Study to Evaluate the Long-Term Safety and Efficacy of ABT-335, in Combination With Three Different Statins in Subjects With Mixed Dyslipidemia.

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00300430
• Collaborator: (none)
• Enrollment: 1,911
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

The primary purpose of this study is to test the safety and the effects of using an investigational drug regimen; once daily ABT-335 (Investigational drug) administered in combination with once daily atorvastatin calcium, rosuvastatin calcium or simvastatin in patients with abnormal lipid levels in the blood.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia; Coronary Heart Disease; Mixed Dyslipidemia	Drug: ABT-335 and rosuvastatin calcium; Drug: ABT-335 and atorvastatin calcium; Drug: ABT-335 and simvastatin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1911 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term, Open-Label, Safety Extension Study of the Combination of Fenofibric Acid and Statin Therapy for Subjects With Mixed Dyslipidemia
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A 20 mg drug and ABT-335	Drug: ABT-335 and rosuvastatin calcium; ABT-335 135 mg plus rosuvastatin calcium daily, 52 weeks; Other Names: ABT-335 TRILIPIX
Active Comparator: B 40 mg drug and ABT 335	Drug: ABT-335 and atorvastatin calcium; ABT-335 135 mg plus atorvastatin calcium daily, 52 weeks; Other Names: ABT-335 TRILIPIX
Active Comparator: C 40 mg drug and ABT-335	Drug: ABT-335 and simvastatin; ABT-335 135 mg plus simvastatin daily, 52 weeks; Other Names: ABT-335 TRILIPIX

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study [Anytime after initiation of combination therapy (either in the double-blind or open-label study) to within 30 days after the last dose of combination therapy]

Secondary Outcome Measures

1. Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

2. Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

3. Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

4. Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study [Baseline to Week 52 in this open-label study]

5. Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

6. Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

7. Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

8. Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study [Baseline to Week 52 of the open-label study]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult male and female subjects who voluntarily sign the informed consent.

• Subject has successfully completed one of the three ABT-335, rosuvastatin, simvastatin and atorvastatin combination therapy studies.

Exclusion Criteria:

• Subject is using or will use investigational medications, except as approved by Abbott.

• Subject has prematurely discontinued his/her initial therapy one of the prior ABT-335, rosuvastatin, simvastatin and atorvastatin calcium combination therapy studies.

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: NCT00300430
• Other Study ID Numbers: M05-758
• First Posted: Mar 9, 2006
• Last Update Posted: Jul 23, 2009
• Last Verified: Jun 1, 2009

• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Dyslipidemias; Calcium, Dietary; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Fenofibrate; Calcium

Study Results

Participant Flow

Pre-assignment Detail	1895 subjects were treated in this study. 306 others who did not enroll in this study but were treated with combo therapy in preceding double-blind studies are included in analyses of adverse events. Six subjects were enrolled, but never received study drug. An additional 10 subjects from a site that was closed were not included in any analysis.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Period Title: Overall Study
STARTED	1186	514	501
COMPLETED	819	345	350
NOT COMPLETED	367	169	151

Baseline Characteristics

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin	Total
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy	Total of all reporting groups
Overall Participants	1186	514	501	2201
Age (Count of Participants)
<=18 years	0 0%	0 0%	1 0.2%	1 0%
Between 18 and 65 years	965 81.4%	440 85.6%	397 79.2%	1802 81.9%
>=65 years	221 18.6%	74 14.4%	103 20.6%	398 18.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (10.79)	54.1 (10.25)	55.5 (10.86)	55.0 (10.69)
Sex: Female, Male (Count of Participants)
Female	608 51.3%	256 49.8%	256 51.1%	1120 50.9%
Male	578 48.7%	258 50.2%	245 48.9%	1081 49.1%
Region of Enrollment (participants) [Number]
North America	1186 100%	514 100%	501 100%	2201 100%

Outcome Measures

1. Secondary Outcome

Title	Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	284	120	122
Median (Full Range) [percent change]	-53.0 (27.67)	-47.7 (24.62)	-56.2 (24.56)

2. Secondary Outcome

Title	Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	284	120	121
Mean (Standard Deviation) [percent change]	25.2 (23.22)	25.1 (25.08)	19.4 (20.58)

3. Secondary Outcome

Title	Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	283	120	121
Mean (Standard Deviation) [percent change]	-41.6 (20.77)	-30.2 (21.83)	-38.1 (19.09)

4. Secondary Outcome

Title	Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study
Time Frame	Baseline to Week 52 in this open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	284	120	121
Mean (Standard Deviation) [percent change]	-48.8 (15.80)	-36.6 (16.90)	-44.3 (15.72)

5. Secondary Outcome

Title	Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	272	117	122
Mean (Standard Deviation) [percent change]	-56.9 (27.85)	-37.7 (63.12)	-52.2 (36.54)

6. Secondary Outcome

Title	Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	284	120	122
Mean (Standard Deviation) [percent change]	-37.9 (13.14)	-27.5 (14.60)	-35.0 (13.01)

7. Secondary Outcome

Title	Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	277	115	120
Mean (Standard Deviation) [percent change]	-44.8 (15.40)	-35.5 (14.85)	-42.9 (14.23)

8. Primary Outcome

Title	Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study
Time Frame	Anytime after initiation of combination therapy (either in the double-blind or open-label study) to within 30 days after the last dose of combination therapy

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or in this open-label study. All adverse events in the preceding studies or in this study occurring with exposure to combination therapy are summarized.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	1186	514	501
Number [percentage of participants]	83 7%	86 16.7%	85 17%

9. Secondary Outcome

Title	Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study
Time Frame	Baseline to Week 52 of the open-label study

Outcome Measure Data

Analysis Population Description

Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy	ABT-335 and 40 mg simvastatin combination therapy	ABT-335 and 40 mg atorvastatin combination therapy
Measure Participants	279	117	120
Median (Full Range) [percent change]	-38.87 (265.37)	-27.72 (93.62)	-39.13 (70.99)

Adverse Events

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin		ABT-335 + 40 mg Simvastatin		ABT-335 + 40 mg Atorvastatin
Arm/Group Description	ABT-335 and 20 mg rosuvastatin combination therapy		ABT-335 and 40 mg simvastatin combination therapy		ABT-335 and 40 mg atorvastatin combination therapy
All Cause Mortality
	ABT-335 + 20 mg Rosuvastatin		ABT-335 + 40 mg Simvastatin		ABT-335 + 40 mg Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ABT-335 + 20 mg Rosuvastatin		ABT-335 + 40 mg Simvastatin		ABT-335 + 40 mg Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/ (NaN)		40/ (NaN)		23/ (NaN)
Blood and lymphatic system disorders
Anemia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Cardiac disorders
Acute coronary syndrome	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Acute myocardial infarction	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Angina pectoris	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Angina unstable	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Atrial fibrillation	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Atrial flutter	2/1186 (0.2%)		1/514 (0.2%)		0/501 (0%)
Cardiac arrest	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Cardiac failure congestive	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Cardio-respiratory arrest	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Coronary artery disease	5/1186 (0.4%)		0/514 (0%)		0/501 (0%)
Mitral valve incompetence	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Myocardial infarction	4/1186 (0.3%)		1/514 (0.2%)		0/501 (0%)
Myocardial ischemia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Pericarditis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Sick sinus syndrome	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Ventricular tachycardia	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Congenital, familial and genetic disorders
Arnold-Chiari malformation	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Endocrine disorders
Hyperparathyroidism primary	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Eye disorders
Retinal detachment	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Vitreous detachment	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Gastrointestinal disorders
Abdominal hernia	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Abdominal pain upper	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Duodenitis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Dysphagia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Enterocele	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Gastroesophageal reflux disease	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Lower gastrointestinal hemorrhage	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Nausea	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Pancreatitis	1/1186 (0.1%)		0/514 (0%)		1/501 (0.2%)
Pancreatitis acute	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Small intestinal obstruction	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Umbilical hernia	0/1186 (0%)		2/514 (0.4%)		0/501 (0%)
Vomiting	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
General disorders
Chest discomfort	1/1186 (0.1%)		0/514 (0%)		2/501 (0.4%)
Chest pain	2/1186 (0.2%)		1/514 (0.2%)		2/501 (0.4%)
Non-cardiac chest pain	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Cholecystitis	2/1186 (0.2%)		0/514 (0%)		1/501 (0.2%)
Cholecystitis acute	2/1186 (0.2%)		0/514 (0%)		0/501 (0%)
Cholecystitis chronic	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Cholelithiasis	0/1186 (0%)		1/514 (0.2%)		1/501 (0.2%)
Immune system disorders
Latex allergy	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Infections and infestations
Abdominal wall infection	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Appendicitis	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Bacteremia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Cellulitis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Diverticulitis	4/1186 (0.3%)		0/514 (0%)		0/501 (0%)
Gastroenteritis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Gastroenteritis viral	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Hepatitis viral	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Orchitis	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Pneumonia	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Pneumonia pneumococcal	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Postoperative wound infection	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Subcutaneous abscess	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Upper respiratory tract infection	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Urinary tract infection	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/1186 (0.1%)		0/514 (0%)		1/501 (0.2%)
Device failure	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Hip fracture	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Humerus fracture	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Incisional hernia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Limb injury	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Post procedural hematoma	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Post procedural sepsis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Postoperative fever	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Skin laceration	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Investigations
Blood pressure increased	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Ultrasound kidney abnormal	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Metabolism and nutrition disorders
Obesity	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Cervical spinal stenosis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Intervertebral disc degeneration	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Intervertebral disc protrusion	3/1186 (0.3%)		1/514 (0.2%)		0/501 (0%)
Musculoskeletal chest pain	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Neck pain	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Osteoarthritis	6/1186 (0.5%)		4/514 (0.8%)		0/501 (0%)
Osteonecrosis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Rheumatoid arthritis	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Spinal osteoarthritis	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Carcinoid tumor	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Colon cancer	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Glioblastoma	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Lip and/or oral cavity cancer	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Lung neoplasm	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Ovarian adenoma	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Pituitary tumor benign	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Prostate cancer	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Uterine leiomyoma	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Nervous system disorders
Brain edema	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Brain stem infarction	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Carotid artery stenosis	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Cerebrovascular accident	0/1186 (0%)		1/514 (0.2%)		1/501 (0.2%)
Dementia	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Dizziness	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Dysarthria	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Grand mal convulsion	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Headache	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Hydrocephalus	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Lethargy	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Migraine	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Normal pressure hydrocephalus	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Presyncope	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Somnolence	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Syncope	2/1186 (0.2%)		1/514 (0.2%)		1/501 (0.2%)
Transient ischemic attack	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Trigeminal neuralgia	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Unresponsive to stimuli	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/1186 (0.1%)		1/514 (0.2%)		1/501 (0.2%)
Psychiatric disorders
Anxiety disorder	1/1186 (0.1%)		1/514 (0.2%)		0/501 (0%)
Confusional state	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Major depression	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Mental status changes	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Renal and urinary disorders
Calculus ureteric	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Glomerulonephritis proliferative	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Hematuria	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Nephrolithiasis	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Renal colic	1/1186 (0.1%)		0/514 (0%)		1/501 (0.2%)
Renal failure acute	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Renal impairment	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Reproductive system and breast disorders
Cystocele	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Menorrhagia	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Menstruation irregular	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Ovarian cyst	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Rectocele	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Uterine pain	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Uterine prolapse	2/1186 (0.2%)		0/514 (0%)		1/501 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Dyspnea	2/1186 (0.2%)		0/514 (0%)		0/501 (0%)
Pleural effusion	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Pulmonary embolism	2/1186 (0.2%)		0/514 (0%)		1/501 (0.2%)
Respiratory arrest	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Respiratory failure	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Vascular disorders
Aortic aneurysm	0/1186 (0%)		1/514 (0.2%)		0/501 (0%)
Deep vein thrombosis	4/1186 (0.3%)		1/514 (0.2%)		1/501 (0.2%)
Femoral arterial stenosis	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Hypotension	1/1186 (0.1%)		0/514 (0%)		1/501 (0.2%)
Intermittent claudication	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Thrombophlebitis superficial	1/1186 (0.1%)		0/514 (0%)		0/501 (0%)
Thrombosis	0/1186 (0%)		0/514 (0%)		1/501 (0.2%)
Other (Not Including Serious) Adverse Events
	ABT-335 + 20 mg Rosuvastatin		ABT-335 + 40 mg Simvastatin		ABT-335 + 40 mg Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	646/ (NaN)		308/ (NaN)		283/ (NaN)
Gastrointestinal disorders
Diarrhea	49/1186 (4.1%)		26/514 (5.1%)		33/501 (6.6%)
Dyspepsia	42/1186 (3.5%)		31/514 (6%)		28/501 (5.6%)
Nausea	61/1186 (5.1%)		23/514 (4.5%)		34/501 (6.8%)
Infections and infestations
Bronchitis	60/1186 (5.1%)		25/514 (4.9%)		23/501 (4.6%)
Nasopharyngitis	116/1186 (9.8%)		70/514 (13.6%)		58/501 (11.6%)
Sinusitis	91/1186 (7.7%)		40/514 (7.8%)		37/501 (7.4%)
Upper respiratory tract infection	145/1186 (12.2%)		69/514 (13.4%)		57/501 (11.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	86/1186 (7.3%)		54/514 (10.5%)		38/501 (7.6%)
Back pain	118/1186 (9.9%)		56/514 (10.9%)		42/501 (8.4%)
Muscle spasms	55/1186 (4.6%)		34/514 (6.6%)		35/501 (7%)
Myalgia	60/1186 (5.1%)		27/514 (5.3%)		25/501 (5%)
Pain in extremity	53/1186 (4.5%)		32/514 (6.2%)		33/501 (6.6%)
Nervous system disorders
Headache	160/1186 (13.5%)		75/514 (14.6%)		74/501 (14.8%)
Respiratory, thoracic and mediastinal disorders
Cough	49/1186 (4.1%)		35/514 (6.8%)		32/501 (6.4%)
Pharyngolaryngeal pain	23/1186 (1.9%)		26/514 (5.1%)		21/501 (4.2%)

Limitations/Caveats

This was an open-label study designed to assess the longer-term safety of the combination therapies. Evaluation of efficacy outcomes was a secondary objective.

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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.