A Year 2, Safety Extension Study of the Combination of ABT-335 and Statin Therapy for Subjects With Mixed Dyslipidemia

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00491530
• Collaborator: (none)
• Enrollment: 310
• Location: 1
• Arms: 3
• Duration (Months): 17.1
• Patients Per Site Per Month: 18.2

Study Details

Study Description

Brief Summary

The objective of the study is to assess the continued safety of the daily coadministration of ABT-335 in combination with rosuvastatin calcium, simvastatin or atorvastatin calcium.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Year 2, Long-Term, Open-Label, Safety Extension Study of the Combination of ABT-335 and Statin Therapy for Subjects With Mixed Dyslipidemia
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-335 + rosuvastatin calcium	Drug: ABT-335; Oral coadministration of ABT-335 (135 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: fenofibric acid ; Drug: rosuvastatin calcium; Oral coadministration of rosuvastatin calcium (20 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: Crestor
Experimental: ABT-335 + simvastatin	Drug: ABT-335; Oral coadministration of ABT-335 (135 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: fenofibric acid ; Drug: simvastatin; Oral coadministration of simvastatin (40 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: Zocor
Experimental: ABT-335 + atorvastatin calcium	Drug: ABT-335; Oral coadministration of ABT-335 (135 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: fenofibric acid ; Drug: atorvastatin calcium; Oral coadministration of atorvastatin calcium (40 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study; Other Names: Lipitor

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study [Anytime after initiation of combination therapy (in the preceding 12-week double-blind studies or in the preceding open-label year 1 study) up to 116 weeks, to within 30 days after the last dose of combination therapy.]

   All serious and non-serious adverse events are reported from the time of combination study drug initiation until 30 days after discontinuation of study drug. Adverse events are unfavorable changes in health that occur in subjects during a clinical trial or within a specified period following a trial. Serious adverse events are those that result in death, require inpatient hospitalization or the prolongation of hospitalization, result in congenital anomaly/birth defect, or significant disability/incapacity or are life-threatening.

Secondary Outcome Measures

1. Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 triglycerides minus baseline triglycerides)/baseline triglycerides] X 100. Baseline is the last value prior to the first dose of combination therapy.

2. Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 HDL-C minus baseline HDL-C)/baseline HDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.

3. Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 LDL-C minus baseline LDL-C)/baseline LDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.

4. Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 Non-HDL-C minus baseline Non-HDL-C)/baseline Non-HDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.

5. Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 VLDL-C minus baseline VLDL-C)/baseline VLDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.

6. Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study [Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)]

   [(Week 104 Total-C minus baseline Total-C)/baseline Total-C] X 100. Baseline is the last value prior to the first dose of combination therapy.

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 the treatment phase of the preceding open-label year 1 study.

Exclusion Criteria:

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

• Subject has prematurely discontinued his/her combination therapy administered in the preceding open-label year 1 study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Information Specialist	Abbott Park	Illinois	United States	60064

Sponsors and Collaborators

• Abbott

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00491530
• Other Study ID Numbers: M06-884
• First Posted: Jun 26, 2007
• Last Update Posted: Jan 20, 2012
• Last Verified: Jan 1, 2012

• Additional relevant MeSH terms: Dyslipidemias; Calcium, Dietary; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Fenofibric acid; Calcium

Study Results

Participant Flow

Recruitment Details	Subjects who had completed ABT-335/statin therapy in the preceding open-label year 1 study at a subset of sites were eligible for recruitment in this open-label year 2 extension study. Subjects continued to receive the treatment they had received in the preceding open-label year 1 study.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Period Title: Overall Study
STARTED	174	50	86
COMPLETED	162	44	81
NOT COMPLETED	12	6	5

Baseline Characteristics

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin	Total
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Total of all reporting groups
Overall Participants	174	50	86	310
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	138 79.3%	40 80%	68 79.1%	246 79.4%
>=65 years	36 20.7%	10 20%	18 20.9%	64 20.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.1 (10.71)	55.3 (10.55)	55.4 (10.94)	55.8 (10.72)
Sex: Female, Male (Count of Participants)
Female	77 44.3%	29 58%	42 48.8%	148 47.7%
Male	97 55.7%	21 42%	44 51.2%	162 52.3%
Region of Enrollment (participants) [Number]
United States	174 100%	50 100%	86 100%	310 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study
Description	All serious and non-serious adverse events are reported from the time of combination study drug initiation until 30 days after discontinuation of study drug. Adverse events are unfavorable changes in health that occur in subjects during a clinical trial or within a specified period following a trial. Serious adverse events are those that result in death, require inpatient hospitalization or the prolongation of hospitalization, result in congenital anomaly/birth defect, or significant disability/incapacity or are life-threatening.
Time Frame	Anytime after initiation of combination therapy (in the preceding 12-week double-blind studies or in the preceding open-label year 1 study) up to 116 weeks, 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 preceding open-label year 1 study, and in this open-label year 2 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	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	174	50	86
Number [percentage of participants]	94.8 54.5%	90.0 180%	97.7 113.6%

2. Secondary Outcome

Title	Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 triglycerides minus baseline triglycerides)/baseline triglycerides] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	162	43	80
Median (Full Range) [percent change]	-36.9 (34.91)	-29.6 (36.61)	-38.7 (32.31)

3. Secondary Outcome

Title	Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 HDL-C minus baseline HDL-C)/baseline HDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	162	43	80
Mean (Standard Deviation) [percent change]	13.7 (22.15)	11.2 (22.53)	5.2 (17.53)

4. Secondary Outcome

Title	Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 LDL-C minus baseline LDL-C)/baseline LDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	161	43	80
Mean (Standard Deviation) [percent change]	-19.2 (30.87)	-20.2 (22.56)	-20.5 (30.04)

5. Secondary Outcome

Title	Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 Non-HDL-C minus baseline Non-HDL-C)/baseline Non-HDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	162	43	80
Mean (Standard Deviation) [percent change]	-26.9 (26.12)	-23.8 (21.99)	-25.1 (27.83)

6. Secondary Outcome

Title	Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 VLDL-C minus baseline VLDL-C)/baseline VLDL-C] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	158	42	79
Mean (Standard Deviation) [percent change]	-33.7 (42.50)	-18.7 (58.37)	-26.6 (65.88)

7. Secondary Outcome

Title	Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study
Description	[(Week 104 Total-C minus baseline Total-C)/baseline Total-C] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time Frame	Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)

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 preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.

Arm/Group Title	ABT-335 + 20 mg Rosuvastatin	ABT-335 + 40 mg Simvastatin	ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study	Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
Measure Participants	162	43	80
Mean (Standard Deviation) [percent change]	-20.1 (21.41)	-17.9 (18.54)	-20.4 (21.57)

Adverse Events

Time Frame	Up to 116 weeks
Adverse Event Reporting Description	Anytime after initiation of combination therapy (in the preceding 12-week double-blind studies or in the preceding open-label year 1 study) to within 30 days after the last dose of combination therapy.
Arm/Group Title	ABT-335 + 20 mg Rosuvastatin		ABT-335 + 40 mg Simvastatin		ABT-335 + 40 mg Atorvastatin
Arm/Group Description	Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study		Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study		Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study
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	26/174 (14.9%)		4/50 (8%)		5/86 (5.8%)
Cardiac disorders
Coronary artery disease	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Endocrine disorders
Goitre	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Hyperparathyroidism	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Gastrointestinal disorders
Enterocele	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Lower gastrointestinal haemorrhage	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
General disorders
Chest pain	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Non-cardiac chest pain	2/174 (1.1%)		1/50 (2%)		0/86 (0%)
Hepatobiliary disorders
Cholelithiasis	0/174 (0%)		1/50 (2%)		0/86 (0%)
Infections and infestations
Diverticulitis	1/174 (0.6%)		0/50 (0%)		1/86 (1.2%)
Gastroenteritis viral	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Pneumonia pneumococcal	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Postoperative wound infection	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Subcutaneous abscess	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Injury, poisoning and procedural complications
Burns second degree	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Burns third degree	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Post procedural haemorrhage	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Postoperative fever	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Subdural haematoma	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	3/174 (1.7%)		0/50 (0%)		0/86 (0%)
intervertebral disc protrusion	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Osteoarthritis	3/174 (1.7%)		0/50 (0%)		0/86 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumour	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Colon cancer	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Lip and/or oral cavity cancer	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Lung neoplasm	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Ovarian adenoma	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Ovarian cancer	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Prostate cancer	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Nervous system disorders
Grand mal convulsion	0/174 (0%)		1/50 (2%)		0/86 (0%)
Headache	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Hydrocephalus	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Subarachnoid haemorrhage	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Syncope	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Trigeminal neuralgia	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Psychiatric disorders
Mental status changes	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
Renal and urinary disorders
Dysuria	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Haematuria	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Nephrolithiasis	0/174 (0%)		1/50 (2%)		0/86 (0%)
Reproductive system and breast disorders
Rectocele	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Uterine prolapse	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
Bullous lung disease	0/174 (0%)		1/50 (2%)		0/86 (0%)
Chronic obstructive pulmonary disease	0/174 (0%)		1/50 (2%)		0/86 (0%)
Dyspnoea	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Pneumothorax	0/174 (0%)		1/50 (2%)		0/86 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/174 (0.6%)		0/50 (0%)		0/86 (0%)
Vascular disorders
Hypotension	0/174 (0%)		0/50 (0%)		1/86 (1.2%)
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	153/174 (87.9%)		44/50 (88%)		81/86 (94.2%)
Blood and lymphatic system disorders
Anaemia	9/174 (5.2%)		0/50 (0%)		0/86 (0%)
Gastrointestinal disorders
Abdominal pain	6/174 (3.4%)		3/50 (6%)		2/86 (2.3%)
Constipation	10/174 (5.7%)		1/50 (2%)		8/86 (9.3%)
Diarrhoea	14/174 (8%)		5/50 (10%)		4/86 (4.7%)
Dyspepsia	6/174 (3.4%)		4/50 (8%)		6/86 (7%)
Gastrooesophageal reflux disease	8/174 (4.6%)		4/50 (8%)		4/86 (4.7%)
Nausea	18/174 (10.3%)		6/50 (12%)		10/86 (11.6%)
Toothache	10/174 (5.7%)		1/50 (2%)		3/86 (3.5%)
Vomiting	9/174 (5.2%)		3/50 (6%)		4/86 (4.7%)
General disorders
Chest discomfort	1/174 (0.6%)		3/50 (6%)		1/86 (1.2%)
Fatigue	12/174 (6.9%)		4/50 (8%)		5/86 (5.8%)
Oedema peripheral	2/174 (1.1%)		0/50 (0%)		7/86 (8.1%)
Pain	11/174 (6.3%)		3/50 (6%)		5/86 (5.8%)
Pyrexia	5/174 (2.9%)		0/50 (0%)		6/86 (7%)
Immune system disorders
Seasonal allergy	2/174 (1.1%)		1/50 (2%)		5/86 (5.8%)
Infections and infestations
Bronchitis	24/174 (13.8%)		8/50 (16%)		20/86 (23.3%)
Gastroenteritis	10/174 (5.7%)		3/50 (6%)		6/86 (7%)
Gastroenteritis viral	5/174 (2.9%)		1/50 (2%)		5/86 (5.8%)
Influenza	8/174 (4.6%)		4/50 (8%)		11/86 (12.8%)
Nasopharyngitis	27/174 (15.5%)		7/50 (14%)		10/86 (11.6%)
Sinusitis	24/174 (13.8%)		5/50 (10%)		10/86 (11.6%)
Upper respiratory tract infection	49/174 (28.2%)		17/50 (34%)		24/86 (27.9%)
Urinary tract infection	19/174 (10.9%)		3/50 (6%)		5/86 (5.8%)
Viral infection	3/174 (1.7%)		3/50 (6%)		3/86 (3.5%)
Injury, poisoning and procedural complications
Arthropod bite	0/174 (0%)		3/50 (6%)		0/86 (0%)
Contusion	1/174 (0.6%)		3/50 (6%)		1/86 (1.2%)
Muscle strain	5/174 (2.9%)		5/50 (10%)		3/86 (3.5%)
Investigations
Blood creatine phosphokinase increased	9/174 (5.2%)		4/50 (8%)		2/86 (2.3%)
Metabolism and nutrition disorders
Diabetes mellitus	5/174 (2.9%)		4/50 (8%)		0/86 (0%)
Type 2 diabetes mellitus	6/174 (3.4%)		3/50 (6%)		3/86 (3.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/174 (12.1%)		6/50 (12%)		14/86 (16.3%)
Back pain	31/174 (17.8%)		7/50 (14%)		15/86 (17.4%)
Bursitis	6/174 (3.4%)		3/50 (6%)		1/86 (1.2%)
Muscle spasms	11/174 (6.3%)		7/50 (14%)		10/86 (11.6%)
Musculoskeletal pain	10/174 (5.7%)		6/50 (12%)		3/86 (3.5%)
Myalgia	14/174 (8%)		4/50 (8%)		3/86 (3.5%)
Pain in extremity	18/174 (10.3%)		6/50 (12%)		10/86 (11.6%)
Nervous system disorders
Dizziness	15/174 (8.6%)		6/50 (12%)		5/86 (5.8%)
Headache	37/174 (21.3%)		12/50 (24%)		20/86 (23.3%)
Paraesthesia	7/174 (4%)		3/50 (6%)		1/86 (1.2%)
Psychiatric disorders
Depression	6/174 (3.4%)		3/50 (6%)		5/86 (5.8%)
Insomnia	16/174 (9.2%)		2/50 (4%)		6/86 (7%)
Respiratory, thoracic and mediastinal disorders
Asthma	4/174 (2.3%)		3/50 (6%)		1/86 (1.2%)
Cough	11/174 (6.3%)		4/50 (8%)		15/86 (17.4%)
Dyspnoea	1/174 (0.6%)		3/50 (6%)		2/86 (2.3%)
Nasal congestion	7/174 (4%)		4/50 (8%)		2/86 (2.3%)
Oropharyngeal pain	5/174 (2.9%)		0/50 (0%)		5/86 (5.8%)
Sinus congestion	9/174 (5.2%)		0/50 (0%)		1/86 (1.2%)
Vascular disorders
Hypertension	12/174 (6.9%)		3/50 (6%)		4/86 (4.7%)

Limitations/Caveats

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

More Information

Certain Agreements

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

Provide ABBOTT at least sixty (60) days prior to submission for review, ABBOTT shall return comments within sixty (60) days of receipt of draft. Proposed draft shall be delayed an additional sixty (60) days in addition to the Review Period.