mg Simvastatin, ABT-335
	Comments	An n = 92 per arm would provide >99% power to detect an 11% decrease in LDL-C relative to ABT-335 monotherapy for each combo therapy dose, assuming an SD of 15%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	alpha = 0.05, all 3 primary endpoints had to show superiority of combo therapy in order to declare combo therapy successful at a given statin dose, Hochberg method for multiple comparison adjustment for 2 statin doses
	Method	ANCOVA
	Comments

4. 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, LOCF

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	104	104	107	114	103	52
Mean (Standard Error) [percent change]	-30.7 (1.48)	-35.0 (1.48)	-17.3 (1.46)	-24.4 (1.43)	-35.9 (1.49)	-40.6 (2.06)

5. 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, LOCF

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	109	111	110	112	110	54
Mean (Standard Error) [percent change]	-38.9 (4.06)	-51.1 (4.03)	-36.9 (4.04)	-19.2 (4.04)	-35.7 (4.06)	-30.0 (5.66)

6. Secondary Outcome

Title	Mean Percent Change in Total Cholesterol From Baseline to Final Visit
Description	[(Week 12 total cholesterol minus baseline total cholesterol)/baseline total cholesterol] x 100
Time Frame	Baseline to 12 Weeks (Final Visit)

Outcome Measure Data

Analysis Population Description

All randomized subjects with a baseline total cholesterol value and at least 1 postbaseline total cholesterol value, LOCF

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	112	111	113	116	112	56
Mean (Standard Error) [percent change]	-23.9 (1.20)	-27.1 (1.21)	-12.4 (1.20)	-19.8 (1.19)	-30.0 (1.21)	-33.6 (1.67)

7. Secondary Outcome

Title	Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit
Description	[(Week 12 Apo B minus baseline Apo B)/baseline Apo B] 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, LOCF

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	109	110	112	113	112	54
Mean (Standard Error) [percent change]	-29.5 (1.47)	-31.2 (1.47)	-17.6 (1.45)	-22.9 (1.45)	-32.7 (1.46)	-38.9 (2.05)

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, LOCF

Arm/Group Title	ABT-335 + 20 mg Simvastatin	ABT-335 + 40 mg Simvastatin	ABT-335	20 mg Simvastatin	40 mg Simvastatin	80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily	ABT-335 + 40 mg simvastatin combination therapy once daily	ABT-335 monotherapy once daily	20 mg simvastatin monotherapy once daily	40 mg simvastatin monotherapy once daily	80 mg simvastatin monotherapy once daily
Measure Participants	111	110	112	113	112	54
Median (Inter-Quartile Range) [percent change]	-26.8 (48.27)	-32.1 (48.70)	-15.8 (48.01)	-11.4 (48.18)	-14.8 (48.25)	-19.8 (67.84)

Adverse Events

Arm/Group Title	ABT-335 + 20 mg Simvastatin		ABT-335 + 40 mg Simvastatin		ABT-335		20 mg Simvastatin		40 mg Simvastatin		80 mg Simvastatin
Arm/Group Description	ABT-335 + 20 mg simvastatin combination therapy once daily		ABT-335 + 40 mg simvastatin combination therapy once daily		ABT-335 monotherapy once daily		20 mg simvastatin monotherapy once daily		40 mg simvastatin monotherapy once daily		80 mg simvastatin monotherapy once daily
All Cause Mortality
	ABT-335 + 20 mg Simvastatin		ABT-335 + 40 mg Simvastatin		ABT-335		20 mg Simvastatin		40 mg Simvastatin		80 mg Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ABT-335 + 20 mg Simvastatin		ABT-335 + 40 mg Simvastatin		ABT-335		20 mg Simvastatin		40 mg Simvastatin		80 mg Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		3/ (NaN)		6/ (NaN)		1/ (NaN)		1/ (NaN)		2/ (NaN)
Cardiac disorders
Angina pectoris	1/119 (0.8%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Angina unstable	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Mitral valve incompetence	0/119 (0%)		1/118 (0.8%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Myocardial infarction	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Gastrointestinal disorders
Colonic polyp	0/119 (0%)		0/118 (0%)		0/119 (0%)		1/119 (0.8%)		0/116 (0%)		0/59 (0%)
General disorders
Chest pain	0/119 (0%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		1/59 (1.7%)
Injury, poisoning and procedural complications
Fall	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Gun shot wound	0/119 (0%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		1/59 (1.7%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Nervous system disorders
Cerebrovascular accident	0/119 (0%)		1/118 (0.8%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Psychiatric disorders
Major depression	0/119 (0%)		1/118 (0.8%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Renal and urinary disorders
Bladder prolapse	0/119 (0%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		1/116 (0.9%)		0/59 (0%)
Reproductive system and breast disorders
Pelvic prolapse	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Uterine prolapse	0/119 (0%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		1/116 (0.9%)		0/59 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Vascular disorders
Arterial hemorrhage	0/119 (0%)		0/118 (0%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	ABT-335 + 20 mg Simvastatin		ABT-335 + 40 mg Simvastatin		ABT-335		20 mg Simvastatin		40 mg Simvastatin		80 mg Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/ (NaN)		72/ (NaN)		67/ (NaN)		60/ (NaN)		65/ (NaN)		26/ (NaN)
Gastrointestinal disorders
Abdominal pain	1/119 (0.8%)		4/118 (3.4%)		3/119 (2.5%)		1/119 (0.8%)		1/116 (0.9%)		0/59 (0%)
Abdominal pain upper	4/119 (3.4%)		2/118 (1.7%)		3/119 (2.5%)		1/119 (0.8%)		2/116 (1.7%)		2/59 (3.4%)
Constipation	2/119 (1.7%)		4/118 (3.4%)		6/119 (5%)		3/119 (2.5%)		3/116 (2.6%)		1/59 (1.7%)
Diarrhea	2/119 (1.7%)		5/118 (4.2%)		5/119 (4.2%)		5/119 (4.2%)		9/116 (7.8%)		4/59 (6.8%)
Nausea	3/119 (2.5%)		5/118 (4.2%)		5/119 (4.2%)		4/119 (3.4%)		5/116 (4.3%)		1/59 (1.7%)
Vomiting	0/119 (0%)		2/118 (1.7%)		2/119 (1.7%)		1/119 (0.8%)		1/116 (0.9%)		2/59 (3.4%)
General disorders
Dyspepsia	5/119 (4.2%)		7/118 (5.9%)		8/119 (6.7%)		3/119 (2.5%)		6/116 (5.2%)		1/59 (1.7%)
Fatigue	0/119 (0%)		2/118 (1.7%)		4/119 (3.4%)		3/119 (2.5%)		0/116 (0%)		1/59 (1.7%)
Pain	5/119 (4.2%)		1/118 (0.8%)		6/119 (5%)		1/119 (0.8%)		4/116 (3.4%)		0/59 (0%)
Infections and infestations
Influenza	3/119 (2.5%)		3/118 (2.5%)		0/119 (0%)		2/119 (1.7%)		4/116 (3.4%)		2/59 (3.4%)
Nasopharyngitis	9/119 (7.6%)		9/118 (7.6%)		7/119 (5.9%)		11/119 (9.2%)		4/116 (3.4%)		1/59 (1.7%)
Sinusitis	3/119 (2.5%)		6/118 (5.1%)		3/119 (2.5%)		0/119 (0%)		3/116 (2.6%)		0/59 (0%)
Upper respiratory tract infection	2/119 (1.7%)		8/118 (6.8%)		7/119 (5.9%)		6/119 (5%)		11/116 (9.5%)		3/59 (5.1%)
Injury, poisoning and procedural complications
Joint sprain	0/119 (0%)		0/118 (0%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		2/59 (3.4%)
Investigations
Alanine aminotransferase increased	5/119 (4.2%)		2/118 (1.7%)		1/119 (0.8%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Aspartate aminotransferase increased	4/119 (3.4%)		2/118 (1.7%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Blood creatine phosphokinase increased	4/119 (3.4%)		1/118 (0.8%)		0/119 (0%)		1/119 (0.8%)		3/116 (2.6%)		2/59 (3.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/119 (5.9%)		7/118 (5.9%)		3/119 (2.5%)		8/119 (6.7%)		6/116 (5.2%)		2/59 (3.4%)
Back pain	10/119 (8.4%)		4/118 (3.4%)		9/119 (7.6%)		8/119 (6.7%)		9/116 (7.8%)		2/59 (3.4%)
Muscle spasms	1/119 (0.8%)		5/118 (4.2%)		2/119 (1.7%)		3/119 (2.5%)		8/116 (6.9%)		1/59 (1.7%)
Musculoskeletal pain	3/119 (2.5%)		2/118 (1.7%)		0/119 (0%)		2/119 (1.7%)		4/116 (3.4%)		0/59 (0%)
Myalgia	5/119 (4.2%)		3/118 (2.5%)		6/119 (5%)		4/119 (3.4%)		6/116 (5.2%)		3/59 (5.1%)
Neck pain	2/119 (1.7%)		1/118 (0.8%)		1/119 (0.8%)		0/119 (0%)		5/116 (4.3%)		0/59 (0%)
Pain in extremity	6/119 (5%)		3/118 (2.5%)		6/119 (5%)		6/119 (5%)		6/116 (5.2%)		1/59 (1.7%)
Nervous system disorders
Dizziness	4/119 (3.4%)		0/118 (0%)		5/119 (4.2%)		3/119 (2.5%)		1/116 (0.9%)		2/59 (3.4%)
Headache	11/119 (9.2%)		25/118 (21.2%)		18/119 (15.1%)		14/119 (11.8%)		24/116 (20.7%)		5/59 (8.5%)
Hypoesthesia	0/119 (0%)		0/118 (0%)		3/119 (2.5%)		1/119 (0.8%)		2/116 (1.7%)		2/59 (3.4%)
Sinus headache	2/119 (1.7%)		2/118 (1.7%)		5/119 (4.2%)		1/119 (0.8%)		4/116 (3.4%)		0/59 (0%)
Renal and urinary disorders
Pollakiuria	0/119 (0%)		4/118 (3.4%)		0/119 (0%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	4/119 (3.4%)		7/118 (5.9%)		3/119 (2.5%)		5/119 (4.2%)		5/116 (4.3%)		3/59 (5.1%)
Epistaxis	4/119 (3.4%)		0/118 (0%)		2/119 (1.7%)		0/119 (0%)		0/116 (0%)		0/59 (0%)
Nasal congestion	5/119 (4.2%)		2/118 (1.7%)		4/119 (3.4%)		1/119 (0.8%)		0/116 (0%)		0/59 (0%)
Pharyngolaryngeal pain	4/119 (3.4%)		3/118 (2.5%)		3/119 (2.5%)		1/119 (0.8%)		2/116 (1.7%)		0/59 (0%)
Sinus congestion	3/119 (2.5%)		1/118 (0.8%)		2/119 (1.7%)		2/119 (1.7%)		4/116 (3.4%)		1/59 (1.7%)
Vascular disorders
Hypertension	0/119 (0%)		3/118 (2.5%)		0/119 (0%)		0/119 (0%)		2/116 (1.7%)		2/59 (3.4%)

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.